Abstract: OBJECTIVES: To assess the cost-effectiveness of three colorectal-cancer (CRC) screening strategies in France: fecal-occult-blood tests (FOBT), computed-tomography-colonography (CTC) and optical-colonoscopy (OC). METHODS: Ten-year simulation modeling was used to assess a virtual asymptomatic, average-risk population 50-74 years old. Negative OC was repeated 10 years later, and OC positive for advanced or non-advanced adenoma 3 or 5 years later, respectively. FOBT was repeated biennially. Negative CTC was repeated 5 years later. Positive CTC and FOBT led to triennial OC. Total cost and CRC rate after 10 years for each screening strategy and 0-100% adherence rates with 10% increments were computed. Transition probabilities were programmed using distribution ranges to account for uncertainty parameters. Direct medical costs were estimated using the French national health insurance prices. Probabilistic sensitivity analyses used 5000 Monte Carlo simulations generating model outcomes and standard deviations. RESULTS: For a given adherence rate, CTC screening was always the most effective but not the most cost-effective. FOBT was the least effective but most cost-effective strategy. OC was of intermediate efficacy and the least cost-effective strategy. Without screening, treatment of 123 CRC per 10,000 individuals would cost €3,444,000. For 60% adherence, the respective costs of preventing and treating, respectively 49 and 74 FOBT-detected, 73 and 50 CTC-detected and 63 and 60 OC-detected CRC would be €2,810,000, €6,450,000 and €9,340,000. CONCLUSION: Simulation modeling helped to identify what would be the most effective (CTC) and cost-effective screening (FOBT) strategy in the setting of mass CRC screening in France.
Abstract: Contrast-enhanced ultrasound (CEUS), with the recent development of both contrast-specific imaging modalities and microbubble-based contrast agents, allows noninvasive quantification of microcirculation in vivo. Nevertheless, functional parameters obtained by modeling contrast uptake kinetics could be impaired by respiratory motion. Accordingly, we developed an automatic respiratory gating method and tested it on 35 CEUS hepatic datasets with focal lesions. Each dataset included fundamental mode and cadence contrast pulse sequencing (CPS) mode sequences acquired simultaneously. The developed method consisted in (1) the estimation of the respiratory kinetics as a linear combination of the first components provided by a principal components analysis constrained by a prior knowledge on the respiratory rate in the frequency domain, (2) the automated generation of two respiratory-gated subsequences from the CPS mode sequence by detecting end-of-inspiration and end-of-expiration phases from the respiratory kinetics. The fundamental mode enabled a more reliable estimation of the respiratory kinetics than the CPS mode. The k-means algorithm was applied on both the original CPS mode sequences and the respiratory-gated subsequences resulting in clustering maps and associated mean kinetics. Our respiratory gating process allowed better superimposition of manually drawn lesion contours on k-means clustering maps as well as substantial improvement of the quality of contrast uptake kinetics. While the quality of maps and kinetics was satisfactory in only 11/35 datasets before gating, it was satisfactory in 34/35 datasets after gating. Moreover, noise amplitude estimated within the delineated lesions was reduced from 62 ± 21 to 40 ± 10 (p < 0.01) after gating. These findings were supported by the low residual horizontal (0.44 ± 0.29 mm) and vertical (0.15 ± 0.16 mm) shifts found during manual motion correction of each respiratory-gated subsequence. The developed technique could be used as a basis for accurate quantification of perfusion parameters for the evaluation and follow-up of patients under antiangiogenic therapies.
Abstract: PURPOSE: To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. MATERIALS AND METHODS: All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, high-acoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves reflects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests. RESULTS: The lowest excised mean tumor weights (+/- standard deviation) corresponded to the longest bevacizumab-treatment duration: 1.4 g +/- 1.1 (continuous-treatment) compared with 2.3 g +/- 2.1 (discontinued) and 3.7 g +/- 1.9 (control) (P = .01). On day 35, the respective control and continuously treated groups had comparable and significantly larger necrotic areas: 37% +/- 14 and 32% +/- 17 larger than the discontinued-treatment group (15% +/- 9; P < .05). Normalized perfusion increased significantly with time (P = .02) in the discontinued-treatment group after therapy ceased (day 22). CONCLUSION: Noninvasively measured contrast-enhanced US parameters demonstrated tumor revascularization after stopping antiangiogenic therapy in this murine tumor model.
Abstract: Angiogenesis regulation is one of the newest fronts in the fight against cancer. Anti-angiogenic therapy is based on inhibiting factors required to solicit vessel formation thus cutting-off the tumor's supply of nutriments and oxygen. Initial vascular response is followed by formation of necrosis. Volumetric regression occurs more tardively. Effective monitoring of this new therapeutic approach thus requires imaging techniques that can detect early microvascular changes. A number of clinical studies provide evidence that contrast-enhanced ultrasound (CEUS) can provide early indication of tumor response to anti-angiogenic therapy. More sophisticated imaging and analysis techniques for CEUS and contrast agents targeted for adhesion to anti-angiogenic markers have also demonstrated promise in animal model studies. This review underlines the relevance of CEUS for anti-angiogenic therapy monitoring by summarizing the current clinical results, emerging CEUS techniques and preclinical data.
Abstract: OBJECTIVES: To prospectively assess an innovative computer-aided diagnostic technology that quantifies characteristic features of backscattered ultrasound and theoretically allows transvaginal sonography (TVS) to discriminate benign from malignant adnexal masses. METHODS: Women (n = 264) scheduled for surgical removal of at least one ovary in five centres were included. Preoperative three-dimensional (3D)-TVS was performed and the voxel data were analysed by the new technology. The findings at 3D-TVS, serum CA125 levels and the TVS-based diagnosis were compared with histology. Cancer was deemed present when invasive or borderline cancerous processes were observed histologically. RESULTS: Among 375 removed ovaries, 141 cancers (83 adenocarcinomas, 24 borderline, 16 cases of carcinomatosis, nine of metastases and nine others) and 234 non-cancerous ovaries (107 normal, 127 benign tumours) were histologically diagnosed. The new computer-aided technology correctly identified 138/141 malignant lesions and 206/234 non-malignant tissues (98% sensitivity, 88% specificity). There were no false-negative results among the 47 FIGO stage I/II ovarian lesions. Standard TVS and CA125 had sensitivities/specificities of 94%/66% and 89%/75%, respectively. Combining standard TVS and the new technology in parallel significantly improved TVS specificity from 66% to 92% (p < 0.0001). CONCLUSIONS: Computer-aided quantification of backscattered ultrasound is a highly sensitive for the diagnosis of malignant ovarian masses.
