Abstract: Autosomal dominant familial Parkinson's disease (PD) due to the alpha-synuclein (G209A) mutation shares similar clinical characteristics with sporadic PD. Pathological studies however indicate more widespread neuronal degeneration in the familial form. We performed (123)I-FP-CIT SPET (DaTSCAN) study in nine patients with familial PD carrying the alpha-synuclein (G209A) mutation and fifteen matched patients with sporadic disease. Both groups had equal radioligand reduction uptake in the striatum but the alpha-synuclein patients showed less asymmetry and increased putamen to caudate ratio. Our findings indicate that there are minor differences in DAT SPET parameters between alpha-synuclein and sporadic PD patients insufficient to provide differential diagnosis.

Abstract: BACKGROUND: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer's disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. METHODS: A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls. RESULTS: Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%. CONCLUSION: FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.

Abstract: In this article the role of molecular imaging with SPECT and PET in patients with movement disorders is reviewed. It is mentioned that SPECT and PET imaging with cocaine analogues ((123)I-beta-CIT,(123)I-FP-CIT, (18)F-DOPA), radioligands labeling the presynaptic dopamine transporters, is of value for the differentiation of patients with PD or Parkinson-plus syndromes with individuals with essential tremor. In addition the clinical impact of this procedure, the role of molecular imaging in the preclinical diagnosis and in the follow-up of patients with PD, as well as, in the differential diagnosis between Alzheimer's disease and Lewy-body dementia, is evaluated. Finally, the clinical impact of (123)I-IBZM-SPECT imaging, a radiopharmaceutical which labels the postsynaptic D(2) receptors and the discrimination between idiopathic PD and Parkinson-plus syndromes (multiple system atrophy, progressive supranuclear palsy and corticobasal ganglia degeneration), is mentioned.

Abstract: PURPOSE: Three-dimensional positron emission tomography (3D PET) results in higher system sensitivity, with an associated increase in the detection of scatter and random coincidences. The objective of this work was to compare, from a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of whole-body (WB) PET image quality with a dedicated BGO PET system.METHODS: 2D and 3D WB emission acquisitions were carried out in 70 patients. Variable acquisition parameters in terms of time of emission acquisition per axial field of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM respectively. Scatter correction was performed by convolution subtraction and a model-based scatter correction in 2D and 3D respectively. All WB images were attenuation corrected using segmented transmission scans. Images were blindly assessed by three observers for the presence of artefacts, confidence in lesion detection and overall image quality using a scoring system.RESULTS: Statistically significant differences between 2D and 3D image quality were only obtained for 3D emission acquisitions of 3 min. No statistically significant differences were observed for image artefacts or lesion detectability scores. Image quality correlated significantly with patient weight for both modes of operation. Finally, no differences were seen in image artefact scores for the different axial slice overlaps considered, suggesting the use of five slice overlaps in 3D WB acquisitions.CONCLUSION: 3D WB imaging using a dedicated BGO-based PET scanner offers similar image quality to that obtained in 2D considering similar overall times of acquisitions.

Abstract: OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Abstract: Fluorine-18 3'-deoxy-3'-fluorothymidine (18FLT) is a tissue proliferation marker which has been suggested as a new tumour-specific imaging tracer in positron emission tomography (PET). The objectives of this study were to investigate the pharmacokinetics of 18FLT in patients with colorectal cancer, defining methodologies for the quantitative analysis of the in vivo 18FLT uptake and subsequently assessing the accuracy of semi-quantitative measures. Dynamic acquisitions over a single field of view of interest identified by computed tomography were carried out for up to 60 min following injection of 18FLT (360 +/- 25 MBq). Dynamic arterial blood sampling was carried out in order to provide a blood input function. Simultaneous venous samples were also taken in order to investigate their potential utilisation in deriving a hybrid input function. Arterial and venous blood samples at 5, 15, 30, 60 and 90 min p.i. were used for metabolite analysis. Eleven patients with primary and/or metastatic colorectal cancer were studied on a lesion by lesion basis (n = 21). All acquired images were reconstructed using ordered subsets expectation maximisation and segmented attenuation correction. Time-activity curves were derived by image region of interest (ROI) analysis and image-based input functions were obtained using abdominal or thoracic aorta ROIs. Standardised uptake values (SUVs) were calculated to provide semi-quantitative indices of uptake, while non-linear regression (NLR) methodology in association with a three-compartment model and Patlak analysis were carried out to derive the net influx constant Ki. The metabolite analysis revealed two radioactive metabolites, with the parent compound representing approximately 80% of the total radioactivity in the 30-min plasma sample. In the case of NLR, better fits were obtained with a 3k model (i.e. k4 = 0) for both lesion and bone marrow time-activity curves. For the same lesions, a high correlation was observed between the Ki derived from either Patlak analysis or NLR(3k) and the corresponding SUVs. Our results also suggest that the quantitative behaviour of 18FLT in vivo (up to 60 min p.i.) may be characterised using a 3k model or Patlak analysis in combination with image-derived input functions. The good correlation found between the SUVs (at 60 min) and Ki values supports the use of semi-quantitative indices to assess the proliferation rate of colorectal cancer lesions in vivo with 18FLT.

Abstract: BACKGROUND AND AIM: Clinical governance is important. Clinical audit is part of clinical governance. The aim of this study was to perform a clinical governance exercise, and the reporting arrangements at an independent hospital provided the opportunity to do this over two phases between 1999 and 2002. Six physicians from four different UK National Health Service (NHS) trusts participated. METHODS: Reports were shown anonymously to between two and five of the physicians who had not produced the report. Reports with at least one disagreement were reviewed by the group in order to reach concensus as to whether the disagreement was non-sustainable (NS), trivial (T) or non-trivial (NT), the last two, respectively, judged to make an insignificant or potentially significant impact on patient management. RESULTS: In phase 1,239 audits were produced on 83 reports (2.9 per report), and in phase 2, 636 on 137 reports (4.6 per report). In phase 1, 14 (17%) reports attracted at least one disagreement (NS, five; T, four; NT, five). Of 239 audits, there were 20 disagreements of which five were NS. Moreover, nine audits agreed with a report with a NT disagreement, giving 14 suboptimal audits (5.9%). In phase 2, 80 (58%) reports attracted at least one disagreement (NS, 31 (P<0.003 vs phase 1); T, 35 (P<0.001); NT, 14 (P>0.05)). Of 636 audits, there were 153 disagreements, of which 37 were NS (P<0.05 vs phase 1). Twenty-five audits agreed with a report with a NT disagreement, giving 62 suboptimal audits (9.7%) (P>0.05). Overall, 19/220 reports (8.6%) were thought NT, an error rate comparable to reporting elsewhere in radiology. After phase 1, auditors became more aggressive but the quality of auditing tended to decline, as did the quality of reporting (although not significantly). CONCLUSION: This study provides a useful framework for monitoring performance.

Abstract: Hyperekplexia (HE), or startle disease, is usually a familial disorder associated with mutations in the glycine receptor alpha1 subunit gene (GLRA1), characterised by exaggerated startle reactions to unexpected auditory, somaesthetic and visual stimuli. Non-familial cases may be idiopathic, or associated with pathology usually in the brainstem or rarely in the supratentorial compartment. The pathophysiological basis of HE is unclear.We report the case of a 40-year-old woman presenting with excessive startle response to unexpected stimuli and falls since the age of 16 years. There was no family history. She was initially diagnosed with epilepsy and started on phenytoin with no resolution of her symptoms. Clinical examination revealed hyperreflexia and an insecure broad-based gait but no other abnormalities. Routine comprehensive neuropsychological assessment revealed below average intelligence with signs of frontal lobe dysfunction. EEG showed non-specific abnormalities in the right frontal and central regions. A (99m)Tc-HMPAO SPET scan revealed hypoperfusion in the frontal (worse on the right) and temporal lobes and to a lesser extent in the basal ganglia. MRI was normal, as well as blood and CSF tests. No mutations were found in a genetic analysis of GLRA1. The patient improved partially with treatment by clonazepam.The localisation of the clinical and neuropsychological findings accord with the EEG and SPET scan abnormalities in our patient and corroborates previous reports. Appropriate neuropsychological testing and functional imaging enable more accurate delineation of the clinical phenotype of this rare disorder.

Abstract: Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.

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Abstract: OBJECTIVE: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [123I]FP-CIT. METHOD: Ten neuroleptic naïve/free patients with GTS, and 10 age- and gender-matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS-related behaviours were recorded. RESULTS: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS-related behaviours. CONCLUSION: Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.

Abstract: Fluorine-18 labelled fluoro-2-deoxy- d-glucose ((18)FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [(18)F]3'-deoxy-3'-fluorothymidine ((18)FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of (18)FLT and (18)FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both (18)FDG and (18)FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours ( n=6) were visualised by both tracers, with (18)FDG showing on average twice the uptake of (18)FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with (18)FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for (18)FLT, compared with 31 (97%) for (18)FDG. No correlation was seen between the uptake of the two tracers ( R(2)=0.03). (18)FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that (18)FDG and (18)FLT image two distinct processes. The prognostic implications of the uptake of (18)FLT need to be assessed in terms of response to chemoradiotherapy and survival.

Abstract: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the common forms of dementia at post-mortem, but distinguishing between these two types of dementia is often very difficult during life. Ioflupane significantly improves the differentiation during life between DLB and AD patients. However, there is a trend for lower caudate uptake in DLB than PD and lower posterior/caudal putamen uptake in PD than in DLB. Further research is needed to test the hypothesis that dopaminergic degeneration may be different, at least regarding anatomical distribution, in DLB and PD. Furthermore, it is important to consider and discuss the potential for ioflupane in the diagnostic workup of patients with DLB.

Abstract: We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the investigation of patients with cancer. The first such unit in the UK and its mode of operation is discussed and initial applications shown. Five hundred and thirty-five patients have been scanned with 2-[18F]fluoro-2-deoxy-D-glucose from mid-January 2002 to the end of August 2002. From this initial experience a clear view of the impact of this technology is emerging. It can now be stated that (1) PET/CT does speed up the throughput of patient studies by at least 25% and hence adds to the comfort of patients scanned; and (2) PET/CT leads to greater accuracy in the interpretation of data. In view of the routine availability of high quality PET and CT fused maps a significant development in radiotherapy planning is on the horizon. We discuss our experience at present and point to further developments in the near future.

Abstract: BACKGROUND: and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). RESULTS: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4). CONCLUSIONS: (18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.

