Center for Biomaterials and Tissue Engineering & Electronic Engineering Department Universitat Politècnica de València Cami de Vera, s/n ES46022 Valencia Spain
Abstract: Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that is organized into fibrillar networks by cells through an integrin-mediated process that involves contractile forces. This assembly allows for the unfolding of the FN molecule, exposing cryptic domains that are not available in the native globular FN structure and activating intracellular signalling complexes. However, organization of FN into a physiological fibrillar network upon adsorption on a material surface has not been observed. Here we demonstrate cell-free, material-induced FN fibrillogenesis into a biological matrix with enhanced cellular activities. We found that simple FN adsorption onto poly(ethyl acrylate) surfaces, but not control polymers, triggered FN organization into a fibrillar network via interactions in the amino-terminal 70 kDa fragment, which is involved in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules and even type I collagen. Our results demonstrate that molecular assembly of FN can take place at the material interface, giving rise to a physiological protein network similar to fibrillar matrices assembled by cells. This research identifies material surfaces that trigger the organization of extracellular matrix proteins into biological active fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials.
Abstract: Pharmacoinvasive strategy represents an attractive alternative to primary angioplasty. Using cardiovascular magnetic resonance imaging we compared the left ventricular outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction.
Abstract: This article introduces a novel method named "Parallel Imaging and Noquist in Tandem" (PINOT) for accelerated image acquisition of cine cardiac magnetic resonance imaging. This method combines two prior information formalisms, the SPACE-RIP implementation of parallel imaging and the Noquist method for reduced-data image reconstruction with prior knowledge of static and dynamic regions in the field of view. The general theory is presented, and supported by results from experiments using time-resolved two-dimensional simulation data and retrospectively sub-sampled magnetic resonance imaging data with acceleration factors around 4. A signal-to-noise ratio analysis and a comparison study with TSENSE and k-t SENSE show that PINOT performs favorably in preserving edge detail, at a cost in signal-to-noise ratio and computational complexity.
Abstract: It is known that surface nanotopography influences cell adhesion and differentiation. Our aim is to analyze the effect of nanoscale topography on fibronectin adsorption and, afterwards, on cell adhesion in order to rationalize the cell-material interaction by focusing on the state of the intermediate layer of adsorbed fibronectin at the material interphase.
Abstract: The cell-material interaction is a complex bi-directional and dynamic process that mimics to a certain extent the natural interactions of cells with the extracellular matrix. Cells tend to adhere and rearrange adsorbed extracellular matrix (ECM) proteins on the material surface in a fibril-like pattern. Afterwards, the ECM undergoes proteolytic degradation, which is a mechanism for the removal of the excess ECM usually approximated with remodeling. ECM remodeling is a dynamic process that consists of two opposite events: assembly and degradation.
Abstract: Bone Marrow mesenchymal stem cells can be induced to differentiate into osteoblasts to regenerate damaged bone tissue using tissue engineering techniques. In this study, we examine the use of chitosan scaffolds with double pore structure prepared by an innovative method that combines freeze gelation (that produces micropores) and particle leaching out technique (that produces interconnected spherical macropores) seeking to enhance the osteogenic differentiation of goat bone marrow stromal cells (GBMSCs). The double pore architecture of the scaffold was characterized by scanning electron microscopy (SEM), microcomputed tomography and confocal laser scanning microscopy. The obtained hierarchical pore structure allowed very efficient seeding of GBMSCs that are able to occupy the whole volume of the scaffold, showing good adhesion and proliferation. GBMSCs were differentiated into osteoblasts as indicated by alkaline phosphatase activity and osteocalcin expression. The results of this study demonstrate that chitosan scaffold may be promising biomaterial for bone regeneration.
Abstract: OBJECTIVE: To estimate the dynamic relations between cerebrospinal fluid (CSF) and blood in the cerebral and spinal subarachnoid spaces and in the ventricles by quantifying phase contrast magnetic resonance imaging (MRI). MATERIAL AND METHODS: We analyzed 15 healthy volunteers during the same time of day and using the same magnetic field strength (3T). Each study consisted of four phase contrast sequences: two to calculate the CSF (aqueduct of Sylvius and the C2-C3 perimedullary space) and two to calculate the blood flow (internal carotid and vertebral arteries, superior sagittal sinus, and straight sinus). We calculated the amplitude parameters (systolic volume, mean flow, pulsatility and compliance indexes, absolute pressure gradient, and ratio of CSF volume per cycle) and temporal parameters (delays respect to arterial flow). RESULTS: With respect to the input of arterial blood, the displacement of venous blood (22% and 38% of the cardiac cycle in the straight sinus and superior sagittal sinus, respectively) and of CSF (12% and 25% of the cardiac cycle in the C2-C3 perimedullary space and in the aqueduct of Sylvius, respectively) show the distribution of the pulsatility of the intracranial fluids. We calculated the indexes of compliance of the encephalic and medullary compartments in normal subjects. CONCLUSIONS: It is possible to quantitatively describe the dynamic relations between intracranial fluids and infer the elastic behavior of the brain and spinal canal by using flow velocity maps obtained with phase contrast MRI.