Abstract: PURPOSE: To compare enhancement of liver parenchyma in MR imaging after injection of hepatocyte-specific contrast media. MATERIALS AND METHODS: Patients (n = 295) with known/suspected focal liver lesions randomly received 0.025 mmol gadoxetic acid/kg body weight or 0.05 mmol gadobenate dimeglumine/kg body weight by means of bolus injection. MR imaging was performed before and immediately after injection, and in the delayed phase at approved time points (20 min after injection of gadoxetic acid and 40 min after injection of gadobenate dimeglumine). The relative liver enhancement for the overall population and a cirrhotic subgroup was compared in T1-weighted GRE sequences. An independent radiologist performed signal intensity measurements. Enhancement ratios were compared using confidence intervals (CIs). RESULTS: The relative liver enhancement in the overall population was superior with gadoxetic acid (57.24%) versus gadobenate dimeglumine (32.77%) in the delayed-imaging phase. The enhancement ratio between the contrast media was statistically significant at 1.75 (95% CI: 1.46-2.13). In the delayed phase, the enhancement of cirrhotic liver with gadoxetic acid (57.00%) was comparable to that in the overall population. Enhancement with gadobenate dimeglumine was inferior in cirrhotic liver parenchyma (26.85%). CONCLUSION: In the delayed, hepatocyte-specific phase, liver enhancement after injection of gadoxetic acid was superior to that obtained with gadobenate dimeglumine.
Abstract: The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.
Abstract: PURPOSE: To determine the performance of a CAD system for lung nodules with ground glass opacity component on multidetector-row CT. Materials and methods. The CT examinations of 17 patients with at least one persistent subsolid nodule were reviewed. A first non-blinded consensus review by two expert radiologists resulted in the detection of 104 subsolid nodules larger than 3 mm (74 nodules of ground glass attenuation and 30 mixed nodules with solid and ground glass components). The results from this review were used as a gold standard to determine the performances of the CAD system and 3 independent clinical radiologists involved with the primary interpretations. RESULTS: The sensitivity of the CAD system for the detection of ground glass opacities and mixed nodules was 53% and 73% respectively. These values were not statistically different from the values for the 3 independent observers (42-66% for ground glass opacities and 63-80% for mixed nodules). The sensitivity of each observer significantly increased when the nodules detected by the CAD system were added to those detected by each observer (p<0.0001). CONCLUSION: A CAD system has a potential impact on the detection rate of subsolid nodules by radiologists.
Abstract: The appearance of the normal postsurgical liver and of potential complications specific to the type of liver resection performed (partial hepatectomy, cyst fenestration, RF ablation) must be well known by radiologists for early detection and treatment of postoperative complications. Early postoperative imaging of the liver aims at detecting vascular, biliary and extrahepatic complications and relies mainly on Doppler US and CT.
Abstract: Quantitative analysis of tissue perfusion using contrast-enhanced ultrasound is still limited by shadowing, which is caused by inadequate compensation for microbubble contrast agent attenuation. Many previous methods have been developed for attenuation correction in soft tissues. However, no method has been proposed to correct for microbubble attenuation in vivo. In this article, a model to estimate microbubble attenuation is presented, using the time-intensity variation in a highly echogenic distal area without contrast uptake. This model is based on the assumption that a linear relationship holds between local microbubble attenuation and local backscatter. The model was applied to 12 murine renal perfusion studies. Parametric images of microbubble attenuation were generated, corresponding to dynamic contrast agent-specific sequences without shadowing. Contrast uptake kinetics consistent with the physiology were retrieved in all perfused areas. This method therefore proved to be of potential interest in the quantification of tissue perfusion in small animal studies.
Abstract: Polymeric capsules with a thick shell made of biodegradable and biocompatible polymer and a liquid core of perfluorooctyl bromide (PFOB) were evaluated for stability as well as for ultrasound and magnetic resonance imaging (MRI) contrast enhancement. The method of preparation allows the mean capsule diameter to be regulated between 70 nm and 25 µm and the capsule thickness-to-radius ratio from 0.25 to 0.54. Capsule diameter remains stable at 37 °C in phosphate buffer for at least 4 and 6 h for nanocapsules and microcapsules, respectively. The in vitro ultrasound signal-to-noise ratio (SNR) was measured from 40 to 60 MHz for 6 µm and 150 nm capsules: the SNR increases with capsule concentration up to 20–25 mg mL−1, and then reaches a plateau that depends on capsule diameter (13.5 ± 1.5 dB for 6 µm and 6 ± 2 dB for the 150 nm capsules). The ultrasound SNR is stable for up to 20 min for microcapsules and for several hours for nanocapsules. For nanocapsules, the thinner the shell, the larger the SNR and the more compressible the capsules. Nanocapsule suspensions imaged in vitro with a commercial ultrasound imaging system (normal and tissue harmonic imaging modes, 7–14 MHz probe) were detected down to concentrations of 12.5 mg mL−1. Injections of nanocapsules (200 µg ml−1) in mice in vivo reveal that the initial bolus passage presents significant ultrasound enhancement of the blood pool during hepatic imaging (7–14 MHz probe, tissue harmonic imaging mode). 19F-MRI images were obtained in vitro at 9.4T using spin-echo and gradient echo sequences and allow detecting nanocapsules in suspension (50 mg mL−1). In conclusion, these results show initial feasibility for development of these capsules toward a dual-modality contrast agent
Abstract: The aim of this paper was to validate the combination of two original methods for assessing perfusion in small animal studies using Contrast-Enhanced Ultrasound. Respiratory motion was first removed using a frame selection method. This method, based on a Principal Component Analysis, enabled the definition of two subsequences, corresponding to the end-of-inspiration plane and to the end-of-expiration plane. Attenuation caused by contrast agent microbubbles was then estimated. The developed method, based on the assumption that a linear relationship holds between local attenuation and backscatter, used the time-intensity variation in a highly echogenic distal area without contrast uptake to estimate local attenuation coefficients. Ten murine renal perfusion studies were investigated after a bolus injection of SonoVue. Replenishment kinetics were acquired too and were finally modeled with an exponential function. Preliminary results were promising. Indeed, the SonoVue concentration was more faithfully represented than on native images, which allowed a better assessment of perfusion parameters in the whole field of view.