Abstract: The introduction of combined PET/CT systems has a number of advantages, including the utilisation of CT images for PET attenuation correction (AC). The potential advantage compared with existing methodology is less noisy transmission maps within shorter times of acquisition. The objective of our investigation was to assess the accuracy of CT attenuation correction (CTAC) and to study resulting bias and signal to noise ratio (SNR) in image-derived semi-quantitative uptake indices. A combined PET/CT system (GE Discovery LS) was used. Different size phantoms containing variable density components were used to assess the inherent accuracy of a bilinear transformation in the conversion of CT images to 511 keV attenuation maps. This was followed by a phantom study simulating tumour imaging conditions, with a tumour to background ratio of 5:1. An additional variable was the inclusion of contrast agent at different concentration levels. A CT scan was carried out followed by 5 min emission with 1-h and 3-min transmission frames. Clinical data were acquired in 50 patients, who had a CT scan under normal breathing conditions (CTAC(nb)) or under breath-hold with inspiration (CTAC(insp)) or expiration (CTAC(exp)), followed by a PET scan of 5 and 3 min per bed position for the emission and transmission scans respectively. Phantom and patient studies were reconstructed using segmented AC (SAC) and CTAC. In addition, measured AC (MAC) was performed for the phantom study using the 1-h transmission frame. Comparing the attenuation coefficients obtained using the CT- and the rod source-based attenuation maps, differences of 3% and <6% were recorded before and after segmentation of the measured transmission maps. Differences of up to 6% and 8% were found in the average count density (SUV(avg)) between the phantom images reconstructed with MAC and those reconstructed with CTAC and SAC respectively. In the case of CTAC, the difference increased up to 27% with the presence of contrast agent. The presence of metallic implants led to underestimation in the surrounding SUV(avg) and increasing non-uniformity in the proximity of the implant. The patient study revealed no statistically significant differences in the SUV(avg) between either CTAC(nb) or CTAC(exp) and SAC-reconstructed images. The larger differences were recorded in the lung. Both the phantom and the patient studies revealed an average increase of approximately 25% in the SNR for the CTAC-reconstructed emission images compared with the SAC-reconstructed images. In conclusion, CTAC(nb) or CTAC(exp) is a viable alternative to SAC for whole-body studies. With CTAC, careful consideration should be given to interpretation of images and use of SUVs in the presence of oral contrast and in the proximity of metallic implants.

Abstract: We tested the hypothesis that the degree of striatal dopamine D(2) receptor blockade induced by typical antipsychotic treatment directly correlates with the presence and severity of depressive symptoms in schizophrenia. Clinical and [(123)I]-IBZM single-photon emission tomography (SPET) scan data obtained from 18 typical antipsychotic treated schizophrenic patients was analysed to evaluate the relationship between striatal D(2) receptor occupancy and the depressive subscale of the Brief Psychiatric Rating Scale (BPRS-D). Striatal D(2) receptor occupancy by typical antipsychotic drugs was significantly positively correlated with BPRS-D scores (r=0.52, p=0.025). This study suggests that high striatal dopamine D(2) blockade by typical antipsychotic drugs may contribute to the emergence of depressive symptoms in typical antipsychotic treated schizophrenic patients.

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Abstract: BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.

Abstract: The application of nuclear medicine techniques to study patients with breast cancer has recently raised its profile, particularly in the investigation 'indeterminate mammographic lesions'. This review briefly points out some of the difficulties encountered with other more conventional imaging modalities and describes the radionuclide techniques most frequently employed in the investigation of those patients with breast cancer. Both planar and single photon emission tomography methods are discussed including the use of monoclonal antibodies, perfusion ligands, receptor binding hormones and other specific radiotracers, non-specific tumour markers, as well as deoxyglucose and other amino acids labelled with positron emitting radionuclides.

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Abstract: There are no large studies available to guide the selection of thallium (Tl), methoxyisobutylisonitrile (MIBI) or tetrofosmin (Tf) for myocardial perfusion imaging. Our objective was to compare the technical and clinical performance of the three in routine clinical practice. We randomised 2,560 patients to receive Tl, MIBI or Tf. A 1-day stress/rest protocol was used for MIBI and Tf. Tracer uptake was scored using a 17-segment model, quality and artefact scores were assigned, and ratios of heart (H), liver (L), subdiaphragmatic (S) and lung activity were measured. Mean quality scores (stress/rest) were Tl 2.13/2.16, MIBI 2.18/2.39, Tf 2.18/2.42 ( P=ns stress and <0.00001 rest). For attenuation artefact, Tl>MIBI=Tf ( P<0.05) and for low-count artefact Tl>MIBI>Tf ( P<0.001). For H/S, Tl>MIBI=Tf, for H/L Tl>MIBI=Tf, and for H/lung Tl<MIBI=Tf. Stress defects in the patients with reversible or mixed perfusion defects were more severe for Tl than for the other tracers (mean summed score out of 68: Tl 52.3, MIBI 55.7, Tf 54.4, P<0.01), but mean rest scores were more similar (Tl 58.7, MIBI 60.7, Tf 59.4, P=0.02). In the subset of 137 patients undergoing diagnostic perfusion studies without prior infarction, angiography or revascularisation, overall sensitivity for the detection of coronary disease defined by subsequent angiography was 91% with a specificity of 87%. There were no significant differences between the tracers with regard to sensitivity and specificity. In conclusion: There are technical differences between the tracers. Overall image quality score is superior using technetium, with less low-count artefact and less attenuation. Stress defect depth and extent are slightly greater using thallium, with no difference between MIBI and tetrofosmin. All three tracers perform well in clinical terms, with high sensitivity and specificity for angiographic stenosis and no differences in accuracy between the tracers.

Abstract: From January 2000 to April 2002 a prospective audit based on a questionnaire was carried out concerning the attitudes and viewpoints of clinicians referring patients to fluorodeoxyglucose positron emission tomography (FDG PET) scanning. A standard and structured audit form was posted to each referring doctor with the formal clinical report issued by the nuclear medicine consultant. Three hundred and thirty evaluable forms were analysed, a return rate of approximately 22%, from a total of 1500 PET patients studied during this period. FDG PET scanning was deemed by the referring physician to have altered the staging of cancer patients in 39% of all cases. Twenty-five per cent of patients were upstaged with FDG PET and 14% of patients downstaged. Patient management was changed in 39% of cases whilst a change in treatment occurred in 10% of cases. The reported FDG PET study was judged as being helpful in over 75% of all cases. These data further support evidence of the increasing role of FDG studies in the investigation of patients with cancer.

Abstract: Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared 123I-MIBG, 111In-[D-Phe1]-DTPA-octreotide and 18F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of 111In-[D-Phe1]-DTPA-octreotide and 123I-MIBG. Whole-body PET scans were performed 45 min after injection of 18F-FDG. 111In-[D-Phe1]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, 18F-FDG PET was positive in 11/15 patients and identified 107 lesions and 123I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. 18F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.

Abstract: Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.

Abstract: Standardised Uptake Values (SUVs) are widely used in positron emission tomography (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose uptake. The objective of this study was to investigate any bias introduced in the calculation of SUVs as a result of employing ordered subsets-expectation maximisation (OSEM) image reconstruction and segmented attenuation correction (SAC). Variable emission and transmission time durations were investigated. Both a phantom and a clinical evaluation of the bias were carried out. The software implemented in the GE Advance PET scanner was used. Phantom studies simulating tumour imaging conditions were performed. Since a variable count rate may influence the results obtained using OSEM, similar acquisitions were performed at total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2- and 1-min transmission datasets for the reconstruction of both phantom and patient studies. Two SUVs were estimated using the average (SUVavg) and the maximum (SUVmax) count density from regions of interest placed well inside structures of interest. The percentage bias of these SUVs compared with the values obtained using a reference image was calculated. The reference image was considered to be the one produced by filtered back-projection (FBP) image reconstruction with measured attenuation correction using the 15-min emission and transmission datasets for each phantom and patient study. A bias of 5%-20% was found for the SUVavg and SUVmax in the case of FBP with SAC using variable transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%. An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min emission dataset led to an increase in the bias of 25%-100%, with the larger increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3 and 2 min transmission may be reliably used to reduce the overall data acquisition time without compromising the accuracy of SUVs.

Abstract: Juvenile-onset dystonia that improves after levodopa may occur in both dopa-responsive dystonia (DRD) and juvenile parkinsonism (JP), clinically similar conditions with different prognoses and management goals. The authors show normal striatal uptake of the dopamine transporter ligand FP-CIT with SPECT in a clinically atypical case of DRD, in contrast to the reduced uptake observed in JP.

Abstract: BACKGROUND: The oncological applications of positron emission tomography (PET) have gained widespread acceptance. This rapidly evolving technology has been applied successfully to colorectal cancer, but has not yet become part of routine clinical practice. This review considers (1) the biological basis for the use of PET in colorectal cancer, (2) the technical aspects of PET relevant to the referring clinician and (3) the application of PET to the management of primary and recurrent disease. METHODS: A Medline database search was performed for the period 1980-2000. Experience was also drawn from the first 40 patients with colorectal cancer investigated at this institution. RESULTS AND CONCLUSION: PET has a proven role, and is cost effective in the management of recurrent cancer and the monitoring of therapy. However, further evaluation is still required to justify its routine use for other indications in colorectal cancer. Development of new positron-labelled radio- pharmaceuticals, in parallel with advances in detector technology and innovative models for tracer production and distribution, means that the availability of PET and its applications in the management of colorectal cancer will expand over the coming years.

Abstract: The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [(18)F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique.

Abstract: Positron emission tomography (PET) is now in routine use in oncology, through the success of metabolic imaging, mainly with fluorodeoxyglucose (FDG). Clear benefit is obtained with FDG PET in the assessment of patients with recurrent or residual disease, especially colorectal cancer and lymphoma. Preoperative staging of non-small-cell lung cancer with FDG PET is of proven benefit. Staging and restaging of patients with melanoma of stage II or greater is useful, and FDG PET has also been successfully used to investigate single pulmonary nodules. Tumour grading has been assessed, especially in the brain, but an important and emerging indication is the evaluation of tumour response with PET. Rapid decline of FDG uptake has been observed in responsive cancers. Further advances are being made with other fluorine-18-labelled and generator-based PET tracers, the only ones that can be used in units without dedicated cyclotrons.

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Abstract: Colorectal cancer (CRC) is the second commonest cancer in the Western World. Successful treatment relies significantly on accurate detection and staging of primary disease as well as the early identification of the presence and extent of recurrence. Morphological imaging techniques, particularly computed tomography (CT), are well established and widely available to carry out these tasks in addition to predicting and monitoring response to therapy. This review analyses the current inadequacies for imaging CRC and critically assesses the potential role of functional imaging with positron emission tomography (PET). We review the current literature, use our experience from the first 1000 PET studies carried out at our Institution and the perspective of surgical colleagues. We find little evidence for the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET for screening asymptomatic individuals and current modalities appear better suited for detection of symptomatic primary CRC. There is evidence of increased accuracy for FDG-PET in staging primary disease, but this area remains controversial and larger studies are necessary. The situation is quite the reverse with respect to imaging suspected recurrent disease with FDG-PET being more sensitive and specific than conventional techniques. This benefit manifests itself through alteration in patient management and results in cost savings. PET also appears to have a specific place in the evaluation of patients undergoing radiotherapy and chemotherapy, a role that will expand. The evidence suggests that PET will ultimately become routinely incorporated into CRC patient management algorithms. Technological advances coupled with novel tracer research will facilitate this.