Abstract: PURPOSE: In vivo two-dimensional (2D) fractal dimension (D2D) analysis of the cancellous bone at 1.5 T has been related to bone structural complexity and shown to be a potential imaging-based biomarker for osteoporosis. The objectives of this study were to assess at 3 T the in vivo feasibility of three-dimensional (3D) bone fractal dimension (D3D) analysis, analyze the relationship of D2D and D3D with osteoporosis, and investigate the relationship of D3D with spinal bone mineral density (BMD). METHODS: A total of 24 female subjects (67 +/- 7 yr old, mean +/- SD) was included in this study. The cohort consisted of 12 healthy volunteers and 12 patients with osteoporosis. MR image acquisitions were performed in the nondominant metaphysis of the distal radius with a 3 T MR scanner and an isotropic resolution of 180 microm. After segmentation and structural reconstruction, 2D and 3D box-counting algorithms were applied to calculate the fractal complexity of the cancellous bone. D2D and D3D values were compared between patients with osteoporosis and healthy subjects, and their relationship with radius BV/TV and spinal BMD was also assessed. RESULTS: Significant differences between healthy subjects and patients with osteoporosis were obtained for D3D (p < 0.001), with less differentiation for D2D (p = 0.04). The relationship between fractal dimension and BMD was not significant (r = 0.43, p = 0.16 and r = 0.23, p = 0.48, for D2D and D3D, respectively). CONCLUSIONS: The feasibility of trabecular bone D3D calculations at 3 T and the relationship of both D2D and D3D parameters with osteoporosis were demonstrated, with a better differentiation for the 3D method. Furthermore, the D3D parameter has probably a different nature of information regarding the trabecular bone status not directly explained by BMD alone. Future studies with subjects with osteopenia and larger sample sizes are warranted to further establish the potential of D2D and D3D in the study of osteoporosis.
Abstract: Phase separation of PLLA/PS (50/50, w/w) solutions during a spin-casting process gives rise to well-defined nanotopographies of 14, 29 and 45 nm deep pits depending on the concentration of the solution. Their influence on the biological activity of fibronectin (FN) was investigated. FN adsorption was quantified by radiolabelling the protein. The amount of adsorbed FN was higher on the 14 nm deep pit nanotopography than on the other two surfaces. FN distribution between valleys and peaks was investigated by AFM combined with image analysis. FN tends to adsorb preferentially on the valleys of the nanotopography only for the 14 nm system and when adsorbed from solutions of concentration lower than 10 microg/ml. Higher concentration of the FN solution leads to evenly distribution of the protein throughout the surface; moreover, there is no difference in the distribution of the protein between valleys and peaks for the other two systems (29 and 45 nm) irrespective of the concentration of the FN solution. The biological activity of the adsorbed protein layer was assessed by investigating MC3T3 osteoblast-like cells adhesion, FN reorganisation and late matrix formation on the different substrates. Even if initial cell adhesion is excellent for every substrate, the size of the focal adhesion plaques increases as the size of the pits in the nanotopography does. This is correlated to FN reorganisation, which only takes places on the 29 and 45 nm deep pits surfaces, where enhanced late matrix production was also found.
Abstract: OBJECTIVE: To establish normal values for the different parameters that characterize the cerebrospinal fluid (CSF) flow dynamics in the aqueduct of Sylvius (velocity, flow, volume per cycle, and CSF production) obtained from phase-contrast MR images using a reliable and reproducible post-processing method. The optimized semiautomatic method eliminates interobserver variability and corrects errors due to low amplitude movements, aliasing, and the partial volume effect. MATERIAL AND METHODS: We studied 42 healthy subjects without neurological or cerebrovascular disease or disturbances in CSF dynamics. Images were acquired on a 1.5 T MR scanner using a phase-contrast sequence. All images were acquired during the same time frame (14:00 to 18:00) to avoid circadian influences. RESULTS: we obtained normal values for each of the parameters that characterize CSF dynamics in the aqueduct (maximum diastolic and systolic velocity, mean velocity, maximum diastolic and systolic flow, mean flow, production rate, and stroke volume). Although trends were noted, neither sex nor age (< 25, 26-50, >51 years old) had a statistically significant effect on any parameter (p> or =0.05). DISCUSSION: Although measurements of CSF flow dynamics parameter are sensitive to various factors (temporal and spatial resolutions of the MR sequence, circadian rhythms, age, sex, and MR equipment manufacturer), an optimized post-processing method enables reliable and reproducible values and ranges for normal subjects to be established.
Abstract: This article reviews the regulations in force about the exposure of workers to the electromagnetic fields generated by magnetic resonance imaging (MRI) and evaluates the impact of European Directive 2004/40/EC on the daily use of MRI. We provide a detailed review of the safety criteria stipulated in the International Commission on Non-Ionizing Radiation Protection, in Spanish Royal Decree 1066/2001, and in European Directive 2004/40/EC about exposure to electromagnetic fields. In the case of European Directive 2004/40/EC, the European Union (EU) has introduced a law without adequately evaluating its repercussions. In response to alarms sounded by the radiological and general medical communities, the EU has decided to delay implementation of the Directive. Although the implementation of Directive 2004/40/ EC has been postponed until April 30, 2012, it remains in force. There remains the hope that the Directive will be reconsidered during this interval and that MRI workers will be exempt.
Abstract: OBJECTIVE: To define normal values of MRI parameters related to cardiac morphology, function, perfusion, and delayed enhancement of the left ventricle and to analyze differences based on age and sex. MATERIAL AND METHODS: We used 1.5T and 3T MRI scanners to analyze 18 healthy subjects ranging in age from 15 to 77 years old. Dedicated image processing software (Cardio-MR, View Forum, Philips Medical Systems) was used to evaluate morphological and functional parameters (end-diastolic and end-systolic volume, stroke volume, ejection fraction, cardiac output, wall mass, wall thickness, wall thickening, wall motion), perfusion parameters (relative maximum upslope, relative maximum enhancement), and delayed enhancement (percentage of late hyperenhancement). Student's t-test was used for statistical analyses. RESULTS: Sex differences were observed: end-diastolic and end-systolic volumes, stroke volume, and wall mass were significantly higher in men and the ejection fraction was significantly larger in women. Healthy subjects over 45 years of age had significantly greater wall thickness. CONCLUSION: We report cardiac MRI reference values for morphological, functional, perfusion, and delayed enhancement parameters. Sex and age should be taken into account as important variables related to some of these parameters.