Abstract: Despite recent advances in contrast-enhanced ultrasound imaging, evaluation of tissue perfusion with contrast-enhanced ultrasound is still impaired by shadowing effects. These effects are particularly relevant in small animal studies due to high frequency imaging. Current methods of tissue attenuation correction are not suited for contrast-enhanced ultrasound examinations, because microbubble acoustic response to ultrasound waves is far more complex than that of tissues. A method allowing in vivo tissue attenuation correction in the presence of contrast agents is presented.
Abstract: OBJECTIVES: Evaluate the improvement in detecting lung nodules when using multidetector CT (MDCT) computer-assisted diagnosis (CAD). MATERIAL AND METHODS: Three radiologists (R1, R2, R3) with different levels of experience independently interpreted 30 MDCT examinations of the thorax taken for screening purposes, first without and then with CAD. The diagnosis was established by two of the three radiologists interpreting the images together, assisted by the CAD. RESULTS: The consensus reading identified 133 nodules, 61 (46%) of which were 4 mm or larger. The sensitivity values in the detection of nodules before and after using the CAD were 54% and 80% (R1), 38% and 71% (R2), and 70% and 88% (R3), respectively. When considering only the nodules that were 4 mm or larger, the sensitivity values varied before and after using the CAD, from 62% to 95% (R1), from 41% to 84% (R2), and from 74% to 92% (R3). By combining two by two the three radiologists' results obtained without the CAD, the sensitivity values were 65%, 83%, and 77%, respectively, for all the nodules, and 70%, 85%, and 77% for the nodules that were 4 mm or larger. The CAD induced a total of 105 false-positive results, with a mean of 3.5 per examination. CONCLUSION: The lung nodules missed by the radiologist can be detected if the CAD is used as a second reader. The CAD can be at least as beneficial as the use of a second independent reader.
Abstract: PURPOSE: To determine whether contrast-enhanced ultrasound (CEUS) can aid in assessing treatment efficacy within the first 2 weeks after transarterial chemoembolization for hepatocellular carcinoma. MATERIALS AND METHODS: Contrast-enhanced ultrasound was performed to detect residual tumor blood flow after 42 transarterial chemoembolization procedures in 33 patients who had hepatocellular carcinomas, and the results were compared with final tumor outcome. Twenty-nine CEUS studies were performed within 2 weeks after treatment and the remainder within 1 month. Phase-inversion low-mechanical-index real-time and intermittent imaging were performed after the intravenous injection of 0.5-2 mL US contrast medium by experienced radiologists blind to all other imaging findings. RESULTS: Nine tumors did not reach final outcome--patients were lost to follow-up or died without autopsy (n = 6) or tumors were retreated before final outcome was established (n = 3). Of the remaining 33 tumors, outcome was established by histology (n = 9), angiography (n = 14), tumor growth (n = 2), or by computed tomography and/or magnetic resonance imaging performed more than 6 months after treatment (n = 8). Twenty-three tumors were studied by CEUS within 2 weeks and 10 within 1 month after treatment. Of these 33 tumors, there were no false-negative results and one false-positive result. The only error occurred when the CEUS study was performed within 1 day after treatment. CONCLUSIONS: Residual tumor blood flow on CEUS performed at 2 or more days after transarterial chemoembolization may be predictive of tumor outcome that currently requires 3 months to be reliably detected by computed tomography and/or magnetic resonance imaging.
Abstract: PURPOSE: To evaluate quantitative functional ultrasonography (US) in a murine gel model by using microbubble destruction kinetics to determine whether parametric indices provided with US could help assess angiogenesis. MATERIALS AND METHODS: Institutional Animal Subjects Committee approved experiments and procedures. In 36 normal mice, two 0.4-mL gel implants were placed subcutaneously on either side of spine. One implant contained 0.5, 1.0, or 1.5 microg human basic fibroblast growth factor (bFGF) per milliliter of gel. Functional US quantitative analysis of angiogenesis with microbubble contrast agent was performed on days 3, 6, 9, and 12; histologic data were collected. Time-intensity curve of implant was fitted to mathematic decay model to calculate fractional blood volume and fraction of blood replaced per unit of time. Microvascular density (MVD) and percentage of microvascular area (MVA) were measured after anti-CD31 staining. Spearman rank order correlation was used in analyses. RESULTS: bFGF-containing implants induced MVD of eight, 35, 42, and 42 vessels per square millimeter on days 3, 6, 9, and 12, respectively; in controls, MVD was four vessels/mm2 (P<.05 on days 6, 9, and 12). bFGF-containing implants induced percentage MVA of 2%, 5%, 20%, and 27%, respectively; in controls, it was 0.5% (P<.05). Maximum enhancement was significantly increased in bFGF implants (23.3 gray level+/-14.1 [standard deviation]) compared with controls (11.0+/-5.5, P<.001). Implants containing bFGF showed poor correlations between fractional blood volume and MVD (r2=0.42) or percentage MVA (r2=0.51) at US. There was no correlation between microbubble velocity and MVD (r2<0.05) or percentage MVA (r2<0.13). CONCLUSION: Functional US perfusion parameters do not correlate with current histologic indices for quantifying angiogenesis. MVD, as a histologic quantitative measurement of angiogenesis, may not be an appropriate standard for contrast-enhanced imaging that relies on perfused neovessels.