Abstract: The mechanism by which vagal nerve stimulation (VNS) exerts an anticonvulsant effect in humans is unknown. This study used (99m)Tc-HMPAO single photon emission tomography (SPECT) to examine the effects of VNS on regional cerebral activity in thalamic and insular regions. Seven subjects with epilepsy who had been receiving vagal nerve stimulation for at least 6 months underwent SPECT scanning with simultaneous scalp electroencephalographic (EEG) recording. Subjects were studied in two states; during VNS activity and during a comparison condition of VNS inactivity. A region of interest analysis demonstrated that rapid cycling stimulation (7 seconds on, 12 seconds off) was associated with relatively decreased activity in left and right medial thalamic regions. No systematic stimulation-related changes were observed on visual or spectral analysis of EEG data. The thalamus is involved in modulation of ongoing cortical EEG activity in animals. Our results support the hypothesis that VNS may exert an antiepileptic action by an effect on thalamic activity.

Abstract: OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Abstract: BACKGROUND: Although alcohol dependence in women is an increasing problem, little is known about the effects of alcohol on the female brain. Evidence from a few structural and functional neuroimaging studies suggests that the female brain may be more susceptible than the male brain to the harmful effects of alcohol. However, no in vivo studies of the neuropharmacology of alcohol dependence in women have been carried out. The aim of this preliminary study was to test the hypothesis that alcohol dependence in women is associated with greater reduction in gamma-aminobutyric acid (GABA)-benzodiazepine receptor levels than in men with an equivalent drinking history. METHODS: We used single photon emission tomography and 123I-iomazenil to label the central GABA-benzodiazepine receptor and to compare semiquantified levels in 9 abstinent alcohol-dependent and 13 control women. These groups were further compared with equivalent male groups from a previous study. RESULTS: There was a trend toward a reduction in GABA-benzodiazepine receptor levels in alcohol-dependent women, but this did not reach significance. These lower levels were seen primarily in the cerebellum, occipital lobes, and parietal cortex (left > right). This was in marked contrast with the pattern of reduction seen in the previous study of male dependence, where significant reductions were seen primarily in the frontal cortex. CONCLUSIONS: Due to the semiquantitative analysis performed and the relatively small number of subjects in this study, which resulted in a nonsignificant trend, we can only comment on the differences in the pattern of lower levels of GABA-benzodiazepine receptors seen in alcohol dependence in men and women. Although we are not able to ascertain whether the female brain is more susceptible to the effects of alcohol, it appears that alcohol has a differential effect on the central GABA-benzodiazepine receptors in men and women. Recent animal evidence supports this hypothesis. Future studies should explore whether other neuropharmacological differences exist between men and women in alcohol dependence that could have implications for pharmacotherapy.

Abstract: Progress in nuclear medicine has always been a function of technological advances, and applications in neurology and psychiatry illustrate the point. Improvements in radiation detectors now allow for three-dimensional and quantitative mapping of the distribution of a labelled compound in the human brain. New ligands permit the study of specific functioning signals of the blood/brain barrier, blood flow, metabolism (oxygen, glucose, aminoacids), and neurotransmission (dopamine, benzodiazepine, serotonin receptors). The picomolar sensitivity of nuclear medicine can now be coupled to a wide group of ligands which offer specific information that can be obtained in no other way in the living patient.

Abstract: With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB). We suggest that functional imaging of the nigrostriatal dopamine pathway helps to distinguish DLB from Alzheimer's disease during life.

Abstract: Depression is a recognized feature of epilepsy. This study tested the hypothesis that depression arising in patients with epilepsy would be associated with decreased activity in brain regions previously demonstrated to be hypoperfused both in primary depression and in depression secondary to movement disorders. Two groups of patients with temporal lobe epilepsy were studied, one of which also met DSM IV criteria for a major depressive episode. All underwent a SPECT scan using the blood flow marker,(99m)Tc-HMPAO. An automated voxel-based analysis demonstrated no regions of relatively decreased activity in the depressed compared with the non-depressed patients. Sites of relative hyperactivity in the depressed group were concentrated in the left hemisphere, particularly in dorsolateral prefrontal cortex, striatum, thalamus and temporo-parietal regions. Comparison of these data with normal population data revealed that in the depressed epilepsy group regional activities were within the normal range whilst corresponding results from the non-depressed group were below it. Depressed patients with epilepsy have cerebral regions with greater perfusion than non-depressed people with epilepsy, although they are not hyperperfused compared with normals. Our results suggest that depression in people with epilepsy may arise from a mechanism which differs from that underlying the development of depression in patients with movement disorders.

Abstract: Melanin synthesised in melanoma cells presents a unique target to which the treatment can be selectively addressed, provided the pigment is recognised by a suitable drug. Methylene blue (MTB) possesses a high affinity for melanin and, therefore, accumulates preferentially in melanoma cells. Since not directly toxic to the tumour, MTB serves as a carrier for radioisotopes and, once taken up by melanoma cells, acts as a selectively localised source of radiation. Hence, radioderivatives of the compound can be used for both diagnosis and therapy of disseminated melanoma. Eleven patients with confirmed metastatic melanoma and one with a recent local recurrence were studied using radioiodinated (iodine-123 or iodine-131) MTB and a gamma camera. Biopsies of cutaneous lesions were taken to determine directly the compound uptake in tumours. This first clinical investigation concerning the diagnostic potential of radioiodinated MTB in patients with disseminated melanoma confirmed the existence of approximately 80% of internal lesions previously identified by routine methods and, additionally, enabled detection of unknown secondaries in 6 of 12 patients studied. There were no false-positive gamma camera images regardless of whether 123I or 131I was used. 131I proved to be more suitable than 123I for detecting melanoma metastases with radioiodinated MTB. Hazy images of the lesions treated with external beam radiation and/or some drugs suggest that initial radio- and chemotherapy might affect MTB uptake in melanoma metastases and reduce the clarity of the scintigrams obtained from a gamma camera. However, small, untreated internal lesions that cannot be visualised easily with the standard diagnostic methods are revealed with 131I-MTB regardless of their localisation. It is concluded that use of radioiodinated MTB in conjunction with gamma camera or positron emission tomographic imaging might prove to be a useful and accessible tool for the detection of early melanoma dissemination.

Abstract: A 68-year-old male with recurrence of malignant follicular carcinoma-oxyphilic cell type of the thyroid after surgery underwent whole body scintigraphy with 131I-sodium iodide and 99Tcm-tetrofosmin (Myoview). 131I scanning demonstrated local uptake most likely to be in the normal remnant, but 99Tcm-Myoview images delineated recurrence of the carcinoma in the neck, with more extensive involvement. We believe that a combination of 131I and 99Tcm-tetrofosmin imaging may be useful to assess the extent of disease in patients with recurrent Hürthle cell type carcinoma of the thyroid.

Abstract: BACKGROUND: We tested the hypothesis that reduced levels of the GABA-benzodiazepine receptor occur in alcohol dependency using single photon emission tomography (SPET) and the specific GABA-benzodiazepine ligand, 123I-iomazenil. METHOD: Neurologically and cognitively unimpaired abstinent alcohol-dependent (n = 12) and non-alcohol-dependent male subject (n = 14) underwent a 123I-iomazenil SPET scan. SPET and magnetic resonance images were co-registered and voxel-based statistical tests performed. Subjects' clinical and alcohol history were obtained with standard questionnaires. The relationships between clinical and alcohol variables and the regional level of GABA-benzodiazepine receptors were investigated using multiple regression analysis. RESULTS: Abstinent alcohol-dependent subjects had decreased levels of GABA-benzodiazepine receptor compared with non-alcohol-dependent subjects within the frontal, parietal and temporal cortices, including regions in which grey matter atrophy was absent. CONCLUSIONS: Alcohol dependency is associated with reduced GABA-benzodiazepine receptor levels in the absence of grey matter atrophy in some cortical regions, such as within the parietal lobe. Regional variability of reduction in GABA-benzodiazepine receptors demonstrates that alcohol does not have a global, toxic effect on the brain.

Abstract: BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

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Abstract: OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

Abstract: BACKGROUND: 5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects. METHOD: We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 123I-5-I-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM-IV schizophrenia were studied. Multi-slice SPET was performed on each subject. RESULTS: Cortex:cerebellum ratios were significantly lower in both clozapine- and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups. CONCLUSIONS: Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.

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Abstract: We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.

Abstract: OBJECTIVES: In a study of patients with focal epilepsy the hypothesis was explored that different measurements of psychopathology are related to specific distributions of cerebral perfusion. METHODS: Forty patients had SPECT performed with (99m)Tc-HMPAO. In addition, patients received a psychiatric evaluation with the following psychiatric questionnaires: the Beck depression inventory, the Leyton obsessionality inventory, the Bear-Fedio questionnaire, and the social stress and support interview. Patients were analysed in two groups according to the laterality of the epilepsy. Nine patients were excluded based on poor quality scans (n = 1), unlateralised epilepsy (n = 4), and left or ambidextrous handedness (n = 4). RESULTS: There were no overall differences between the left and right epilepsy groups on measures of psychopathology. Associations were found between scores on some of the rating scales and regional cerebral blood flow. Specifically, for patients with left sided epilepsy, higher scores on the Beck depression inventory were associated with lower contralateral temporal and bilateral frontal perfusion, and higher occipital perfusion. For patients with right sided epilepsy higher scores on the Leyton obsessionality inventory were associated with increased perfusion in ipsilateral temporal, thalamic, and basal ganglia regions and bilateral frontal regions. CONCLUSION: The results do not support the notion that lateralised epileptogenic lesions are associated with different levels of depression, obsessionality, or personality traits. They support the view that certain psychopathological symptom patterns are related to specific regional dysfunctions depending on the laterality of a hemispheric lesion.

Abstract: The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (+/-SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.

Abstract: OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.

Abstract: This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D2 receptor concentrations measured by iodine-123 iodobenzamide (123I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D2 receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand 123I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D2 receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0. 005. We can now demonstrate that the previously observed male sex-specific D2 receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D2 asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males.

Abstract: The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-io do-2-methoxybenzamide (123I-5-I-R91150 or 123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary 123I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i. ). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT2A receptors in humans (cerebral cortex>striatum>cerebellum). These findings suggest that 123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET.

Abstract: BACKGROUND: Gilles de la Tourette's syndrome (GTS) is a familial neuropsychiatric disorder characterized by tics and obsessive-compulsive behaviours (OCB). Previous HMPAO SPET studies of subjects with GTS have shown hypoperfusion of striatal and frontal areas. Studies of patients with primary obsessive-compulsive disorder have shown, in contrast, hyperperfusion of similar areas. METHODS: Twenty subjects from five families affected by GTS, including individuals with OCB but no tics, were examined using HMPAO SPET. RESULTS: There were abnormalities of regional cerebral perfusion in individuals with GTS, OCB and tics. Hypoperfusion was in striatal, frontal and temporal areas. There was no hyperperfusion. CONCLUSIONS: Regional cerebral blood flow patterns in individuals with OCB in families affected by GTS are comparable to their relatives with GTS and differ from individuals with primary OCD in the absence of a family history of tic disorders.