Abstract: The influence of surface chemistry-substrates with controlled surface density of -OH groups-on fibronectin (FN) conformation and distribution is directly observed by atomic force microscopy (AFM). FN fibrillogenesis, which is known to be a process triggered by interaction with integrins, is shown in our case to be induced by the substrate (in absence of cells), which is able to enhance FN-FN interactions leading to the formation of a protein network on the material surface. This phenomenon depends both on surface chemistry and protein concentration. The level of the FN fibrillogenesis was quantified by calculating the fractal dimension of the adsorbed protein from image analysis of the AFM results. The total amount of adsorbed FN is obtained by making use of a methodology that employs Western blotting combined with image analysis of the corresponding protein bands, with the lowest sensitivity threshold equal to 15 ng of adsorbed protein. Further, FN adsorption is correlated to human osteoblast adhesion through morphology and actin cytoskeleton formation. Actin polymerization is in need of the formation of the protein network on the substrate's surface. Cell morphology is more rounded (as quantified by calculating the circularity of the cells by image analysis) when the degree of FN fibrillogenesis on the substrate is lower.
Abstract: To evaluate the response to treatment with cabergoline for ovarian hyperstimulation syndrome (OHS) using mono- and bi-compartmental MRI models.
Abstract: INTRODUCTION AND OBJECTIVES: Dipyridamole stress perfusion cardiovascular magnetic resonance (CMR) is used to detect coronary artery disease (CAD). However, few data are available on the diagnostic value of the systolic dysfunction induced by dipyridamole. This study investigated whether the induction of systolic dysfunction supplements the diagnostic information provided by perfusion imaging in the detection of CAD. METHODS: Overall, 166 patients underwent dipyridamole CMR and quantitative coronary angiography, with CAD being defined as a stenosis > or =70%. Systolic dysfunction at rest, systolic dysfunction with dipyridamole, induced systolic dysfunction, and stress first-pass perfussion deficit (PD) and delayed enhancement were quantified. RESULTS: In the multivariate analysis, PD (hazard ratio [HR]=1.6; 95% confidence interval [CI], 1.33-1.91;P< .0001) and induced systolic dysfunction (OR=1.8; 95% CI, 1.18-2.28; P< .007) were independently associated with CAD and had a sensitivity and specificity of 92% and 62% and 43% and 96%, respectively. Patients were categorized as having no ischemia (Group 1), PD but no induced systolic dysfunction (Group 2), or induced systolic dysfunction irrespective of PD (Group 3). In Group 3, the prevalence of CAD was higher than in Group 1 or 2 (96% vs. 22% and 79%, respectively; P=.001) and the risk of CAD was two-fold higher than in Group 2 (OR=2.34; 95% CI, 1.07-5.13; P=.034). Compared with Group 2, more hypoperfused segments were observed in Group 3 (6.2+/-2.6 vs. 7.4+/-3.4; P=.044), and more diseased vessels (1.4+/-1.0 vs. 1.8+/-0.9; P=.036). Adding induced systolic dysfunction to perfusion and clinical data improved the multivariate model's C-statistic for predicting CAD (0.81 vs. 0.87; P=.02). CONCLUSIONS: Combining induced systolic dysfunction with perfusion imaging increases the diagnostic accuracy of detecting CAD and enables patients with severe ischemia and a high probability of CAD to be identified.
Abstract: OBJECTIVE: To determine the prognostic and therapeutic implications of stress perfusion cardiovascular magnetic resonance (CMR) on the basis of the ischaemic cascade. SETTING: Single centre study in a teaching hospital in Spain. PATIENTS: Dipyridamole stress CMR was performed on 601 patients with ischaemic chest pain and known or suspected coronary artery disease. On the basis of the ischaemic cascade, patients were categorised in C1 (no evidence of ischaemia, n = 354), C2 (isolated perfusion deficit at stress first-pass perfusion imaging, n = 181) and C3 (simultaneous perfusion deficit and inducible wall motion abnormalities, n = 66). CMR-related revascularisation (n = 102, 17%) was defined as the procedure prompted by the CMR results and carried out within the next three months. RESULTS: During a median follow-up of 553 days, 69 major adverse cardiac events (MACE), including 21 cardiac deaths, 14 non-fatal myocardial infarctions and 34 admissions for unstable angina with documented abnormal angiography were detected. In non-revascularised patients (n = 499), the MACE rate was 4% (14/340) in C1, 20% (26/128) in C2 and 39% (12/31) in C3 (adjusted p value = 0.004 vs C2 and <0.001 vs C1). CMR-related revascularisation had neutral effects in C2 (20% vs 19%, 1.1 (0.5 to 2.4), p = 0.7) but independently reduced the risk of MACE in C3 (39% vs 11%, 0.2 (0.1 to 0.7), p = 0.01). CONCLUSIONS: Dypiridamole stress CMR is able to stratify risk on the basis of the ischaemic cascade. A small group of patients with severe ischaemia-simultaneous perfusion deficit and inducible wall motion abnormalities-are at the highest risk and benefit most from MACE reduction due to revascularisation.
Abstract: Detailed knowledge of the porous architecture of synthetic scaffolds for tissue engineering, their mechanical properties, and their interrelationship was obtained in a nondestructive manner. Image analysis of microcomputed tomography (microCT) sections of different scaffolds was done. The three-dimensional (3D) reconstruction of the scaffold allows one to quantify scaffold porosity, including pore size, pore distribution, and struts' thickness. The porous morphology and porosity as calculated from microCT by image analysis agrees with that obtained experimentally by scanning electron microscopy and physically measured porosity, respectively. Furthermore, the mechanical properties of the scaffold were evaluated by making use of finite element modeling (FEM) in which the compression stress-strain test is simulated on the 3D structure reconstructed from the microCT sections. Elastic modulus as calculated from FEM is in agreement with those obtained from the stress-strain experimental test. The method was applied on qualitatively different porous structures (interconnected channels and spheres) with different chemical compositions (that lead to different elastic modulus of the base material) suitable for tissue regeneration. The elastic properties of the constructs are explained on the basis of the FEM model that supports the main mechanical conclusion of the experimental results: the elastic modulus does not depend on the geometric characteristics of the pore (pore size, interconnection throat size) but only on the total porosity of the scaffold.