Abstract: This article updates the description of an anatomical variation of the liver, in which the gallbladder is adjacent to the ligamentum teres, that was described until now as "right-sided ligamentum teres and right umbilical portion of the portal vein". A study of eight patients showing this anatomical variation has led to a new archetypal anatomical description of the hepatic and portal veins, using multidetector-row computed tomography (MDCT) with three-dimensional (3D) volume-rendering (VR) reconstructions. While 2D axial imaging gave the same information, MDCT imaging with VR reconstructions provided a clear 3D visualization of this anatomical variation. Typical features can be described as follows: (1) juxtaposition of the ligamentum teres and the gallbladder; (2) typical portal vein branching with a right posterior branch, a left posterior branch and a main medial branch that terminates in the ligamentum teres; (3) two main hepatic veins and a hypotrophied medial hepatic vein. We think, based on the direct comparison of anatomical findings and knowledge of chronological embryological development, that this abnormality results from the defective development of the central part of the liver and not from the persistence of the right rather than the left umbilical vein. Because of the presence of only one medial plane, containing both the gallbladder and the ligamentum teres, we propose renaming it "fusion of hepatic planes".
Abstract: BACKGROUND: Alignment of the gallbladder fossa and the round ligament may be associated with an almost unknown portal vein branching anomaly. STUDY DESIGN: Ultrasonographic imaging allowed detection of this anomaly, which we characterized as fusion of the planes of the liver. When appropriate, additional specific radiologic examinations were performed (CT scanner supplemented with a three-dimensional reconstruction, a biliary cartography, or an angiography). Surgical consequences were studied from this series and from the literature. RESULTS: Seven patients (0.5%) had the following criteria: 1) round ligament, gallbladder fossa, and termination of the portal vein occurring in the same plane; 2) typical portal vein branching, including a right posterior branch, left branches, and a main medial branch terminated by the Rex's recessus; 3) two main hepatic veins without a significant middle hepatic vein; and 4) absence of the horizontal part of the left hepatic duct. Fusion of the planes may have been involved in two cases of iatrogenic bile duct injury and contraindicated a tumor resection and a right-liver donation. A review of the literature revealed that lack of recognition of the fusion of the planes led to a high proportion of surgical iatrogenic injury. Fusion of the planes could result from incomplete development of the central part of the liver, in agreement with embryologic knowledge. CONCLUSIONS: Knowledge of the fusion of the planes by hepato-biliary surgeons is important. This anomaly may lead to serious complications if it remains undetected during liver resection or bile duct surgery.
Abstract: Preventing complications during hepatic surgery in living-donor transplantation or in oncologic resections requires a careful preoperative analysis of the hepatic venous anatomy. Such an analysis relies on CT hepatic venography data, which enhances the vascular structure due to contrast medium injection. However, a 3D investigation of the enhanced vascular anatomy based on typical computer vision tools is ineffective because of the large amount of occlusive opacities to be removed. This paper proposes an automated 3D approach for the segmentation of the vascular structure in CT hepatic venography, providing the appropriate tools for such an investigation. The developed methodology relies on advanced topological and morphological operators applied in mono- and multiresolution filtering schemes. It allows to discriminate the opacified vessels from the bone structures and liver parenchyma regardless of noise presence or inter-patient variability in contrast medium dispersion. The proposed approach was demonstrated at different phases of hepatic perfusion and is currently under extensive validation in clinical routine.
Abstract: OBJECTIVE: Our goal was to develop a reliable technique that has minimal operator dependence for quantifying lymph node enhancement to test and optimize new sonography contrast formulations. MATERIALS AND METHODS: Twenty healthy rabbits were studied using five agents, labeled A-G. Agents D and E were the same agent and agents F and G were Imagent, studied blindly to test reproducibility. One milliliter of contrast agent was injected into each hind footpad. A 13-MHz transducer was fixed over the popliteal node, which was imaged at a 4.8-MHz central transmit frequency using phase-inversion technology at 100% power and one frame per second. Immediately after each injection, the footpad was massaged 12 times for 30 sec each time and then imaged after each massage to assess the number of times the node could be refilled from each injection. Lymph node video intensity was measured, and the degree of enhancement was evaluated using analysis of variance with the massage number and the agent used as independent variables. RESULTS: Lymph node enhancement was observed after the first massage with all agents. Degree of enhancement was least with agents A and B, intermediate with agents D and F, and greatest with agent C. Agent A was effective after the first two massages, agent B after the first four, agent C after all 12, agent D after the first eight, and agent F after the first nine. Performance of agents D and F was similar to that of their duplicates, E and G. CONCLUSION: We established a reproducible technique to quantify lymph node enhancement that can distinguish between different agents. The differences in performance suggest that it is possible to optimize agent formulation for indirect sonographic lymphography.
Abstract: RATIONALE AND OBJECTIVES: To optimize an angiogenesis model for imaging research that is stable and can be imaged several times over the angiogenic time course. MATERIALS AND METHODS: Mice and rats received two injections of 0.4 mL of extract of basement membrane matrix (Matrigel; Becton Dickinson Labware, Bedford, MA) in the subcutaneous spaces on either side of the spine. One of the two Matrigel plugs in each animal had either 0.1 microg/mL of basic fibroblast growth factor (bFGF) (11 mice), 1.0 microg/mL of bFGF (12 mice, 5 rats), or 1.0 microg/mL of bFGF and 60 U/mL of heparin (11 mice). Three to 12 days after implantation, animals were imaged before and after the administration of up to four injections of 0.1 mL AF0150. Phase inversion imaging was used on a Siemens Elegra (Siemens ultrasound, Issaquah, WA) equipped with a 13 MHz VFX transducer. Three observers subjectively assessed the pattern of enhancement using a four-point scale. The Matrigel plugs were then removed and two observers graded the angiogenic response on a four-point scale. Ten Matrigel plugs, five with 1.0 microg/mL bFGF and five without, were evaluated histologically following immunohistochemical staining with anti-CD31. RESULTS: The angiogenic response was greater in Matrigel plugs with 1.0 than with 0.1 microg/mL of bFGF. Heparin did not increase the angiogenic response. Vessels were predominantly at the periphery of the plugs with variable central penetration. Plugs appeared anechoic and homogeneous on ultrasound. Contrast enhancement within the plug occurred in 44% of mice with an angiogenic response at or after day 6 and the enhancement increased with the angiogenic response. In the others, peripheral enhancement could not be distinguished from the enhancement of surrounding tissues that were also hyperemic. The thicker rat skin interfered with plug assessment. CONCLUSION: A stable angiogenesis model without the complexity of tumors is described. This model offers the opportunity to image the development and/or inhibition of angiogenesis. Neovasculature in Matrigel was detectable using ultrasound contrast. Quantitative studies correlating the degree of enhancement to microvascular density will be determined in subsequent studies.