Abstract: Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty by neuropathological examination. Diagnosis during life remains at best probable, based on the presence of symptoms known from autopsy studies to be frequently associated with DLB. The greatest practical clinical problem lies in distinguishing DLB and Alzheimer's disease (AD). In DLB there is a considerable degeneration of nigral neurones with depletion of striatal dopamine. In contrast, AD is not associated with significant changes in dopamine metabolism. Iodine-123 iodobenzamide single-photon emission tomography (IBZM-SPET) measures post-synaptic dopamine D2 neuroreceptor availability in the corpus striatum, but is nevertheless a method for assessing the integrity of the nigrostriatal dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal controls and 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5-2 h after intravenous injection of 185 MBq of 123I-IBZM. Circular regions of interest were employed to calculate radioactivity ratios in each hemisphere as follows: caudate nucleus/frontal cortex, putamen/frontal cortex and caudate nucleus/putamen. The DLB patients had significantly lower left caudate/putamen ratios (95% confidence intervals: DLB 0.893-0.965, AD 0.972-1.175, controls 1.031-1.168) than either controls or AD patients, and significantly lower right caudate/putamen ratios (95% confidence intervals: DLB 0.926-1.019, AD 0.954-1.103, controls 1. 027-1.144) than controls. Our data suggest that patients with DLB diagnosed by clinical criteria have changes in striatal post-synaptic D2 receptors. This may be of value in distinguishing DLB from AD during life.

Abstract: We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD.

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Abstract: BACKGROUND: We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM-III-R anxiety disorders. METHOD: Fifteen patients with obsessive -compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET. RESULTS: MANOVA revealed significant rCBF differences between diagnostic groups (F = 4.4; d.f. = 3, 57; P = 0.007) and between cerebral regions (F = 6.4; d.f. = 1, 57; P = 0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r = 0.24, n = 46, P = 0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r = -0.24, n = 46, P = 0.05) and right caudate rCBF (r = -0.31, n = 46, P = 0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r = -0.49, n = 16, P = 0.03) and with right caudate rCBF (r = -0.7, n = 16, P = 0.001). CONCLUSIONS: Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.

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Abstract: PURPOSE: To determine the prevalence of MR white matter abnormalities in patients with chronic fatigue syndrome (CFS). METHODS: Brain MR studies of 43 patients (29 women and 14 men, 22 to 78 years old) with a clinical diagnosis of CFS (n = 15), CFS with associated depression (n = 14), and CFS with associated other psychiatric disorders, namely, anxiety and somatization disorder (n = 14), were compared with brain MR studies in 43 age- and sex-matched control subjects. RESULTS: MR findings were abnormal in 13 (32%) of the patients in the study group (ages 34 to 78 years) and in 12 (28%) of the control subjects (ages 26 to 73 years). One patient with CFS had multiple areas of demyelination in the supratentorial periventricular white matter. Another patient with CFS and associated depression had a single focus of probable demyelination in the supratentorial periventricular white matter. In four patients with CFS (ages 34 to 48 years) MR abnormalities consisted of one or several punctate hyperintense foci in the corona radiata, centrum ovale, and frontal white matter. The remaining seven patients (ages 50 to 78 years) had frontoparietal subcortical white matter foci of high T2 signal. The prevalence of white matter hyperintensities was not different between the patients and the control subjects. CONCLUSIONS: Our findings suggest that no MR pattern of white matter abnormalities is specific to CFS.

Abstract: A 33-yr-old homosexual man with acquired immune deficiency syndrome (AIDS) and Mycobacterium avium intracellulare (MAI) infection presented with fever, sweats, lethargy and dyspnea. A chest radiograph showed cardiomegaly and an echocardiograph revealed a large pericardial effusion. After pericardial aspiration, which confirmed T cell non-Hodgkin's lymphoma, he remained dyspneic. Gallium-67 imaging was performed to determine whether the patient's residual dyspnea was related to pulmonary MAI infection or lymphomatous infiltration of the heart. Planar 67Ga scintigraphy revealed intense tracer uptake in two areas within the mediastinum and surrounding the entire heart shadow but no evidence of pulmonary MAI infection. SPECT 67Ga scintigraphy precisely localized the two mediastinal abnormalities and demonstrated the tracer uptake around the heart to be pericardial rather than myocardial. Gallium-67 scintigraphy suggested that pericardial lymphoma was the likely basis of the patient's dyspnea.

Abstract: Using single photon emission computerized tomography (SPECT), we demonstrated that in patient A, a 20-year-old male with polycythaemia, the cerebral blood flow was decreased (presumably as a result of increased viscosity and or microemboli), probably leading to frightening visual distortions (dysmorphopsia) associated with scintillating specks of bright colors (Teichopsia). This had presumably precipitated agoraphobia. After hospitalization, when the patient had not responded to efforts at systematic desensitization, he improved through a combination of multiple venesections and antiplatelet aggregation therapy (aspirin 75 mg o.d.) over 3 months combined with systematic desensitization. A subsequent SPECT demonstrated an increase in cerebral blood flow to normal levels, which coincided with improvement of agoraphobic symptoms and disappearance of visual distortions on further follow-up. This paper depicts another yet undocumented example of an alarming physical symptom probably leading to a cognitively-based panic sufficient to cause agoraphobia by classical conditioning. It also suggests that prior treatment of such physical symptoms is likely to facilitate the process of systematic desensitization.

Abstract: Targeted radiotherapy for pigmented melanoma with 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with Astatine-211 (211At; alpha-particle emitter) proved to be very effective in animal model systems. Since the results justified an introduction of the treatment to the clinic, the aim of the bio-distribution studies using [123I]-MTB and [131I]-MTB in patients was to confirm selectiveness of radiolabelled MTB uptake in melanoma lesions. The investigations were carried out using planar and SPECT (single photon emission computed tomography) gamma-cameras. A stable uptake of radioiodinated MTB was found in pigmented melanomas in man, with tumour/surrounding tissue and tumour/blood ratios amounting to 9 at 19 h after a single i.v. injection. A time-dependent kinetics of radioiodinated MTB distribution was similar to that observed in human melanoma-bearing athymic mice. Blood radioactivity decreased by about 90% during the first 2.5 min after i.v. injection of the compound (T1/2biol = 0.58 min). Its retention time in various organs was either the same or very similar to that characteristic of the blood. A rapid uptake of radioiodinated MTB in the liver and kidneys confirmed the importance of these organs in excreting the compound: 25-30% of the radioactivity administered was expelled with urine over the first 24 h after the injection. There was no obvious retention of radioiodinated MTB in the brain over the observation period and in the eyes for at least the first 14 h.

Abstract: BACKGROUND: Chronically dysfunctional myocardium may improve after coronary revascularization. This condition was thought to be due to a chronically reduced myocardial blood flow (MBF). Recently, however, it has been shown that in patients without previous infarction but with chronic left ventricular dysfunction, baseline MBF was normal. METHODS AND RESULTS: To study the pathophysiology of chronic left ventricular dysfunction in patients with previous infarction, regional MBF (milliliter per minute per gram of water-perfusable tissue) and glucose utilization (MRG; micromoles per minute per gram) during hyperinsulinemic euglycemic clamp were measured with positron emission tomography in 30 patients before bypass. At baseline, 133 myocardial segments were normal, and 107 were dysfunctional. After revascularization, 59 of 107 segments improved, while 48 of 107 were unchanged. MBF was 0.92 +/- 0.25 mL.min-1.g-1 in normal segments, 0.87 +/- 0.31 mL.min-1.g-1 in improved segments (P = NS versus normal), and 0.82 +/- 0.40 mL.min-1.g-1 in unchanged segments (P < .05 versus normal). In 90% of the dysfunctional segments, MBF was > 0.42 mL.min-1.g-1, a cutoff value corresponding to the mean MBF minus 2 SD in normal segments. The MRG was 0.71 +/- 0.14 mumol.min-1.g-1 in 9 age-matched normal subjects, 0.45 +/- 0.19 mumol.min-1.g-1 (P < .01) in normal segments, 0.44 +/- 0.14 mumol.min-1.g-1 in improved segments (P = NS versus normal), and 0.34 +/- 0.17 mumol.min-1.g-1 in unchanged segments (P < .01 versus normal and improved). CONCLUSIONS: The results suggest that resting MBF measured with 15O-labeled water in chronically dysfunctional segments is not reduced and that the myocardium of these patients is less sensitive to insulin than that of normal subjects.

Abstract: We have studied striatal D2 dopamine binding in schizophrenic patients treated with the novel atypical antipsychotic drug, olanzapine. 123I iodobenzamide (IBZM) single photon emission tomography (SPET) was used to estimate striatal dopamine D2 receptor binding in vivo. Patients were recruited from a prospective, double blind controlled trial of olanzapine versus haloperidol treatment. In vivo striatal D2 binding data from olanzapine treated patients (n = 6) were compared with previously reported data from typical antipsychotic responsive (n = 10); clozapine (n = 10); and risperidone (n = 6) treated patient groups. Mean % Brief Psychiatric Rating Scale score (BPRS) improvement following olanzapine treatment was 49% (SD 44). The hypothesis that clinical improvement in olanzapine treated patients would be associated with higher mean striatal D2 binding of 123I IBZM (reflecting lower levels of D2 occupancy) than typical antipsychotic (1.25 +/- 0.05) or risperidone (1.24 +/- 0.04) treatment was confirmed. Olanzapine treated patients had similar levels of striatal D2 binding in vivo (1.41 +/- 0.06) as those treated with clozapine (1.49 +/- 0.04). This preliminary evidence suggests olanzapine is another atypical antipsychotic drug in which therapeutic response is not associated with a high degree of striatal D2 receptor occupancy in vivo.

Abstract: To date cardiac positron emission tomography (PET) studies have focussed on the measurement of myocardial blood flow, metabolism and receptors while left ventricular (LV) function and dimensions have been derived from other modalities. The main drawback of this approach is the difficulty of data co-registration, which limits clinical interpretation. The aim of this study was to evaluate whether it is possible to measure absolute cardiac volumes, and consequently LV function parameters such as ejection fraction, and wall motion with gated PET. Nineteen patients underwent a PET scan and planar radionuclide ventriculography (MUGA) within 9+/-9 days. A 9-min scan (16 gates/cardiac cycle) was acquired after inhalation of 3 MBq/ml of oxygen-15 labelled carbon monoxide at the rate of 500 ml/min over 4 min using a multislice PET camera. Noise reduction was performed on the gated image to enhance the definition of the ventricles before reslicing to the short-axis view. A threshold value was used to detect the edge of the LV at each gate. LV volumes at each gate were estimated by summing the volume of voxels within the LV boundary. PET measurements of LV volumes were as follows: LV end-diastolic volume ranged from 72 to 233 ml and LV end-systolic volume ranged from 24 to 203 ml. Phantom experiments supported the validity of this approach for estimating volumes. LV ejection fraction measured with MUGA was 38.4%+/-16.3% (range 15%-71%) and that measured with PET was 39.6%+/-17.7% (range 9%-72%) (P=NS). The LV ejection fraction measurements were highly correlated (r2=0.824). These results indicate that: (1) absolute end-diastolic and end-systolic volumes can be quantified using gated PET and (2) LV ejection fraction can be accurately measured by gated PET simultaneously with the other physiological PET parameters.