Abstract: The influence of the surface fraction of OH groups on fibrinogen (FG) adsorption is investigated in copolymers of ethyl acrylate and hydroxy ethylacrylate. The amount of adsorbed FG, quantified by western-blotting combined with image analysis of the corresponding bands, decreases as the hydrophilicity of the substrate increases. The influence of substrate wettability on FG conformation and distribution is observed by atomic force microscopy (AFM). The most hydrophobic substrate promotes FG fibrillogenesis, which leads to a fibrin-like appearance in the absence of any thrombin. The degree of FG interconnection was quantified by calculating the fractal dimension of the adsorbed protein from image analysis of the AFM results. The biological activity of the adsorbed FG is correlated to cell adhesion on FG-coated substrates.
Abstract: OBJECTIVE: The morphological analysis of trabecular bone of the distal epiphysis of the radius and its three-dimensional representation allow an adequate evaluation of bone quality. We analyzed trabecular bone morphology and its three-dimensional modeling with high resolution magnetic resonance imaging (MRI) to determine the parameters that provide useful information about bone condition. MATERIAL AND METHODS: All data were acquired using 3D T1-weighted gradient-echo sequences in a 3-Tesla MRI scanner. The mathematical algorithms required to study trabecular bone structure were developed in a Matlab environment on a personal computer. A total of 16 healthy subjects (10 women and 6 men; aged 23 to 54 years, mean 36+/-10 years) were studied. No significant differences were found between women (mean age 39+/-12, range: 23-54 years) and men (mean age 33+/-6, range: 25-42) (p = 0.285). Healthy subjects were recruited from among normal subjects studied to assess the ligaments of the wrist. The morphological parameters analyzed were trabecular volume, mean trabecular thickness, mean trabecular separation, and trabecular index. RESULTS: The morphological parameters that were useful in the evaluation of bone quality were trabecular volume (women: 23.22+/-1.78%; men: 27.49+/-1.30%), trabecular thickness (women: 0.1901+/-0.0014 mm; men: 0.1935+/-0.0014 mm), trabecular separation (women: 0.8332+/-0.0440 mm; men: 0.7697+/-0.0258 mm), and the number of trabeculae (women: 1.2215+/-0.0920 mm-1; men: 1.4207+/-0.0640 mm-1). Statistically significant differences between men and women were found for all the parameters analyzed; no significant differences were found in relation with age in this series. CONCLUSIONS: High resolution MRI enabled the morphological characterization of the trabecular bone structure; this represents an advance in the detection of biomarkers for disease.
Abstract: OBJECTIVE: The purpose of this study was to investigate the in vivo morphologic and elastic parameters of trabecular bone with high-resolution 3-T MRI in a healthy reference population. SUBJECTS AND METHODS: A series of wrist MR images were acquired with high-spatial-resolution (180 mum) isotropic voxels from 40 subjects without reported bone disease. After image postprocessing, the bone volume-to-total volume ratio, trabecular thickness, trabecular separation, and trabecular number were calculated in the morphologic analysis. Trabecular bone was mechanically simulated using the finite-element method to calculate the apparent elastic modulus parameter. The relationship between morphologic and mechanical parameters was studied. The influence of the analyzed bone volume was also investigated. RESULTS: Statistically significant sex influences were found on the bone volume-to-total volume ratio (p = 0.003), trabecular thickness (p = 0.02), and apparent elastic modulus (p = 0.01); these parameters were lower in women. However, trends were found only on trabecular separation (p = 0.06) and trabecular number (p = 0.07). Age had no statistically significant influence in any morphologic (bone volume-to-total volume ratio, r = -0.24, p = 0.13; trabecular thickness, r = -0.03, p = 0.88; trabecular separation, r = 0.12, p = 0.47; and trabecular number, r = -0.23, p = 0.16) or elastic (apparent elastic modulus, r = -0.18, p = 0.26) parameter. A statistically significant relationship between apparent elastic modulus and the square of bone volume-to-total volume ratio was found (r = 0.968, p < 0.001). This association was not seen (r = 0.185, p = 0.25) and apparent elastic modulus results were considerably different (p < 0.001) if the volume of analyzed bone was reduced. CONCLUSION: We found that bone volume-to-total volume ratio, trabecular thickness, and apparent elastic modulus are parameters significantly influenced by sex. Apparent elastic modulus results show a relationship with bone volume-to-total volume ratio. Trabecular bone volume should be maximized for an appropriate mechanical analysis.
Abstract: Suicidal attempts are relatively frequent and clinically relevant in patients with schizophrenia. Recent studies have found gray matter differences in suicidal and non-suicidal depressive patients. However, no previous neuroimaging study has investigated possible structural abnormalities associated to suicidal behaviors in patients with schizophrenia. A whole-brain magnetic resonance voxel-based morphometric examination was performed on 37 male patients meeting the DSM-IV criteria for schizophrenia. Thirteen (35.14%) patients had attempted suicide. A non-parametric permutation test was computed to perform the comparability between groups. An analysis of covariance (AnCova) model was constructed with a statistical threshold of p<0.05 corrected for multiple comparisons. After controlling for age and severity of illness, results showed significant gray matter density reduction in left superior temporal lobe (p=0.03) and left orbitofrontal cortex (p=0.04) in patients who had attempted suicide when comparing with non-suicidal patients. Although sample size limitations and potential clinical heterogeneity preclude definitive conclusions, these data point to structural differences in key cerebral areas. Neuroimaging studies are necessary to expand our knowledge of biological mechanisms underlying suicide in schizophrenia.
Abstract: Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls. Patients were evaluated using the PSYRATS scale for auditory hallucinations. Reductions of gray matter concentration in patients to controls were observed in bilateral insula, bilateral superior temporal gyri and left amygdala. In addition, specific relationships between left inferior frontal and right postcentral gyri reductions and the severity of auditory hallucinations were observed. All these areas might be implicated in the genesis and/or persistence of auditory hallucinations through specific mechanisms. Precise morphological abnormalities may help to define reliable MR-VBM biomarkers for the genesis and persistence of auditory hallucinations.