Abstract: The aim of this study was to correlate sonographic abnormalities of the rotator cuff with clinical findings in veteran tennis players. One hundred fifty individuals playing competition-level tennis, aged from 35 to 77 years (mean age 55 years), underwent physical and US examinations of their shoulders. The US abnormalities found in the dominant shoulder were compared with those observed in the non-dominant shoulder and in different subsets of players defined by the absence or presence of former and/or current pain. Tears of the long head of the biceps tendon were seen only in dominant shoulders ( n=8), and tears (23 complete and 20 partial) of the supraspinatus tendon were observed in 43 dominant vs 16 (3 complete and 13 partial) contralateral shoulders ( p<0.001). Subscapularis tendon calcifications were depicted in 23 dominant vs 12 contralateral shoulders ( p<0.05). Seventy players had no pain, 49 had former-but-not-current pain, and 31 had current pain. Abnormal thickening (>2 mm) and effusion of the subacromial-subdeltoid bursa and complete tear of the supraspinatus tendon were more frequent in the latter two groups ( p<0.001 and p<0.05), respectively. Although 90% of the players with a complete supraspinatus tear had experienced former pain, no relationship was found between current pain and the presence of a supraspinatus tear or tendon calcification. The rotator cuff may present important asymptomatic lesions, such as complete tears of the supraspinatus tendon or calcifications, that do not prevent the playing competitive tennis. The only US abnormality associated with pain was subacromial-subdeltoid bursa effusion.
Abstract: The purpose of our study was to evaluate the ability of superparamagnetic iron oxide (SPIO)-enhanced MR imaging to detect liver fibrosis in patients with chronic liver disease and to compare the findings with histopathological data. Sixty-seven patients with chronic hepatitis ( n=58) or focal nodular hyperplasia (FNH; n=9) were studied using a 1.5-T MR system. The protocol included proton density-weighted, T2-weighted spin-echo (SE) and fast SE (FSE) sequences before and after SPIO administration and T2*-weighted gradient-recalled-echo (GRE) sequences after SPIO. Pre- and post-contrast T2-weighted and T2*-weighted sequences were retrospectively evaluated by three independent observers for evidence of non-tumor hypersignal intensities. Three liver patterns were considered: thick reticulations; thin reticulations; and/or multiple areas of hypersignal intensities. Unenhanced or enhanced patterns were compared with histopathological specimens, which had been obtained by percutaneous biopsy of the right lobe within a maximum of 12 months of MR examination. Liver fibrosis was histologically graded using a five-level scale (F0-F4), according to the METAVIR classification. Histopathology demonstrated significant fibrosis (F2-F4) in 57 patients, non-significant fibrosis in 1 patient (F1), and normal liver surrounding FNH in 9 patients (F0). After SPIO administration, at least one pattern of non-tumor hypersignal intensities was seen in 43 (76%) of the 57 patients with F>/=2 with good agreement (kappa=0.68) compared with 2 (20%) of the 10 F0/1 patients ( p<0.01). Attenuated non-homogeneous liver-signal intensities with persistent thick reticulations, thin reticulations, or multiple areas of hypersignals were observed in, respectively, 30, 52, and 56% of patients with F>/=2 with moderate agreement (kappa=0.51). Before SPIO, MR images were positive in 21 of 57 (37%) F>/=2 and zero F0/1 patients. Post-contrast proton-density-weighted and T2*-weighted GRE were the most sensitive sequences for detecting non-tumor hypersignal intensities. In patients with chronic liver diseases, SPIO-enhanced MR imaging exhibits non-tumor hypersignal intensities indicative of liver fibrosis by decreasing the signal from the non-fibrotic areas where Kupffer cells are present.
Abstract: Our purpose was to validate in vitro a kinetic flow model based on microbubble signal decay curve. Using a 3.5 MHz transducer and phase-inversion (1.8 MHz central transmit frequency), a renal dialysis cartridge oriented vertically was imaged in the transverse plane as 1:1000 dilution of AF0150 was infused at 50, 100, 200, 300 and 400 mL/min. Ten gray-scale images were acquired at each infusion rate using 2.5, 5 and 10 frames/s at 100%, 40%, 15% or 1% of maximum transmit power. Video-intensity measured on each 10 images was fit to a kinetic model using Sigma Plot that yielded microbubble concentration, velocity and destruction per frame. These were correlated with the experimental conditions. At 100% power, video-intensity on the first frame (microbubble concentration at equilibrium) was similar for all flow and frame rates. The model fit the experimental data for all flows at 10 frames/s and for flows lower than 400 and 100 mL/min at 5 frames/s and 2.5 frames/s, respectively. The calculated flow was similar to the experimental flow rates, regardless of technique (r(2) = 0.98). Microbubble fraction destroyed per frame was similar for all flow and frame rates and increased linearly with transmit power (r(2) > 0.98). These results suggest that using appropriate power and frame rate for a given flow rate, estimates of fractional blood volume, flow and destruction fraction can be calculated from the decay curve using 10 frames that can be acquired in 1 to 4 s.