Abstract:

Abstract: The early identification of renal cortical scarring secondary to urinary reflux and/or renal infection is important in the management of patients with recurrent disease. Scintigraphic imaging of the renal cortex using 99Tcm-dimercaptosuccinic acid (DMSA) is often considered the standard method for the diagnosis of renal scars in both adults and children. Consistent reporting of 99Tcm-DMSA is nevertheless essential in ensuring that the clinician can act on the data reported. In this study, seven experienced observers were asked to report, independently, 99Tcm-DMSA data sets from 32 patients. The observers were asked to note the presence of a space occupying lesion or of a renal cortical scar(s) and to conclude if the kidney was normal or abnormal. There was marked variation in the number of renal cortical scars reported, the total number of scars seen and whether or not the kidney was normal or abnormal. After peer review of all data, consensus and referenced criteria were arrived at for a reanalysis of data. All scans were reread by the observers. There was some improvement in the concordant reporting of kidneys with renal scars (51 vs 61%) and whether or not the kidney was normal or abnormal (53 vs 63%). However, this was not statistically significant (at a level of P < 0.05). This study demonstrated significant inter-observer variation regarding the reporting of 99Tcm-DMSA studies. A consensus with agreed guidelines for data interpretation did not significantly affect this apparent lack of consistency of reporting.

Abstract: The prognostic value of myocardial perfusion scintigraphy is beginning to be recognised in patients undergoing cardiovascular surgery. The aim of this prospective study was to assess the predictive value of scintigraphy in elderly patients undergoing major non-vascular abdominal surgery. Adenosine stress thallium-201 (201Tl) single-photon emission tomography (SPET) was employed for imaging using a standard protocol. Patients over the age of 60 years (n = 55) with an intermediate to high likelihood of coronary artery disease were evaluated prospectively. The clinical outcome variables analysed were cardiac mortality and major cardiac morbidity occurring within 30 days of surgery. Cardiac events were cardiac death (n = 5), angina pectoris (n = 5), nonfatal mycardial infarction (n = 1), acute left ventricular failure (n = 2) and arrhythmias requiring treatment (n = 4). All cardiac events occurred in the first 10 postoperative days except one cardiac death which happened on the 29th postoperative day. Patients with an abnormal 201Tl SPET scan had a higher risk of postoperative death (4 vs 1) or any postoperative cardiac event (13 patients vs 4 patients; P < 0.0001) when compared with those with a normal scan. The sensitivity, specificity and positive predictive value of 201Tl imaging for perioperative ischaemia and adverse outcomes were 76%, 82% and 65%, respectively. The occurrence of an intraoperative event (P < 0.02) and the length of surgery (P < 0.01) were also predictors of a postoperative cardiac event. Clinical risk variables and an abnormal electrocardiogram in isolation were poor predictors. In conclusion, preoperative myocardial perfusion scintigraphy is a valuable technique for identifying elderly patients with a high risk for cardiac events when undergoing major non-vascular abdominal surgery.

Abstract: The diagnosis of non-epileptic seizures (NES) is problematic. Although diagnosis can be achieved by videotelemetry, these facilities are expensive and not widely available. HMPAO SPECT studies show focal hypoperfusion interictally in focal epilepsy. SPECT has not been studied in any detail in NES previously. Two groups (10 patients each) were studied, one with NES and one with complex partial seizures and localisation related epilepsy. SPECT scans were normal in 7 of 10 (70%) NES patients, while showing clear focal hypoperfusion in 8 of 10 patients (80%) with epilepsy. In the NES group, 1 patient showed hypoperfusion indistinguishable from that seen in epilepsy, while 2 patients in the epilepsy group showed only equivocal focal hypoperfusion. The remaining 2 patients in the NES group showed bifrontal and equivocal focal hypoperfusion. A normal HMPAO SPECT study supports the diagnosis of NES in patients with seizures of uncertain aetiology.

Abstract: A recent survey of the knowledge and practice of both positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) of the brain among referring physicians in Europe (neurologists and psychiatrists) showed a disquieting lack of knowledge of the potential of these methodologies in the investigation and management of patients of their own specialities. The need to bring the knowledge of the potential of these techniques to the practicing physicians is paramount. It is imperative that the methodologies and concepts that preside over the application of these techniques in neurology and psychiatry must become more uniform if an impact is to be felt at a clinical level. There is clear improvement in the instrumentation available with the new state-of-the-art tomographic devices and with the development of new technetium-based radiopharmaceuticals for the study of cerebral perfusion. The constant progress made with ligands that permit the study of neurotransmission, tumor metabolism, and turnover do expand our capability to improve the knowledge concerning neurophysiology, neuropathology, and neuropharmacology of a variety of disease states. PET and SPECT will be progressively included in protocols aimed at stratifying patients with dementia, monitoring therapeutic trials, and improving our ability to determine outcome. Clinical usefulness of PET and SPECT begin to emerge in cerebral vascular disease, in the identification of cerebral death, in epilepsy, in cerebral trauma, in the investigation of HIV-positive patients with cerebral involvement, and in the monitoring of tumor recurrence and postirradiation damage. This review article outlines a current perspective of SPECT and PET as practiced in Europe, its potential, and its limitations.

Abstract: Interictal blood flow single photon emission computed tomography (SPECT) has been considered to be of limited value in the investigation of patients with partial epilepsies. Newer SPECT technologies using brain dedicated multiple detector systems have not been fully evaluated. To study the usefulness of an optimized SPECT technique, we scanned 40 epilepsy patients and ten normal subjects. Interictal [99mTc]hexamethylpropylene amine oxime (HMPAO) SPECT scans were acquired using the GE/CGR Neurocam triple-headed brain-dedicated system. The results of a qualitative analysis of the scans were compared to EEG and optimised MRI findings. Eight of the normal subjects and one of 40 patients had normal SPECT scans. There was a comparable concordance of lateralization between SPECT, MRI and EEG. The majority of our patients had mesial temporal pathology on MRI. Perfusion abnormalities extending beyond the mesial temporal area were common and did not simply relate to structural abnormalities. Quantification of blood flow in multiple brain regions revealed that hypoperfusion did not occur at random. Perfusion in the mesial temporal lobe was related to perfusion in anatomically and functionally related ipsilateral and contralateral brain regions. These hypoperfused areas probably reflect dysfunctioning areas which are related to the epileptogenic process.

Abstract: Corticobasal degeneration (CBD) is a rare syndrome characterised by an asymmetrical rigidity with localised cortical signs, particularly apraxia. Using positron emission tomography, abnormal patterns of cortical metabolism have recently been shown. We have studied patterns of regional cerebral blood flow (rCBF) using single photon emission tomography, with the tracer 99Technetium hexamethylpropylenamine (HMPAO), in subjects with CBD. In subjects with CBD, compared with 12 age-matched normal controls, in the clinically more affected hemisphere a characteristic pattern was found with significant reductions in HMPAO uptake in the posterior frontal cortex (by 11.5%), and in the superior, inferior, anterior, and posterior parietal cortex (by 12.2, 12.9, 12.9, and 9.7, respectively). Reduced uptake was also found in the caudate (9.3%), putamen (9.7%), and thalamus (8.6%). In contrast, HMPAO uptake in the temporal and occipital cortex was normal. In comparison with 12 Parkinson's disease (PD) controls, significant reduced uptake was seen in the thalamus (9.0%), posterior frontal (8.9%), and inferior (9.9%), and anterior parietal (9.5%) cortex. A similar pattern of impaired uptake was seen in the clinically less/unaffected cerebral hemisphere in patients with CBD compared with normal controls, with a significant reduction in HMPAO uptake in the thalamus (6.8%), superior parietal (9.6%) and anterior parietal (7.6%), and posterior parietal (7.3%) cortex. This implies that the disease process is bilateral even in those cases with clinically unilateral disease. This widely available technique may be useful in the early diagnosis of CBD and in differentiation from other extrapyramidal disorders.

Abstract: Risperidone and remoxipride are recently introduced atypical antipsychotics, with clinical efficacy comparable to that of classical antipsychotics but lower propensity to induce extrapyramidal side effects (EPS). It is unclear whether these properties relate to weak dopamine D2 receptor blockade in vivo, as has been suggested for the archetypal atypical antipsychotic clozapine. We have used 123I-IBZM single photon emission tomography (SPET) to characterize the patterns of striatal D2 receptor binding in vivo in DSMIII-R-diagnosed schizophrenic and schizo-affective patients treated with either risperidone (n = 6) or remoxipride (n = 4) but predominantly EPS free. These groups were compared to age- and BPRS- matched subjects from a previously reported D2 receptor binding database of patients treated with clozapine (n = 10) and classical antipsychotics (n = 10). Patients on risperidone and remoxipride had high levels of D2 receptor blockade, comparable to those of patients on classical antipsychotics, and significantly greater than those obtained with clozapine-treated patients (risperidone versus clozapine, P < 0.005; remoxipride versus clozapine, P < 0.025). These results suggest high levels of striatal D2 receptor occupancy in association with remoxipride and risperidone treatment and argue against modest D2 antagonism as the explanation for the low incidence of EPS associated with these drugs.

Abstract: Technetium-99m tetrofosmin is a recently developed compound that clears from background organs rapidly. Tetrofosmin has a good correlation with 201Tl. This study assesses the feasibility and diagnostic accuracy of a combined protocol involving rest 201Tl SPECT and stress imaging with 99mTc-tetrofosmin. METHODS: Twenty-five patients (23 men, 2 women; aged 36-73 yr) with known coronary artery disease underwent the combined protocol. Twenty minutes after the resting injection of 201Tl, resting SPECT data were acquired using low-energy, high-resolution collimators. A stress test using adenosine infusion combined with low-level dynamic exercise was performed. The stress data were collected 20 min later. The reconstructed vertical long-axis, horizontal long-axis and short-axis slices were analyzed qualitatively. Analysis was carried out using nine segments of the left ventricle. The segments were reported either as fixed or reversible. The results were compared to coronary angiography results. RESULTS: The sensitivity and specificity for the detection of diseased coronary vessels were 85% and 70% for the left anterior descending territory, respectively, 78% and 71% for the right coronary artery, and 69% and 70% for the left circumflex. Overall, the sensitivity was 80% and the specificity 70%. CONCLUSION: Combined rest 201Tl/stress 99mTc-tetrofosmin SPECT provides a protocol of short duration which displays similar diagnostic accuracy to a protocol using tetrofosmin as a single agent.