Abstract: PURPOSE: To study the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the patellar cartilage under normal and pathological conditions. MATERIALS AND METHODS: DCE-MRI was obtained in 22 cases. There were 17 patients with degenerative patellar conditions (eight with chondromalacia and nine with osteoarthritis) and five normal subjects. The cartilage pharmacokinetic parameters of K(trans) (vascular permeability), k(ep) (extraction ratio), upsilon(e) (extravascular extracellular space [EES] volume fraction), and upsilon(p) (intravascular space volume fraction) were extracted. RESULTS: Statistically significant differences were observed between the different groups (normal cartilage, chondromalacia and osteoarthritis) for K(trans) and upsilon(e). K(trans) values were (mean +/- SD) 1.06 +/- 0.62, 11.97 +/- 8.91, and 21.21 +/- 16.03 mL x minute(-1) x 100 mL(-1) (P < 0.02), respectively; and upsilon(e) values were 0.71 +/- 0.69, 3.59 +/- 2.21, and 10.51 +/- 8.20% (P < 0.002). Reproducibility of the pharmacokinetic calculations was assessed with a second set of analyses of 10 random cases one week after the first analysis, showing a test-retest root mean square (RMS) coefficient of variation of 9.78% for K(trans) and 14.72% for upsilon(e). CONCLUSION: The vascular permeability and EES fraction of cartilage increases with the severity of the degeneration. Pharmacokinetic models allow to study the vascular properties of the cartilage and may have applications as a surrogate index in longitudinal studies to quantify the evolution of drug trials.
Abstract: Neuroimaging studies of emotional response in schizophrenia have mainly used visual (faces) paradigms and shown globally reduced brain activity. None of these studies have used an auditory paradigm. Our principal aim is to evaluate the emotional response of patients with schizophrenia to neutral and emotional words. An auditory emotional paradigm based on the most frequent words heard by psychotic patients with auditory hallucinations was designed. This paradigm was applied to evaluate cerebral activation with functional magnetic resonance imaging (fMRI) in 11 patients with schizophrenia with persistent hallucinations and 10 healthy subjects. We found a clear enhanced activity of the frontal lobe, temporal cortex, insula, cingulate, and amygdala (mainly right side) in patients when hearing emotional words in comparison with controls. Our findings are consistent with other studies suggesting a relevant role for emotional response in the pathogenesis and treatment of auditory hallucinations.
Abstract: In this study, a method to segment ovary Magnetic Resonance (MR) images and distinguish healthy tissue from cysts has been described. Through the application of independent component analysis (ICA) to a set of perfusion MR images it was possible to extract the output independent components and their corresponding signal-time curves. After examining and analyzing this result, a polynomial approach was computed to represent the main features of each curve, and automated particular selection of independent components was obtained by applying a Bayesian information criterion able to show the most relevant components. The results shown in this work permit to conclude that the independent components with a step-like signal-time curve allow to distinguish healthy tissue from cysts, thus, giving very promising results for the application of ICA to ovary tissue segmentation of perfusion MR images.
Abstract: As Bone Mineral Density has been demonstrated to be insufficient to elaborate a correct diagnosis of bone diseases such as osteoporosis, a new software tool called EsTra has been developed in order to estimate the most significant structural parameters of trabecular bone microarchitecture. In EsTra, different techniques as automated segmentation, snakes, filtering, skeletonization, voxel classification and three-dimensional reconstruction are applied to Magnetic Resonance images of distal radius and ulna. A microarchitectural study is also carried out from three different viewpoints involving morphological, topological and fractal analysis. Results can be exported to a database to help the research of the disease and a clinical report is elaborated containing the most significant parameters obtained from the analysis.
Abstract: Atrial tachyarrhythmias are a very common cardiovascular disease in clinical practice with an incidence that doubles with each advancing decade. A key issue to understand their pathophysiological mechanisms is the analysis and interpretation of atrial electrograms (AEG). To properly study these signals, ventricular artifacts have to be removed from the AEG. In this work, a new application of independent component analysis (ICA) to the AEG is presented where ventricular artifacts are removed from atrial recordings making use of only one reference lead. Therefore the technique is suitable when multi-lead recordings are unavailable as in atrial implantable cardioverter-defibrilators. The methodology has been compared with traditional techniques on a database of 20 patients. Performance was evaluated through atrial waveform similarity (S) and ventricular activity reduction (V D R) as a function of atrial rhythm regularity on a beat-by-beat basis. When the atrial tachyarrhythmia is quite regular, results show that ICA preserves the atrial waveform better than the other methods (median S = 99:64%) whereas maintaining ventricular reduction (median VDR = 6:32dB).
Abstract: The analysis of the surface electrocardiogram (ECG) is the most extended noninvasive technique in medical diagnosis of atrial fibrillation (AF). In order to use the ECG as a tool for the analysis of AF, we need to separate the atrial activity (AA) from other cardioelectric signals. In this matter, statistical signal processing techniques, like blind source separation (BSS), are able to perform a multilead statistical analysis with the aim to obtain the AA. Linear BSS techniques can be divided in two groups depending on the mixing model: algorithms where instantaneous mixing of sources is assumed, and convolutive BSS (CBSS) algorithms. In this work, a comparison of performance between one relevant CBSS algorithm, namely Infomax, and one of the most effective independent component analysis (ICA) algorithms, namely FastICA, is developed. To carry out the study, pseudoreal AF ECGs have been synthesized by adding fibrillation activity to normal sinus rhythm. The algorithm performances are expressed by two indexes: the signal to interference ratio (SIRAA) and the cross-correlation (RAA) between the original and the estimated AA. Results empirically prove that the instantaneous mixing model is the one that obtains the best results in the AA extraction, given that the mean SIRAA obtained by the FastICA algorithm (37.6 +/- 17.0 dB) is higher than the main SIRAA obtained by Infomax (28.5 +/- 14.2 dB). Also the RAA obtained by FastICA (0.92 +/- 0.13) is higher than the one obtained by Infomax (0.78 +/- 0.16).