Abstract: PURPOSE: To investigate changes in destruction-replenishment curves (in vitro and in vivo) that result from microbubble destruction in feeding vessels that pass through the imaging plane before microbubbles enter the region of interest (ROI). MATERIALS AND METHODS: During continuous injections of an ultrasonographic contrast agent, nonlinear gray-scale images were obtained in vitro in the longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100, 200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two rabbits (two kidneys). Destruction-replenishment curves were obtained for the dialysis cartridge in ROIs located immediately after the entrance of the microbubbles into the image plane and further from the entrance, after microbubbles had traveled across the complete length of the imaging plane. Replenishment curves were also obtained from ROIs in the rabbit kidneys at the level of segmental arteries, distal interlobar arteries, and the cortex. RESULTS: The ROIs immediately after the entrance of the microbubbles in the image plane of the dialysis cartridge and in the segmental artery of the kidney followed a typical exponential function, A(1 - e-alphat). Early portions of curves obtained in ROIs filled with microbubbles that had already passed through the image plane of the dialysis cartridge or in the renal cortex were not well described by such a function. The shape of the curve and the variations as a function of flow rate can be explained by means of a mathematical model based on indicator-dilution theory. CONCLUSION: When the feeding vessels of an ROI travel across the ultrasound field before they reach the measurement region, the typical shape of the replenishment curve is modified (reduced velocity parameter and plateau).
Abstract: Our goal was to compare two quantification methods of ultrasound contrast agents available in clinical practice [continuous wave Doppler intensity (CWDI) and power Doppler intensity (PWDI)] to the reference technique (radio-frequency analysis) with a simple recirculating flow phantom using a renal dialysis cartridge. Measurements were made at different doses of perflenapent emulsion and BR1. Cineloops of power Doppler images were recorded using a clinically available ultrasound unit (HDI 3000). Simultaneously, integrated backscatter (IBS) was measured by analysis of radiofrequency signals, whereas Doppler signal intensity was measured with a continuous wave Doppler device. A linear relationship was found between CWDI and IBS and between PWDI and IBS when R(2) was calculated for each pair of parameters injection-by-injection. Results are summarized by the average R(2) for all injections between CWDI and IBS (BR1: R(2) = 0.93 +/- 0.05, perflenapent emulsion: R(2) = 0.94 +/- 0.03) and between PWDI and IBS (BR1: R(2) = 0.88 +/- 0.07, perflenapent emulsion: R(2) = 0.79 +/- 0.09). However, for all data obtained from all different injected doses and for both contrast agents, there was considerable variation of CWDI and PWDI values measured for a given value of IBS. In conclusion, for a fixed microbubble population, CWDI and PWDI can be proposed for quantification of USCA. However, their important variations observed at each dose make it difficult to link a single value of PWDI or CWDI or IBS to a single microbubble distribution composition.
Abstract: PURPOSE: To compare thin-section computed tomographic (CT) scans obtained during suspended end expiration with helical CT scans obtained during continuous expiration for the assessment of air trapping. MATERIALS AND METHODS: Forty-nine patients with an airway disease were examined with suspended-end-expiration CT after a 6-8-second expiratory maneuver, which was followed with continuous-expiration CT during a 10-second expiratory maneuver. The extent of expiratory air-trapping areas was calculated by two observers by using a semiquantitative grid score. The relative decrease in attenuation in the areas of air trapping was evaluated with a visual continuous-scale score. RESULTS: Air trapping was noted in 36 and 35 patients with continuous-expiration CT and with suspended-end-inspiration CT, respectively. The extents of and relative attenuation decreases in air-trapping areas in patients with air-trapping areas on at least one expiratory CT scan increased significantly in scans obtained with continuous-expiration CT compared with those obtained with suspended-end-expiration CT, respectively, with mean extent scores of 0.24 +/- 0.20 (SD) and 0.18 +/- 0.20 (paired t test, P: =.001) respectively, and with mean relative contrast decrease scores of 0.35 +/- 0.23 and 0.27 +/- 0.23 (paired t test, P: =.007), respectively. CONCLUSION: When suspended-end-expiration CT images are ambiguous, complementary continuous-expiration CT can be used to improve the conspicuity and apparent extent of air trapping.
Abstract: PURPOSE: To compare the effectiveness and safety of transjugular renal biopsy with those of percutaneous renal biopsy for diagnosis of renal parenchymal disease. MATERIALS AND METHODS: Results and complications of 400 consecutive transjugular renal biopsies performed between 1993 and 1998 with a modified Colapinto transjugular hepatic biopsy system were compared retrospectively with those of 400 percutaneous renal biopsies performed during the same period. Transjugular renal biopsy was associated with 14 cardiac and 35 hepatic biopsies. Number of glomeruli per tissue core, adequacy of tissue core for histopathologic diagnosis, and rate and severity of complications were analyzed. RESULTS: Renal tissue was obtained with percutaneous renal biopsy in 382 (95.5%) of 400 patients and with transjugular renal biopsy in 383 (95.8%) of 400 patients. The mean numbers of intact glomeruli per tissue core with optical microscopy were 11.2 +/- 7.7 (SD) and 9.8 +/- 7.6 for percutaneous renal biopsy and transjugular renal biopsy, respectively. With immunofluorescent microscopy, the mean numbers were 6.4 +/- 5.3 and 4.6 +/- 4.6 for percutaneous renal biopsy and transjugular renal biopsy, respectively. Tissue cores were adequate for histopathologic diagnosis in 98.2% with both techniques. Major complications occurred with transjugular renal biopsy in four patients and with percutaneous renal biopsy in three patients. CONCLUSION: Use of transjugular renal biopsy provides diagnostic yield and safety similar to those of percutaneous renal biopsy and allows multiorgan biopsy during the same procedure. It can be recommended in patients with percutaneous renal biopsy contraindication or failure.