Abstract: Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABAA receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8 +/- 3.9 years). The patterns obtained were largely compatible with the known distribution of GABAA receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest 123I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific 123I-iomazenil binding in neocortical and cerebellar regions from 60-75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume 123I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia.

Abstract: BACKGROUND. Functional brain imaging with technetium-99m d,l-hexamethyl propyleneamine oxime (HMPAO) Single Photon Emission Tomography (SPET) allows us to explore the cerebral pathophysiology of Gilles de la Tourette's Syndrome (GTS). METHOD. Fifty patients and 20 controls were examined. Patients were rated for tic severity and mood. Scans were analysed quantitatively using internal ratios to the occipital cortex. RESULTS. Patients different from controls on measures of relative blood flow to the left caudate, anterior cingulate cortex and the left dorsolateral prefrontal cortex. Severity of tics was related to hypoperfusion of the left caudate and cingulate and a left medial temporal region. Hypoperfusion in the left dorsolateral prefrontal region was related to mood. CONCLUSIONS. The areas found to be hypoperfused in this study are consistent with known functions of fronto-striatal circuits. A wide range of perfusion patterns is seen, however, and no characteristic patterns for behavioural subgroups has been documented with this technique.

Abstract: BACKGROUND. We tested whether cortical and subcortical regional cerebral blood flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and healthy controls. We then explored the relationship between rCBF and OCD mental state. METHOD. Thirty out-patients from the Maudsley Hospital with OCD as defined in DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions of interest and compared with rCBF data in 30 healthy people matched for age, sex and handedness. Symptom ratings were obtained using standard measures on the scanning day. Principal components factor analysis identified two distinct clinical dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These were correlated with patients' rCBF measurements, using Spearman's rank correlation coefficient, and multiple regression coefficients calculated. RESULTS. We found significant reductions in rCBF measurements of OCD patients compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal cortex, right caudate nucleus and right thalamus. Regional differences were not secondary to generalised reduction in patients' brain perfusion. Reduced blood flow to the right inferior frontal cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset, sex, handedness, depression or medication status. OC clinical dimension, concerning obsessions, compulsions and low mood, was significantly negatively correlated with left inferior frontal, medial frontal and right parietal rCBF. AA dimension, concerning anxiety and avoidance, was significantly positively associated with left and right superior frontal, right inferior frontal, medial frontal cortical, and right and left caudate and thalamic rCBF. CONCLUSIONS. rCBF differs significantly between resting OCD patients and healthy controls, and separate clinical dimensions are associated with functionally distinct rCBF patterns.

Abstract: Single photon emission tomography with split-dose technetium-99m-d, l-hexamethyl-propylene amine oxime was used to measure regional cerebral blood flow (rCBF) during a memory-activation paradigm in a group of 18 medicated DSM-III-R schizophrenic patients. The relationship between clinical features of schizophrenia and rCBF patterns was examined. Increased blood flow to the left basal ganglia was revealed during activation in patients reporting hallucinations in the previous month, a finding that was not influenced by medication dose or other confounding variables. This result adds to previous functional imaging studies that have related basal ganglia abnormalities to hallucinatory phenomena and suggests that left basal ganglia hyperactivity may be relevant to an internal monitoring deficit responsible for the appearance of those symptoms in schizophrenia.

Abstract: Technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC), a new renal imaging agent, was introduced as an alternative to 99mTc-mercaptoacetyltriglycine (MAG3). This radiopharmaceutical can be easily labelled at room temperature and has high radiochemical purity and long stability. The aim of this study was to gain clinical experience in using 99mTc-L,L-EC in normal volunteers and patients. The clearance of this radiopharmaceutical was compared with that of iodine-131 ortho-iodohippurate (OIH) in five healthy volunteers. In addition, conventional renogram and whole-body distribution of 99mTc-L,L-EC (40 min and 3 h post-injection) were evaluated in these subjects. Subsequently, ten patients with suspected obstructive nephropathy, four with renovascular disorders and two in acute renal failure were imaged. In five patients with impaired renal function both 99mTc-MAG3 and 99mTc-L,L-EC studies were performed. In each case the scintigraphic images and time/activity curves were evaluated and various semiquantitative parameters calculated and compared. No adverse effects were noted during and after 99mTc-L,L-EC scintigraphy. The mean clearance values for 99mTc-L,L-EC and 131I-OIH in volunteers were 504 and 663 ml/min respectively. The total plasma clearance of 99mTc-L,L-EC was about 75.8% of the 131I-OIH value. In volunteers the parenchymal transit time index, whole kidney transit time index and mean parenchymal transit time for 99mTc-L,L-EC were 63 s, 124 s and 175 s respectively. The mean time to peak activity was 235 s and the time from peak to 50% of peak activity was 402 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: We looked for brain perfusion abnormalities in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study revealed widespread reduction of regional brain perfusion in 24 ME/CFS patients, compared with 24 normal volunteers. Hypoperfusion of the brainstem (0.72 +/- 0.05 vs. 0.80 +/- 0.04, p < 0.0001) was marked and constant. We then tested whether perfusion to the brainstem in ME/CFS patients differs from that in normals, patients with major depression, and others with epilepsy. Data from a total of 146 subjects were included in the present study: 40 normal volunteers, 67 patients with ME/CFS (24 in the pilot study, 16 with no psychiatric disorders, 13 with ME/CFS and depression, 14 with ME/CFS and other psychiatric disorders), 10 epileptics, 20 young depressed patients and 9 elderly depressed individuals. Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) and single-photon emission tomography (SPET) with a dedicated three-detector gamma camera computer/system (GE Neurocam). Brain-stem hypoperfusion was confirmed in all ME/CFS patients. Furthermore, the 16 ME/CFS patients with no psychiatric disorders and the initial 24 patients in the pilot study showed significantly lower brainstem perfusion (0.71 +/- 0.03) than did depressed patients (0.77 +/- 0.03; ANOVA, p < 0.0001). Patients with ME/CFS have a generalized reduction of brain perfusion, with a particular pattern of hypoperfusion of the brainstem.

Abstract: The value of immunoscintigraphy with technetium-99m (99Tcm) labelled anti-granulocyte monoclonal antibody (BW250/183) was studied prospectively in human immunodeficiency virus (HIV-1) antibody-positive patients presenting with fever without localizing symptoms or signs. Twenty-three studies were performed in 23 patients and the results of 99Tcm-anti-granulocyte imaging were compared with the definitive microbiological or cytological diagnosis. Twenty-one patients had an infective cause of pyrexia, one patient had disseminated lymphoma and one Kaposi sarcoma. 99Tcm-anti-granulocyte antibody imaging correctly identified the sites of infection in only five (24%) patients, four of whom had infective colitis (one also had bacterial pneumonia) and one of whom had cellulitis. Sixteen foci of infection were not localized by 99Tcm-anti-granulocyte immunoscintigraphy (false-negative scans). Six of these patients had Pneumocystis carinii pneumonia; other diagnoses in this group included bacterial or fungal pneumonia and bacteraemia secondary to line infections. 99Tcm-anti-granulocyte antibody did not accumulate in the patients with disseminated lymphoma and Kaposi sarcoma (true-negative scans). 99Tcm-anti-granulocyte imaging, therefore, appears useful in identifying extrathoracic infection in HIV-1 positive patients. Its lack of sensitivity for the identification of pulmonary infection means that its role in the investigation of HIV-1 antibody-positive patients with fever without localizing symptoms or signs is limited.

Abstract: Infection with the human immunodeficiency virus-type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the acquired immunodeficiency syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin's B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). In this manuscript we review the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion single photon emission tomography (SPET), neuroreceptor and positron emission tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumor markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with 201Tl using quantification (tumour to nontumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.

Abstract: In order to study the nature of dopaminergic activity in epileptic psychoses we investigated striatal dopamine receptor binding in 14 patients with epilepsy. Seven of the patients were acutely psychotic when studied, having recently developed a periictal schizophreniform psychosis. The remaining patients were not psychotic. All patients were scanned using single photon emission tomography (SPET) with 123I-IBZM, a specific dopamine D2 receptor ligand. A region of interest analysis was performed. Comparison of mean basal ganglia to occipital cortex activity ratios in the two groups demonstrated significantly reduced specific binding of 123I-IBZM to striatal D2 receptors in the psychotic patients compared to those without psychosis.

Abstract: Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.

Abstract: Animal models suggest a relationship between disturbed striatal dopaminergic function and stereotyped behaviour. Several studies show increased stereotypy in schizophrenic patients compared to normal controls. We investigated the performance of 12 antipsychotic-drug-free schizophrenic patients, and 15 healthy control subjects on a neuropsychological measure of stereotypy--the two-choice guessing task--and correlated this with in vivo striatal dopamine D2 receptor binding, as measured by 123I-iodobenzamide single photon emission tomography. Patients and controls did not differ with respect to the measures of stereotypy derived from the task. However, there was a significant correlation between one of these measures (RR Information) and the degree of striatal D2 receptor binding asymmetry in the patient group only. In view of research connecting striatal and frontal lesions with stereotypy in animals and cognitive inflexibility in humans, these data could suggest a similar disturbance underlying the phenomenon in schizophrenia.

Abstract: We used SPECT to examine striatal D2 receptor binding in 20 antipsychotic-free DSM-III-R schizophrenic patients and 20 age- and sex-matched normal controls. Dynamic single-slice SPECT, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq of 123I-IBZM. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. There was no overall elevation of D2 receptor binding between patients and controls. A male sex-specific left lateralised asymmetry of striatal D2 receptor binding was found in the patient group. Age-dependent decline of striatal D2 receptors was confirmed in controls, but not in patients. These results suggest that alterations in striatal D2 receptor distribution and density do occur in schizophrenia, and possibly reflect wider disruptions in prefrontal-striatal-limbic circuits.

Abstract:

Abstract: Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophrenic patients and age, sex and handedness matched normal volunteers using a split-dose 99mTc-HMPAO Single Photon Emission Tomography (SPET) protocol. Measures were taken during the performance of a verbal memory task aimed at activating the left medial temporal lobe, a region repeatedly suggested to be structurally abnormal in schizophrenia. In normal subjects, the performance of the task was associated with significant rCBF increases in the left medial temporal, left inferior frontal and anterior cingulate cortices, and right cerebellum. Despite their significantly poorer performance on the memory task, the degree of medial temporal activation measured in the schizophrenic patients was not significantly different from that found in the control group. This finding suggests that memory deficits in schizophrenia do not necessarily imply failure to activate the left medial temporal lobe as assessed by 99mTc-HMPAO SPET.