Abstract: In order to help the assessment of trabecular bone diseases and complement Dual X-Ray Absorptiometry (DXA) in diagnosis process, it is needed an accurate mechanical characterization of trabecular bone structure to estimate the risk of fracture and evaluate micro-architecture deterioration. As Finite Element modeling has become a well-established method for analysis of complex structures, an algorithm has been developed to build a Finite Element mesh from three-dimensional reconstruction information in voxels. Generated mesh is loaded in a Finite Element analysis software in order to simulate micro-architecture mechanical behavior under compression conditions. Most part of related researches have been based on ex vivo micro-Computed Tomography (microCT) scans. This study uses three-dimensional trabecular bone reconstructions from high resolution Magnetic Resonance images acquired in vivo.
Abstract: INTRODUCTION: A combination of good clinical selection with reliable quantification of diverse parameters that characterize the dynamics of cerebrospinal fluid (CSF) flow from phase-contrast magnetic resonance imaging may identify patients with idiopathic normal pressure hydrocephalus (NPH). MATERIAL AND METHODS: We have carried out a quantitative analysis of 38 subjects (19 healthy subjects and 19 patients with suspected idiopathic NPH). The images were acquired using a 1.5 T MR unit with a phase-contrast sequence in an oblique-transversal plane perpendicular to the Sylvius aqueduct codified to 20 cm/s and with 27 observations per cardiac cycle by means of retrospective synchronization. The area was defined to half the height of the peak velocity, to maximize accuracy. Parameters quantified were mean flow, maximum systolic and diastolic flow, maximum systolic and diastolic velocity, mean velocity, CSF production and stroke volume. RESULTS: All the parameters measured showed a significant difference (ANOVA: p<or=0,05) between controls and patient except for the maximum systolic velocity (p=0.17). It was observed in the discriminant analysis that the two groups (controls and patients) were classified correctly in 92.1% with the use of the maximum systolic flow and CSF production. CONCLUSIONS: Semiautomatic quantification of the dynamics of CSF by means of MRI differentiates patients with hyperdynamic state from the control subjects, with significant differences that can be used to classify idiopathic HNP.
Abstract: PURPOSE: To prospectively evaluate if functional magnetic resonance (MR) imaging abnormalities associated with auditory emotional stimuli coexist with focal brain reductions in schizophrenic patients with chronic auditory hallucinations. MATERIALS AND METHODS: Institutional review board approval was obtained and all participants gave written informed consent. Twenty-one right-handed male patients with schizophrenia and persistent hallucinations (started to hear hallucinations at a mean age of 23 years +/- 10, with 15 years +/- 8 of mean illness duration) and 10 healthy paired participants (same ethnic group [white], age, and education level [secondary school]) were studied. Functional echo-planar T2*-weighted (after both emotional and neutral auditory stimulation) and morphometric three-dimensional gradient-recalled echo T1-weighted MR images were analyzed using Statistical Parametric Mapping (SPM2) software. Brain activation images were extracted by subtracting those with emotional from nonemotional words. Anatomic differences were explored by optimized voxel-based morphometry. The functional and morphometric MR images were overlaid to depict voxels statistically reported by both techniques. A coincidence map was generated by multiplying the emotional subtracted functional MR and volume decrement morphometric maps. Statistical analysis used the general linear model, Student t tests, random effects analyses, and analysis of covariance with a correction for multiple comparisons following the false discovery rate method. RESULTS: Large coinciding brain clusters (P < .005) were found in the left and right middle temporal and superior temporal gyri. Smaller coinciding clusters were found in the left posterior and right anterior cingular gyri, left inferior frontal gyrus, and middle occipital gyrus. CONCLUSION: The middle and superior temporal and the cingular gyri are closely related to the abnormal neural network involved in the auditory emotional dysfunction seen in schizophrenic patients.
Abstract: Intravascular ultrasound (IVUS) imaging is used along with X-ray coronary angiography to detect vessel pathologies. Manual analysis of IVUS images is slow and time-consuming and it is not feasible for clinical purposes. A semi-automated method is proposed to generate 3D reconstructions from IVUS video sequences, so that a fast diagnose can be easily done, quantifying plaque length and severity as well as plaque volume of the vessels under study. The methodology described in this work has four steps: a pre-processing of IVUS images, a segmentation of media-adventitia contour, a detection of intima and plaque and a 3D reconstruction of the vessel. Preprocessing is intended to remove noise from the images without blurring the edges. Segmentation of media-adventitia contour is achieved using active contours (snakes). In particular, we use the gradient vector flow (GVF) as external force for the snakes. The detection of lumen border is obtained taking into account gray-level information of the inner part of the previously detected contours. A knowledge-based approach is used to determine which level of gray corresponds statistically to the different regions of interest: intima, plaque and lumen. The catheter region is automatically discarded. An estimate of plaque type is also given. Finally, 3D reconstruction of all detected regions is made. The suitability of this methodology has been verified for the analysis and visualization of plaque length, stenosis severity, automatic detection of the most problematic regions, calculus of plaque volumes and a preliminary estimation of plaque type obtaining for automatic measures of lumen and vessel area an average error smaller than 1mm(2) (equivalent aproximately to 10% of the average measure), for calculus of plaque and lumen volume errors smaller than 0.5mm(3) (equivalent approximately to 20% of the average measure) and for plaque type estimates a mismatch of less than 8% in the analysed frames.