Abstract: Infected abdominal aortic aneurysm is an uncommon but life-threatening disease, especially in case of salmonella infection. Early CT findings should be well known in order to allow immediate diagnosis and accurate management. The authors present an early CT finding of a salmonella infected aneurysm of abdominal aorta in an HIV-infected patient. This pattern consists in a slight-enhancing focal densification of periaortic soft-tissue, while aorta remains of normal size. Within two weeks, infection progressed to the constitution of an infected aneurysm. This CT finding seems to be initial to previously described signs.
Abstract: OBJECTIVE: The objective of this study was to evaluate inter- and intraobserver agreement in the diagnosis of central pulmonary embolism using contrast-enhanced helical CT among observers with variable experience in the interpretation of pulmonary CT angiograms. MATERIALS AND METHODS: Helical CT angiograms of 60 patients clinically suspected of having pulmonary embolism were analyzed retrospectively and independently by two chest radiologists, one cardiovascular radiologist, and three general radiologists. The films were rated a second time by the chest radiologists to assess intraobserver variability. Findings for pulmonary embolism were categorized as positive, negative, or indeterminate at the main, lobar, and segmental pulmonary artery levels. RESULTS: The observers interpreted 19-21 CT angiograms as positive for pulmonary embolism (mean, 19.7) and one to six as indeterminate (mean, 3.2). Agreement occurred among all observers in 50 patients (83.3%), among five observers in six patients (10.0%), among four observers in three patients (5.0%), and among three observers in one patient (1.7%). Interobserver agreement was very good (kappa, .85) for the diagnosis of pulmonary embolism on a per-patient basis. Agreement on a per-artery basis for all arteries was moderate (66%; kappa, .56); for lobar arteries was good (83%; kappa, .75); and for segmental arteries was moderate (57%; kappa, .47). Mean intraobserver agreement on a per-patient basis was very good (93%; kappa, .87). CONCLUSION: Inter- and intraobserver agreement in the diagnosis of pulmonary embolism with helical CT is very good despite a wide variety of experience among radiologists.
Abstract: PURPOSE: To evaluate a lung biopsy technique in which a detachable, 18-gauge, coaxial guide around a central notched stylet is used as a cutting needle. MATERIALS AND METHODS: The records of 89 consecutive patients (41 women, 48 men; aged 21-86 years) who underwent coaxial percutaneous core biopsy of 91 lung lesions that required needle passage through normal lung tissue (mean lesion size, 33.6 mm; range, 9-80 mm) were studied. Detachable, 18-gauge, coaxial automated cutting needles were used. RESULTS: The mean number of needle passes was 2.5 (range, 1-4). All biopsies yielded sufficient tissue for histopathologic (n = 91) and, if necessary, bacteriologic (n = 12) evaluation (mean core length, 5 mm; range, 1-15 mm). Eighty-nine lesions had definitive diagnoses. Seventy-five lesions were proved to be malignant; seventy (93%) could be accurately diagnosed with coaxial percutaneous core biopsy samples. Fourteen lesions were proved to be benign; 10 (71%) were specifically diagnosed with biopsy samples. Among the 91 biopsies, the overall diagnostic accuracy was 88% (80 of 91 lesions). A pneumothorax occurred in 31 cases (34%), three (3%) of which necessitated placement of a chest tube. Postbiopsy hemoptysis occurred and resolved spontaneously in nine cases (10%). CONCLUSION: This technique provides a core biopsy specimen without the need for an on-site cytopathologist during the procedure. It has a high diagnostic accuracy and an acceptable rate of complications.
Abstract: OBJECTIVE: The purpose of our study was to correlate findings on expiratory CT scans with results of pulmonary function tests (PFTs) and to determine whether these techniques may be complementary in assessing airway obstruction. MATERIALS AND METHODS: Seventy-four patients with suspected chronic airway disease and 10 healthy nonsmokers underwent inspiratory and expiratory CT scans and PFTs. An air trapping score, corresponding to the ratio of the cross-sectional air trapping area versus the total cross-sectional lung area on expiratory CT, and a reduction score, representing the change in cross-sectional lung area at inspiration and expiration, were calculated using a quantitative grid. The two scores were then correlated with the results of the PFTs. RESULTS: Expiratory air trapping was seen in 18 (51%) of 35 patients with severe airway obstruction (forced expiratory volume in 1 sec [FEV1]:vital capacity < 80%) (group A), in 21 (72%) of 29 patients with predominantly small airways obstruction (abnormal flow-volume curve and FEV1:vital capacity > or = 80%) (group B1), and in four (40%) of 10 patients with normal PFT results (group B2). Expiratory air trapping was never seen in the 10 healthy subjects. Air trapping scores were 27%, 12%, and 8% for groups A, B1, and B2, respectively, with significant negative correlations with FEV1 (r = -.45), FEV1:vital capacity (r = -.31), and forced expiratory flow at 25% of vital capacity (r = -.57). Reduction scores were 18%, 30%, 35%, and 43%, for the groups A, B1, B2, and the healthy group, respectively, with significant correlations with all the PFT indexes (r = .35 to .66) except total lung capacity. CONCLUSION: Air trapping may permit detection of airway obstruction in patients with clinically suspected chronic airway disease even when PFTs are normal. Furthermore, expiratory CT allows one to calculate a reduction score for a cross-sectional lung area that appears to be better correlated with the degree of airway obstruction measured on PFTs.
Abstract: OBJECTIVE: Our goal was to evaluate dynamic contrast-enhanced subtraction MRI in the diagnosis of isolated clustered calcifications of the breast. MATERIALS AND METHODS: One hundred seventy-two patients underwent surgical biopsy for isolated clustered breast calcifications. Their mammograms showed round (n = 88) or linear/irregular (n = 84) microcalcifications. All patients had a preoperative Gd-DOTA-enhanced subtraction dynamic study. Any early contrast enhancement in the breast parenchyma concomitant with early enhancement of normal vessels was considered positive. RESULTS: Fifty-eight in situ carcinomas, 22 invasive carcinomas, and 92 benign lesions were found at histological analysis. Dynamic MR sequences showed early contrast enhancement in 76 of 80 malignant lesions (sensitivity 95%) and in 45 of 92 benign lesions (specificity 51%). Two invasive and two intraductal carcinomas did not show early contrast enhancement. Three independent observers agreed in rating early contrast enhancement in 143 of 172 lesions. CONCLUSION: Poor specificity limits the diagnostic accuracy of dynamic contrast-enhanced subtraction MRI in distinguishing benign from malignant microcalcifications on mammography.