Abstract: A large body of evidence suggests that abnormal dopaminergic activity is present in Gilles de la Tourette Syndrome (GTS). To investigate whether dopamine dysregulation involving the D2/D3 receptor occurs in GTS, we performed single slice dynamic single photon emission computed tomography (SPECT) with 123iodo-6-methoxybenzamide (123I-IBZM) in 15 GTS patients (eight unmedicated) and six healthy volunteers. After intravenous administration of 5 mCi (185 MBq) of 123I-IBZM, dynamic SPECT (5 minutes per slice) studies were performed at the level of the basal ganglia for 55 minutes. The mean activity per pixel in the basal ganglia was compared with the mean activity per pixel in the visual cortex. Unmediated GTS patients showed no differences from control subjects. However, GTS patients taking D2 blocking medications had significantly decreased 123I-IBZM binding compared with control subjects in both the right and left basal ganglia. Thus, D2/D3 receptor availability, as measured by 123I-IBZM SPECT, is not abnormal in GTS.

Abstract: The clinical experience with the Toshiba GCA-9300A single photon emission tomography (SPET) system is discussed along with typical acquisition protocols for various SPET studies. The system was used to perform SPET studies in normals and in a variety of brain and body disorders. Its three Anger-type gamma cameras forming a triangular aperture offer a substantial increase in sensitivity compared to a single rotating gamma camera. This has allowed the routine use of lead fanbeam super high-resolution collimators (SHR FB) for 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain SPET studies and high-resolution parallel-hole collimators (HR PH) for cardiac and other body studies. The resulting improvement in spatial resolution coupled with the ease of patient positioning and the greater patient throughput compared to a conventional tomographic gamma camera, will enhance the role of brain and body SPET for both routine and research purposes.

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Abstract: Relative regional cerebral blood flow (rCBF) was measured at rest and during a verbal fluency task in ten elderly patients with major depressive disorder and nine controls. At rest, depressed patients showed significant reductions in the cortico-cerebellar ratios of tracer uptake in the right and left parietal, left temporal and left occipital regions. During the task relative rCBF increased in patients such that these differences disappeared. Relative rCBF did not correlate with severity of depressed mood or endogenous features but did correlate positively with severity of psychotic symptoms. Frontal relative rCBF correlated negatively with somatic symptoms and anxiety.

Abstract: The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.

Abstract: Single photon emission computed tomography (SPECT) with the tracer 99Tcm-hexamethylpropyleneamine oxime (HMPAO) provides images allowing semiquantitative estimation of regional cerebral blood flow (rCBF). Despite its widespread use there is little data on patterns of rCBF obtained using this tracer in normal elderly subjects, although other methods of measurement suggest a fall in cerebral blood flow with age. Furthermore, the detection of interhemispheric asymmetries on HMPAO SPECT is often used to identify areas of pathological abnormality yet there is little data on the prevalence of asymmetries in the normal elderly. An increased prevalence of asymmetries in the elderly may explain the difficulties recently reported in using functional imaging in the diagnosis of Alzheimer's dementia. Patterns of HMPAO uptake were compared in 10 young (mean age 24.9 years; range 21-34 years) and 10 elderly (mean age 74.1 years; range 70-76 years) normal subjects. Percentage interhemispheric asymmetry ratios were calculated and found to be greater in the elderly, particularly for the temporal cortex (young 0.87%, elderly 3.73%, P < 0.001). The proportion of injected HMPAO taken up by the head was 29% higher in the younger age group. Analysis of regional uptake revealed that this trend towards reduced uptake in the elderly was a global phenomenon affecting all brain regions. The increased interhemispheric asymmetries seen in the elderly imply that a higher threshold for interpreting asymmetries as abnormal must be used in the elderly, particularly for the temporal cortex.

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Abstract: Eighteen cases of lacunar infarction are presented. Six of these cases had a purely motor clinical deficit. All the cases were studied by serial high resolution SPECT (single photon emission computerized tomography) using 99Tcm HMPAO. The degree and extent of the changes in cerebral perfusion consistent with diaschisis were noted and these compared with the severity of the clinical deficit at presentation and over time. No significant correlation between diaschisis and the clinical state was found at any stage. The nature, aetiology and importance of diaschisis are discussed and it is suggested that caution should be exercised in attributing clinical features to diaschisis simply because it may be present.

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Abstract: OBJECTIVE--To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia. PATIENTS--31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied. SETTING--A tertiary cardiac referral centre. DESIGN--Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0.015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1--recordings from areas with a normal perfusion pattern (n = 30), group 2--recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3--recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10). RESULTS--There were changes in the duration of the monophasic action potential indicative of ischaemia--that is, shortening of duration of steady state action potential--in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276.5 (5.3) ms v 276.6 (5.4) for group 1 (NS), 289.6 (4.7) ms v 278.4 (4.9) ms for group 2 (p less than 0.001), and 269.6 (5.7) ms v 242.0 (4.4) for group 3 (p less than 0.0001). These changes were significantly different between the three groups (p less than 0.01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels. CONCLUSIONS--These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.

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Abstract: The GE/CGR Neurocam is a triple-headed single photon emission tomography (SPET) system dedicated to multi-slice brain tomography. We have assessed its physical performance in terms of sensitivity and resolution, and its clinical efficacy in comparison with a modern, single rotating gamma-camera (GE 400XCT). Using a water-filled cylinder containing technetium-99m, the tomographic volume sensitivity of the Neurocam was 30.0 and 50.7 kcps/MBq.ml.cm for the high-resolution (HR) and general-purpose (GP) collimators, respectively; the corresponding values for the single rotating camera were 7.6 and 12.8 kcps/(MBq/ml)/cm. Tomographic resolution was measured in air and in water. In air, the Neurocam resolution at the cente of the field-of-view (FOV) is 9.0 and 10.7 mm full width at half-maximum (FWHM) with the HR and GP collimators, respectively, and is isotropic in the three orthogonal planes; the resolution of the GE 400XCT with 13 cm radius of rotation is 10.3 and 11.7 mm, respectively. For the Neurocam with the HR collimator, the transaxial FWHM values in water were 9.7 mm at the centre and 9.5 mm radial (6.6 mm tangential) at 8 cm from the centre. The physical characteristics of the Neurocam enable the routine acquisition of brain perfusion data with technetium-99m hexamethyl-propylene amine oxime (99mTc-HMPAO) in about 14 min, yielding better image quality than with a single rotating camera in 40 min.

Abstract: In the past 3 years there have been five further cases, in addition to one case reported in 1985, of Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom. The clinical findings of two of these cases are described, demonstrating a typical presentation with a predominantly cerebellar syndrome at onset which is not commonly a presenting feature of sporadic Creutzfeldt-Jakob disease. In one case a 99mTc hexamethylpropylenamine single photon emission tomographic scan showed marked impairment of tracer uptake in the basal ganglia and cerebral cortex at a time when the clinical picture was predominantly cerebellar. This technique may be useful in early diagnosis. In the other case post mortem examination of the brain showed prominent amyloid deposition in the cerebellum, which has not been described previously in pituitary-hormone related Creutzfeldt-Jakob disease. The previously published cases of growth hormone-related Creutzfeldt-Jakob disease are reviewed and reasons for the particular clinical pattern seen are discussed.

Abstract: Recent advances in single photon emission computed tomography (SPECT) have allowed improved image resolution with lower doses of labelled tracer. Capitalizing on these improvements, the authors have developed a new SPECT protocol for imaging neuronal activation. We outline this technique and describe how it can demonstrate increased human motor cortex activity in normal subjects performing a motor task. The ability to accurately demonstrate neuronal activation with SPECT using this method may have important scientific and clinical implications.

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Abstract: In this article guidelines for single-photon emission computerized tomography (SPECT) of the brain are presented by the Task Group "Neurology" of the European Association of Nuclear Medicine (EANM). Under separate headings are discussed: the pathophysiologic principles of various brain diseases, pharmacokinetics and pharmacodynamics of various radiopharmaceuticals, physical principles of SPECT imaging, computerized data processing, clinical protocols and the evaluation of SPECT results.

Abstract: Nuclear medicine has a place in the study of brain trauma, brain tumours, stroke, dementia epilepsy and depression. The development of new tracers labelled with widely available radionuclides, such as technetium-99m (99Tc) and iodine-123, has played a key role here. Practical methodology can now be implemented in the routine setting. Additional applications are reviewed in the context of brain death, encephalitis, post-viral fatigue syndrome, Parkinson's disease and schizophrenia.

Abstract: Structural brain abnormalities have recently been discovered using magnetic resonance imaging in infantile autism, a neurodevelopmental disorder of unknown etiology. However, functional neuroimaging studies in autism using positron emission tomography have had conflicting results and have not explained how the known structural brain abnormalities in autism act in a functioning brain to produce autistic behavior. Using a new technology, high-resolution brain single photon emission tomography, we studied and scanned four young adults with infantile autism and four age-matched controls using the labeled ligand 99mTc-D,L-hexamethyl-propylene amine oxime (99mTc-HMPAO). Total brain perfusion was significantly decreased in autism subjects (range, 58% to 72% of controls, p less than or equal to .02). In addition to the globally decreased perfusion, the autism group also had regionally decreased flow in the right lateral temporal and right, left, and midfrontal lobes compared with controls (p less than or equal to .02, Mann-Whitney t-test).

Abstract: Case reports, numerous brain imaging studies, and certain disease states suggest that the orbital frontal cortex and the striatum are dysfunctional in obsessive-compulsive disorder (OCD). Interest has also grown recently concerning the genetic, neuroanatomic, and clinical links between OCD, chronic motor tics, and Gilles de la Tourette Syndrome (GTS). To test the hypothesis of possible orbito-frontal/basal ganglia dysfunction in GTS, similar to OCD, we studied 20 unmedicated GTS subjects, 10 of whom also had comorbid OCD (GTS/OCD), and 8 control subjects. The subjects were examined with high-resolution single photon emission computed tomography (SPECT) and the labeled regional cerebral blood flow (rCBF) ligand technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO). As a group, GTS subjects showed significantly elevated right frontal/visual cortex activity (mean = 0.879, SD = 0.107) compared with control subjects (mean = 0.798, SD = 0.049). A subanalysis comparing simple GTS versus GTS with comorbid OCD failed to reveal significant differences in regional flow.

Abstract: The definition of viable myocardium after an acute myocardial infarction (MI) is important as it will determine which therapeutic option will be best for the patient. In 201Tl scintigraphy it has been shown that late redistribution (8-24 h) or reinjection may help to identify viable myocardium which does not appear to reperfuse on the 4 h redistribution image. In a prospective study 20 patients with a persistent defect seen on both stress and redistribution images were imaged after reinjection of 201Tl. On visual analysis a total of 180 segments were studied, 85 were normal, 18 reperfused at redistribution and a further nine (in six patients) after reinjection. Bull's-eye analysis at stress demonstrated a mean defect size of 279 pixels, S.D. +/- 74. After redistribution, there was no significant change in mean defect size (227 +/- 96 pixels). At reinjection, there was a significant reduction in mean defect size (189 +/- 107 pixels) (P < 0.05, paired 't'-test). Quantification shows a significant reduction in defect size between stress and reinjection. The use of the 201Tl reinjection technique in patients with a fixed perfusion deficit on stress and redistribution images improves the detection of viable myocardium and is to be preferred to a method of redistribution analysis alone.

Abstract: According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.