Abstract: OBJECTIVE: Quantification of the cerebrospinal fluid (CSF) flow through the aqueduct of Sylvius by means of magnetic resonance imaging (MRI) is subject to interobserver variability due to the region of interest (ROI) selection. Our objective is to develop a semiautomatic measurement method to achieve reproducible quantitative analysis of CSF flow rate and stroke volume. MATERIAL AND METHODS: MR examinations were performed using a 1.5 T scanner with a phase contrast sequence (velocity encoding [V(enc)] of 20 cm/s, FOV = 160, 3 mm slice thickness, image matrix size = 256x256, TR = 53 ms, TE = 11 ms, NSA = 2, flip angle = 15 degrees and 23 frames per cardiac cycle with peripheral retrospective pulse gating). Our method was developed using MATLAB R7. Errors introduced by background offset and possible aliased pixels were automatically detected and corrected if necessary in order to calculate the flow parameters that characterize CSF dynamics. The semiautomatic seed method reproducibility was evaluated and compared with the radius method by two observers analysing 21 healthy subjects. RESULTS: The measurements using the semiautomatic seed method reduced the interobservers variability (intra-class correlation [ICC] = 1.0 for stroke volume and for volumetric flow rate) versus the radius method (ICC = 0.46 for stroke volume and 0.65 for flow rate). Normal stroke volume (39.19 +/- 20.13 microl/cycle), flow rate (3.81 +/- 2.81 ml/min), maximal mean systolic velocity (5.27 +/- 1.3 cm/s) and maximal mean diastolic velocity (4.20 +/- 1.4 cm/s) were calculated with the half moon and aliasing corrected seed method. CONCLUSIONS: Semiautomatic measurements (seed method with half moon background and aliasing correction) allow a generalization of the calculus of flow parameters with great consistency and independency of the operator.
Abstract: OBJECTIVE: To characterise the evolution of myocardial perfusion during the first 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging (CMR) and determine its significance. DESIGN: Prospective cohort design. SETTING: Single-centre study in a teaching hospital in Spain. PATIENTS: 40 patients with a first ST-elevation myocardial infarction, single-vessel disease and thrombolysis in myocardial infarction (TIMI) grade 3 flow (stent in 33 patients) underwent rest and low-dose dobutamine CMR 7 (SD 1) and 184 (SD 11) days after infarction. Microvascular perfusion was assessed at rest by visual assessment and quantitative analysis of first-pass perfusion CMR. Of the 640 segments, 290 segments subtended by the infarct-related artery (IRA) were focused on. RESULTS: Both 1 week and 6 months after infarction, segments with normal perfusion showed more wall thickening, contractile reserve and wall thickness, and less transmural necrosis, p <0.05 in all cases. Of 76 hypoperfused segments at the first week, 47 (62%) normalised perfusion at the sixth month. However, 42 segments (14% of the whole group) showed chronic abnormal perfusion; these segments showed worse CMR indices in the late phase (p<0.05 in all cases). CONCLUSIONS: In patients with an open IRA, more than half of the segments with abnormal perfusion at the first week are normally perfused after six months. First-pass perfusion CMR shows that in a small percentage of segments, abnormal perfusion may become a chronic phenomenon-these areas have a more severe deterioration of systolic function, wall thickness, contractile reserve and the transmural extent of necrosis.
Abstract: AIMS: We aimed to characterize the extension of Q-waves after a first ST-segment elevation myocardial infarction using body surface map (BSM) and its relationship with infarct size quantified with cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: Thirty-five patients were studied 6 months after a first ST-segment elevation myocardial infarction (23 anterior, 12 inferior). All cases had single-vessel disease and an open artery. The extension of Q-waves was analyzed by means of a 64-lead BSM. Infarct size was quantified with CMR. Absence of Q-waves in BSM was observed in 5 patients (14%), 2 of whom (40%) had >1 segment with transmural necrosis. Absence of Q-waves in 12-lead ECG was observed in 8 patients (23%), 7 of whom (87%) had >1 segment with transmural necrosis. Patients with inferior infarctions (n=12, 34%) showed a larger number of Q-waves in BSM (18+/-7.1 leads) than patients with anterior infarctions (n=23, 66%; 3.7+/-3.6 leads; p<0.0001). When the study group was analysed as a whole, the total number of Q-waves detected in BSM did not correlate with the number of necrotic segments (r=0.15; p=0.4). In anterior infarctions, a number of Q-waves >median (2 leads) was related to a higher number of necrotic segments (5.1+/-2.4 vs. 2+/-2.2 segments; p=0.004). The same was observed in inferior infarctions (median 20 leads: 3.5+/-1.9 vs. 1.2+/-1.2 segments; p=0.03). CONCLUSION: In a stable phase after a first ST-segment elevation myocardial infarction, absence of Q-waves does not mean non-transmural necrosis. Using BSM, extension of Q-waves is much higher in inferior infarctions; a separate analysis depending on infarct location is necessary. A major BSM-derived extension of Q-waves is related to larger infarct size both in anterior and in inferior infarctions.
Abstract: INTRODUCTION AND OBJECTIVES: Quantification of intravascular ultrasound (IVUS) images is essential in ischemic heart disease and interventional cardiology. Manual analysis is very slow and expensive. We describe an automated computerized method of analysis that requires only minimal initial input from a specialist. METHODS: This study was carried out by interventional cardiologists and biomedical engineers working in close collaboration. We developed software in which it was necessary only to identify the media-adventitia boundary in a few images taken from the whole sequence. A three-dimensional reconstruction was then generated from each sequence, from which measurements of areas and volumes could be derived automatically. In total, 2300 randomly selected images from video sequences of 11 patients were analyzed. RESULTS: Results obtained using the proposed method differed only minimally from those obtained with the manual method: for vessel area measurements, the variability was 0.08 (0.07) (mean absolute error [standard deviation] normalized to the actual value; this corresponds to an error of 0.08 mm(2) per mm(2) of vessel area); for lumen area, 0.11 (0.11) (normalized), and for plaque volume, 0.5 (0.3) (normalized). Regions with severe lesions (<4 mm(2)) were correctly identified in more than 90% of cases. Specialist time needed for each reconstruction was 10 (8) minutes (vs 60 [10] minutes for manual analysis; P< .0001). CONCLUSIONS: The computerized method used dramatically reduced the time and effort needed for IVUS sequence analysis, and the automated measurements obtained were very promising.