Abstract: PURPOSE: A retrospective study was performed to assess the role of iodine concentration on the opacification of different vascular compartments of the chest with a nonionic contrast agent (Iopamidol) during routine spiral CT examination. MATERIAL AND METHOD: 105 injected spiral CTs of the chest were studied. 50 examinations were done with Iopamidol 300 (iodine concentration 300 g/L) (I300). 55 examinations were done with Iopamidol 370 (iodine concentration 370 g/L) (I370). A constant 24- g total iodine dose was delivered with no difference in the injected iodine flow rates (respectively 0.6 and 0.55 g/s). Images were scored for opacification success, opacification quality and for artefacts in each vascular, of the chest. RESULTS: There was no statistically significant difference in opacification success or in opacification quality, in each chest vascular compartment between the group receiving I300 and the group receiving I370. Artefact frequencies on the lower part of superior vena cava were however different, 24% and 41.8% respectively. CONCLUSION: For a constant injected iodine flow rate, a moderate increase in iodine concentration, with decreased injection volume and flow rate, had little or no effect on opacification of the aorta and the pulmonary artery. The presence of artefacts on the lower part of the superior vena cava would suggest that the use of lower concentration contrast media would be advisable for specific vena cava examinations.
Abstract: PURPOSE: To compare thin-section computed tomography (CT) and helical CT in the detection and assessment of the extent of bronchiectasis. MATERIALS AND METHODS: Both thin-section and helical CT scans were obtained in 50 consecutive patients with clinical symptoms suggestive of bronchiectasis. Thin-section CT was performed with 1.5-mm collimation and 10-mm intervals, and helical CT was performed with 3-mm collimation and a pitch of 1.6 during a 24-second breath hold. Three observers evaluated 593 segments on CT scans both independently and in consensus. Radiation dose was measured for both techniques. RESULTS: Bronchiectasis was noted in 77 segments (22 patients) on thin-section CT scans compared with 90 segments (26 patients) on helical CT scans. No findings were positive for bronchiectasis on only thin-section CT scans. Interobserver agreement was statistically significantly better (P < .05) in identification of segments that were positive for bronchiectasis on helical CT scans (kappa = 0.87) than on thin-section CT scans (kappa = 0.71). Total skin dose of radiation delivered with helical CT was 3.4 times greater than that delivered with thin-section CT. CONCLUSION: Helical scanning can improve CT depiction of bronchiectasis but with an increase in radiation exposure to the patient. It should be used in patients considered for surgery or for thin-section CT scans that are difficult to interpret.
Abstract: PURPOSE: To correlate histopathologic and magnetic resonance (MR) imaging findings of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Thirty-six women with DCIS underwent preoperative contrast material-enhanced subtraction dynamic MR imaging. Concomitant early contrast enhancement in the breast parenchyma with normal vessels was considered a positive finding. The size and shape of early enhancement were correlated with the size and density packing of ducts involved by DCIS. Tumor angiogenesis in the stroma that surrounded the ducts was evaluated with immunoperoxidase staining. RESULTS: Early contrast enhancement was demonstrated in 34 patients with DCIS but not in two patients with comedo-type DCIS. Tumor angiogenesis was demonstrated in the stroma. The size and morphology of contrast-enhanced lesions significantly correlated with the size (P = .0085) and density packing of ducts involved by DCIS (P = .012). CONCLUSION: Contrast enhancement on dynamic MR images of DCIS may be due to the presence of tumor angiogenesis in the stroma.
Abstract: Standard chest radiographs have been shown to be insensitive for the diagnosis of morphologic abnormalities of airways. Computed tomography is the most sensitive and specific investigation to diagnose emphysema. However, as emphysema may be missed on computed tomography, this investigation cannot be used to definitely rule out the diagnosis. Computed tomography may contribute to the investigation of bronchiolitis, and it is now considered as the gold standard for establishing the diagnosis of bronchiectasis. Imaging may contribute to identify complications such as bronchopulmonary infection, pulmonary hypertension, pneumothorax, cancer of the lung, compressive bullae, and pulmonary embolism.
Abstract: AIM: To assess the validity and the interest to health of systematic herniography in cases of unilateral inguinal hernia in children under two years of age. METHOD: Decision theory was used to assess the effect of herniography on individual health by estimating gonadic benefit and establishing a benefit-risk ratio, and on collective health by the use of cost-effectiveness analysis. RESULTS: a decision tree and algorithms were developed. DISCUSSION: Decision analysis is used in complex medical decision making, clarifying choices and subdividing a problem into several more manageable sub-problems. The threshold approach pinpoints factors requiring more information.
Abstract: PURPOSE: To determine the accuracy of contrast material-enhanced subtraction dynamic magnetic resonance (MR) imaging in the diagnosis of nonpalpable breast tumors. MATERIALS AND METHODS: One hundred forty-three patients underwent surgical biopsy of a nonpalpable breast lesion. Their mammograms showed microcalcifications (n = 80), opacity (n = 52), architectural distortion (n = 10), or asymmetric density (n = 1). All patients underwent a preoperative gadolinium tetraazacyclododecanetetraacetic acid-enhanced subtraction dynamic study. Any early contrast enhancement in the breast parenchyma was considered pathologic. RESULTS: At histologic analysis, 27 intraductal carcinomas, 37 invasive carcinomas, and 79 benign lesions were found. Dynamic MR studies showed early contrast enhancement in 61 of 64 breast cancers (sensitivity, 95%) and in 37 of 79 benign lesions (specificity, 53%). Two invasive lobular carcinomas and one tubular carcinoma showed no early contrast enhancement. CONCLUSION: Subtraction dynamic MR imaging may be helpful to rule out malignancy in nonpalpable breast tumors.