Abstract: Conventional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) may show abnormalities in central nervous system Behcet's syndrome but is normal in some cases. Recently in two cases positron emission tomography has shown abnormalities in blood flow and glucose metabolism far more extensive than the abnormalities seen on CT and MRI scans in the same patients. We report a patient with neuro-Behcet's syndrome presenting with headache and personality change in whom CT and MRI brain imaging was normal, but regional cerebral blood flow imaging using single photon emission tomography with the tracer HMPAO showed extensive perfusion deficits which partially reversed after 3 months of prednisolone therapy. This technique may aid the diagnosis of cerebral involvement in Behcet's syndrome, although the cause and incidence of the perfusion deficits need further evaluation.

Abstract: Vigabatrin is a specific gamma-aminobutyric acid transaminase inhibitor. The clinical use of this drug in the treatment of epilepsy has been sporadically linked to the development of psychosis. Using 123I-IBZM, a specific dopamine D2 receptor ligand and single photon emission tomography (SPET), one month of treatment with vigabatrin was associated with a decrease in specific binding of 123I-IBZM to D2 receptors in the left hemisphere basal ganglia. This change may provide one explanation for the development of psychosis in vulnerable patients.

Abstract: We report on the utility of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) to diagnose brain death following cardiac surgery on a 49-year-old man with triple-vessel coronary artery disease. The imaging parameters and criteria to diagnose irreversible brain damage (brain death) with 99mTc-HMPAO are outlined. Brain imaging with this tracer seems to be more reliable than classic radionuclide angiography and has a potential value to confirm the diagnosis of brain death at an early stage. In addition, it may be used to evaluate the perfusion pattern to other vital organs with potential for transplantation.

Abstract: Traumatic intracerebral haematomas are a common neurosurgical emergency. Their management, particularly the role of surgical removal, is controversial. Deterioration often occurs late, and is unpredictable. Eight patients with traumatic intracerebral haematomas were admitted to the neurosurgical unit to monitor their clinical state. All were studied within 48 hours of admission with single photon emission computerised tomography (SPECT), using the recently introduced radionuclide 99Technetiumm-Hexamethyl propylene amine oxime (99Tcm-HMPAO). At the time of the SPECT study, all the patients had been clinically stable. Three patients remained so; in the other five, the conscious level deteriorated, necessitating craniotomy and evacuation of the haematoma. In all the patients, the SPECT studies demonstrated perfusion defects that corresponded to the location of the haematoma, as demonstrated by computerised tomography (CT). However, in the five patients who subsequently deteriorated, the perfusion defects seen on the SPECT scan appeared larger than the haematoma, as seen on the CT scan. In addition, there was widespread poor retention of 99Tcm-HMPAO in the ipsilateral hemisphere. These differences were quantifiable. Interestingly, these differences were present at a time when the patients were clinically stable, before their deterioration. It is concluded that SPECT studies with 99Tcm-HMPAO are of possible use as predictors of late deterioration in the management of traumatic intracerebral haematomas.

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Abstract: In a study designed to appraise the use of monophasic action potentials (MAPs) to detect myocardial ischemia in endocardial recordings, changes in steady-state MAP duration were compared in recordings between normal and ischemic areas of myocardium identified by the use of a radionuclide tracer simultaneously with the MAP recording procedure. Single-site recordings were made from the left or right ventricular endocardium or both in 26 patients (32 recording sites) during atrial pacing up to angina threshold. Pacing was maintained for 2 minutes at each increment in heart rate and MAPs were recorded at the end of each 2-minute period. Perfusion defects produced by atrial pacing stress were detected using technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile injected at peak pacing stress. In 18 recordings from normally perfused areas of endocardium, MAP duration at 70% and 90% repolarization shortened by a mean (+/- SD) of 20.9 (3.7) msec and 22.0 (4.8 msec, respectively, for every 100 msec change in cycle length. This is in keeping with the effect of cycle length changes on the action potential duration. The extent of shortening was significantly greater (p less than 0.01) for 14 recordings from ischemic areas, being 32.0 (8.6) and 33.8 (9.7) msec, respectively, indicating the additional effect of localized myocardial ischemia. These results validate the applicability of the endocardially recorded MAPs for the detection of ischemia. Such methodology may provide a means of assessing therapeutic interventions aimed at the early phase of ischemia.

Abstract: Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cerebral activating procedures within the scan protocol enables investigation of the mechanisms involved in specific brain functions in health and disease. Activation studies involve the comparison of at least two data sets describing brain activity generated in conditions that differ for the specific function in question. When designing an activation study, decisions regarding methodology include: the nature of the activation regime, the tracer-ligand utilized, the SPET instrument and the manner of subsequent data analysis. These issues are discussed in this review, both theoretically and with reference to published studies. Means of activating particular cerebral structures and functions are reviewed, as are the limitations of the techniques with respect to temporal and spatial resolution and the potentially confounding nature of preconceived ideas regarding the mechanisms of brain function.

Abstract: 3-Iodo-6-methoxybenzamide (123I-IBZM), a new Dopamine D2 receptor ligand, was used in conjunction with SME 810 brain tomography to study six subjects (one normal volunteer, four schizophrenics and one DAT patient). Initial Dynamic SPET was followed by multislice SPET. High-resolution images of the D2 receptor distribution in the basal ganglia were obtained. The specific binding in D2 receptors of the basal ganglia is highest from 2-4 h p.i. Patients on anti-psychotic drugs showed significantly lower specific binding. Dopamine D2 brain receptor availability in man may now be studied with SPET. Continuous data acquisition with single slice tomography is particularly important in the study of this type of radiotracers.

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Abstract: Twenty patients satisfying standard clinical criteria for Alzheimer's disease (AD) and six age-matched normal controls were studied using 99mTc hexamethyl-propyleneamine oxime and single photon emission tomography. The AD patients had lower regional cerebral blood flow (rCBF) in the temporal and posterior parietal lobes compared to controls. AD patients with apraxia and aphasia had lower rCBF in the lateral temporal and posterior parietal lobes than AD patients without these features. Within the AD group, correlations were found between neuropsychological tests and rCBF: praxis correlated with posterior parietal activity, memory with left temporal lobe activity and language with activity throughout the left hemisphere.

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Abstract: Single photon emission tomography (SPET) studies using 99Tcm-HMPAO are in widespread use in the functional imaging of cerebral blood flow (CBF). While qualitatively the images correlate well with other imaging modalities, there are doubts as to the quantitative accuracy of this method. In particular, the uptake and subsequent retention of 99Tcm-HMPAO in conditions of high flow is known to be nonlinear. In this study, we compared the quantitative retention of 99Tcm-HMPAO in eight subjects under conditions of normo- and hypercapnia. There was no significant increase, despite a mean rise of the end tidal pCO2 from 5.06 to 7.06 kPa, a stimulus that is known to provoke an 80-100% rise in CBF. We conclude that SPET studies with 99Tcm-HMPAO provide excellent qualitative images of the distribution of CBF, but that quantitative data in ml hg-1 min-1 must be interpreted with caution.

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Abstract: The intracellular localization and relative distribution of 99Tcm-hexamethylpropyleneamine-oxime (99Tcm-d, l-HMPAO) and 201Tl-diethyldithiocarbamate (201Tl-DDC), which have been used to assess regional cerebral blood flow (rCBF) in man, were investigated in rat brain. 99Tcm-d, l-HMPAO was found attached mainly to cell organelles whilst 201Tl-DDC was localized mainly in free state in the cytosolic fraction. Isolation of neuronal and glial nuclei showed that there is higher uptake of 99Tcm-d, l-HMPAO in neuronal nuclei than in glial nuclei for all the different regions of the rat brain investigated. These data demonstrate a different subcellular localization of the two lipophilic agents studied. In view of their proposed clinical utility, this difference merits further investigation.

Abstract: In this study a comparison between the classical (111In oxine) and the newer (99Tcm HMPAO) technique of labelling leucocytes is reported. The behaviour in vivo and the relative sensitivity in the detection of infection (chest and bone) and inflammatory bowel disease (IBD) is presented. Simultaneous dual-radionuclide gamma camera acquisition methodology was applied to study 99 patients, 18 with chest infection, 26 with bone infection, 41 with IBD and 14 with other pathological conditions. The mean (1 SD) 50% washout time from the lungs was 483.03 (79.10) s for 99Tcm HMPAO-labelled white blood cells and 475.85 (83.79) s for 111In oxine-labelled white cells (r = 0.81). Concordance between the two techniques was 94% in the chest-infection group of patients, 88% in the bone-infection group and 71% in the localization of IBD.

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Abstract: We present preliminary data on the utility of functional brain imaging with [99mTc]-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the "on-off" syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibited patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the "on-off" syndrome studied during an "on" phase (under levodopa therapy) and on another occasion after withdrawal of levodopa ("off") demonstrated a significant change in the uptake of [99mTc]-d,l-HM-PAO in the caudate nucleus (lower on "off") and thalamus (higher on "off"). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. [99mTc]-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.

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Abstract: The radionuclide tracer method is unique amongst all other imaging methodologies in its ability to trace organ or tissue function and metabolism. It derives this advantage from the nature of the signal used for image generation, and its single interaction with the organ or system under examination. Physical processes such as electron or proton density assessment or resonance, edge identification, electrical or ultrasonic impedence, do not pertain to the image generation process in nuclear medicine, and if so, only in a rather secondary manner. The nuclear medicine imaging study is primarily a study of the chemical nature, distribution and interaction of the tracer/radiopharmaceutical utilised with the cellular system which requires investigation: the thyroid cells with sodium iodide, the recticular endothelial cells with colloidal particles, the adrenal medulla cells with metaiodobenzylguanidine, and so on. In the two most recent areas of nuclear medicine expansion, oncology (with labelled monoclonal antibodies) and neurology and psychiatry (with a whole new series of lipid soluble radiopharmaceuticals), specific cell systems can also be targeted and hence imaged and investigated. The study of structure as masterly performed by Virchow and all his successors over more than a century, is now definitely the prerogative of such imaging systems which excel with spatial and contrast resolution (x-ray computed transmission tomography, nuclear magnetic resonance imaging, diagnostic ultrasound). However the investigation of function and metabolism (as performed by Claude Bernard, Georg von Hevesy, and so many others), has clearly passed from the laboratory animal protocol and experiment to the direct investigation in man, this being the achievement of the radionuclide tracer methodology. In this article, we review present interest and developments in that part of nuclear medicine activity which is aimed at the study of the neurological or psychiatric patient.

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Abstract: The distribution of 99Tcm-HM-PAO is described in normal man. Since our initial report on the clinical potential of this new radiopharmaceutical in 1984, a number of clinical trials are in progress worldwide. As the tracer has been designed to enable the in vivo assessment of the distribution of cerebral blood flow in man, significant interest in this new 99Tcm-labelled compound can be detected not only in the nuclear medicine practice in general, but in the more specialist areas of medicine such as neurology and psychiatry. In this paper we report findings which should aid in the evaluation of this compound in normal individuals.

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