Abstract: The analysis of the angiogenesis in hepatic lesions is an important marker of tumour aggressiveness and response to therapy. However, the quantitative analysis of this fact requires a deep knowledge of the hepatic perfusion. The development of pharmacokinetic models constitutes a very valuable tool, but it is computationally intensive. Moreover, abdominal imaging processing increases the computational requirements since the movement of the patient makes images in a time series incomparable, requiring a previous pre-processing. This work presents a Grid environment developed to deal with the computational demand of pharmacokinetic modelling. This article proposes and implements a four-level software architecture that provides a simple interface to the user and deals transparently with the complexity of Grid environment. The four layers implemented are: Grid Layer (the closest to the Grid infrastructure), the Gate-to- Grid (which transforms the user requests to Grid operations), the Web Services layer (which provides a simple, standard and ubiquitous interface to the user) and the Application Layer. An application has been developed on top of this architecture to manage the execution of multi-parametric groups of co-registration actions on a large set of medical images. The execution has been performed on the EGEE Grid infrastructure. The application is platform-independent and can be used from any computer without special requirements.
Abstract: A new method for the assessment of the atrial fibrillatory wave (AFW) from the ECG is presented. This methodology is suitable for signals registered from Holter systems, where the reduced number of leads is insufficient to exploit the spatial information of the ECG. The temporal dependence of the bio-electrical activity were exploited using principal component analysis. The main features of ventricular and atrial activity were extracted, and several basis signals for each subspace were determined. Hence, the estimated (AFW) are reconstructed exclusively from the basis signals that formed the atrial subspace. Its main advantage with respect to adaptive template subtraction techniques was its robustness to variations in the QRST morphology, which thus minimised QRST residua. The proposed approach was first validated using a database of simulated recordings with known atrial activity content. The estimated AFW was compared with the original AFW, obtaining correlation indices of 0.774 +/- 0.106. The suitability of this methodology for real recordings was also proven, though its application to a set of paroxysmal AF ECGs. In all cases, it was possible to detect the main frequency peak, which was between 4.6 Hz and 6.9 Hz for the patients under study.
Abstract: INTRODUCTION: Since the arrival of neuroimaging numerous studies have tried to analyze the differences between emotional and non-emotional response. The majority of these studies use visual approach (faces) and begin with data in normal subjects. The present study introduces a new paradigm for the study of emotional response based on auditory approach and designed specifically for the study of psychoses. METHOD: The most frequent words heard by psychotic patients with auditory hallucinations were analyzed. They were classified according to five categories which were compared with 13 other words with the same structure but with a neutral emotional valency. This paradigm was applied to see the cerebral activation with functional magnetic resonance imaging (fMRI) in 10 right handed healthy males. RESULTS: In the preliminary analysis a clear differentiation is observed depending on the type of stimulus applied (emotional or non-emotional), both in the intensity of activation (right and left temporal cortex) as in the activation of specific areas (right precentral and supramarginal gyrus) only with the emotional stimulus. CONCLUSIONS: The present paradigm allows the observation of a differentiation in the cerebral activation to emotional auditory stimulus and could be of utility in the study of psychotic patients.
Abstract: OBJECTIVES: We analyzed the safety and feasibility of myocardial echocardiography with intracoronary injection of contrast, its effect on left ventricular remodeling and systolic function, and its relationship with angiography and magnetic resonance imaging (MRI) for the evaluation of post-infarction coronary microcirculation. PATIENTS AND METHOD: Thirty patients with a first ST-elevation myocardial infarction and a patent infarct-related artery were studied. Mean perfusion score of the infarcted area was analyzed with myocardial echocardiography. TIMI and Blush grades (angiography) were determined. Mean perfusion score (MRI-perfusion), end-diastolic volume index and ejection fraction were determined with MRI. At 6 months all studies were repeated in the first 17 patients. RESULTS: Forty-seven perfusion studies (30 in the first week and 17 after 6 months) were done without complications (6 [2] min per myocardial echocardiography study). Normal perfusion (myocardial echocardiography 0.75) was detected in 67% of the patients. Myocardial echocardiography was the best predictor of end-diastolic volume (r=-0.69; P =.002) and ejection fraction (r=0.72; P=.001) after 6 months. Normal perfusion was observed in 80% of the patients with TIMI grade 3, and in 14% of those with TIMI grade 2. Of the 40 studies in patients with TIMI grade 3, normal perfusion was seen in 85% of the patients with Blush grade 2-3 and in 50% of those with Blush 0-1. Perfusion was also normal in 90% of the patients with MRI-perfusion =1 and in 62% of those with MRI-perfusion < 1. CONCLUSIONS: Myocardial echocardiography is a feasible and relatively rapid technique with no side effects. This technique provided the most reliable perfusion index for predicting late left ventricular remodeling and systolic function. To achieve normal perfusion, TIMI grade 3 is necessary but does not guarantee success. In patients with TIMI grade 3, a normal Blush score or a normal MRI-perfusion study suggests good reperfusion.
Abstract: A novel technique called "Noquist" is introduced for the acceleration of dynamic cardiac magnetic resonance imaging (CMRI). With the use of this technique, a more sparsely sampled dynamic image sequence is reconstructed correctly, without Nyquist foldover artifact. Unlike most other reduced field-of-view (rFOV) methods, Noquist does not rely on data substitution or temporal interpolation to reconstruct the dynamic image sequence. The proposed method reduces acquisition time in dynamic MRI scans by eliminating the data redundancy associated with static regions in the dynamic scene. A reduction of imaging time is achieved by a fraction asymptotically equal to the static fraction of the FOV, by omitting acquisition of an appropriate subset of phase-encoding views from a conventional equidistant Cartesian acquisition grid. The theory behind this method is presented along with sample reconstructions from real and simulated data. Noquist is compared with conventional cine imaging by retrospective selection of a reduced data set from a full-grid conventional image sequence. In addition, a comparison is presented, using real and simulated data, of our technique with an existing rFOV technique that uses temporal interpolation. The experimental results confirm the theory, and demonstrate that Noquist reduces scan time for cine MRI while fully preserving both spatial and temporal resolution, but at the cost of a reduced signal-to-noise ratio (SNR).
