Said R. Rabbani

Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS)

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM−1s−1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

Multigrid priors for a Bayesian approach to fMRI

We introduce multigrid priors to construct a Bayesian-inspired method to asses brain activity in functional magnetic resonance imaging (fMRI). A sequence of different scale grids is constructed over the image. Starting from the finest scale, coarse grain data variables are sequentially defined for each scale. Then we move back to finer scales, determining for each coarse scale a set of posterior probabilities. The posterior on a coarse scale is used as the prior for activity at the next finer scale. To test the method, we use a linear model with a given hemodynamic response function to construct the likelihood. We apply the method both to real and simulated data of a boxcar experiment. To measure the number of errors, we impose a decision to determine activity by setting a threshold on the posterior. Receiver operating characteristic (ROC) curves are used to study the dependence on threshold and on a few hyperparameters in the relation between specificity and sensitivity. We also study the deterioration of the results for real data, under information loss. This is done by decreasing the number of images in each period and also by decreasing the signal to noise ratio and compare the robustness to other methods.

Structural and Ultrastructural Analysis of the Cervical Discs of Young and Elderly Humans

Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a “pathologic” collagen type and changes are generally similar throughout the disc. Understanding the collagen and ultrastructural substrate of degenerative changes in the human disc is an essential step in planning restorative therapies.

A Novel Approach to Intraoral Mandibular Nerve Anesthesia: Changing Reference Planes in the Gow-Gates Block Technique

PURPOSE The Gow-Gates technique is said to have several advantages over traditional techniques to achieve mandibular nerve anesthesia; however, its routine use is quite limited, mainly due to complications during visual alignment of reference landmarks. The purpose of this study was to verify the validity and accuracy of a new method to reach the injection site. MATERIAL AND METHODS Fifteen magnetic resonance images were captured. Distances from the ideal injection point in the condylar neck (puncture ideal) to the injection points located in the alpha and beta plane intersection (puncture Gow-Gates and puncture modified) were measured and compared. RESULTS Positive and significant (P <or= .003) Pearson correlations between landmarks and injection points confirmed the validity of the modified technique. Paired t test showed that the segment line puncture ideal-puncture modified, 5.17 mm, was 3 times shorter (P < .001) than the segment line puncture ideal-puncture Gow-Gates, 17.91 mm. As calculated by linear regression, establishing the injection point of the modified technique depended only on the anteroposterior and lateromedial condyle positions. CONCLUSIONS The modified technique proved to be valid and precise and has a determined and an effective injection site.

Analysis of nuclear relaxation in granular systems

The longitudinal nuclear magnetic relaxation time, T1, of powdered samples was analyzed following the theory proposed by Browstein and Tarr to explain the T1 reduction of water confined in biological cells and the proposed by Rabbani and Edmonds where the molecular diffusion in liquids is substituted by spin diffusion to interpret the T1 behavior in solid particles. We have shown that the multiexponential character of magnetization decay in solid particles with a narrow band size distribution allows to evaluate the spin diffusion coefficient of this material. On the other hand if the diffusion coefficient of a material is given and the average size of a sample of this material is known the relaxation decay curve can be used to determine the surface relaxivity as well as the relative size of particles present in the other samples of same material. However, this analysis is unable to provide the absolut measurement of the grain sizes. Furthermore, it is shown that the grain geometry does not influence the relaxation decay curve.

Approximate solution for kinetic differential equations

SummaryIn the present work we show the analysis of an approximate solution for the coupled kinetic differential equations of a defect involving processes of untrapping, retrapping and recombination annihilation, using the Poincaré-Dulac theorem.

BOLD response analysis by iterated local multigrid priors

We present a non parametric Bayesian multiscale method to characterize the Hemodynamic Response HR as function of time. This is done by extending and adapting the Multigrid Priors (MGP) method proposed in (S.D.R. Amaral, S.R. Rabbani, N. Caticha, Multigrid prior for a Bayesian approach to fMRI, NeuroImage 23 (2004) 654-662; N. Caticha, S.D.R. Amaral, S.R. Rabbani, Multigrid Priors for fMRI time series analysis, AIP Conf. Proc. 735 (2004) 27-34). We choose an initial HR model and apply the MGP method to assign a posterior probability of activity for every pixel. This can be used to construct the map of activity. But it can also be used to construct the posterior averaged time series activity for different regions. This permits defining a new model which is only data-dependent. Now in turn it can be used as the model behind a new application of the MGP method to obtain another posterior probability of activity. The method converges in just a few iterations and is quite independent of the original HR model, as long as it contains some information of the activity/rest state of the patient. We apply this method of HR inference both to simulated and real data of blocks and event-related experiments. Receiver operating characteristic (ROC) curves are used to measure the number of errors with respect to a few hyperparameters. We also study the deterioration of the results for real data, under information loss. This is done by decreasing the signal to noise ratio and also by decreasing the number of images available for analysis and compare the robustness to other methods.

Multigrid Priors for fMRI time series analysis

We deal with the problem of constructing priors for data analysis in order to asses brain activity in functional Magnetic Resonance Imaging (fMRI). Our method is an example of how a prior distribution can incorporate what could be termed as conventional prior information as well as other information such as that steming from knowledge of what constitues a reasonable likelihood.Brain activity during a cognitive, sensorial or motor task presents a certain level of localization and spatial correlations with different scales involved in the problem. These suggests a multiscale iterative procedure to construct the prior. Grids of different scales are constructed over the image. Spatially coarse grain data variables are defined for each scale, until a single voxel time series is obtained. The process consists in iterating back to finer scales, determining for each coarse scale a set of posterior probabilities. The posterior on a coarse scale is used as the prior for activity at the next finer scale. We have app...

Imagem por ressonância magnética na investigação da cabeça de cães

Magnetic resonance imaging (MRI) is the most sensitive method of diagnostic imaging to evaluate soft tissues, specially the brain, however it is expensive. The method is based on the nuclear magnetic resonance phenomenon that occurs when atomic nucleus with magnetic proprieties in the body are submitted to a strong magnetic field, and excited with radio frequency generating a radio frequency signal captured by a receptive antenna. The signal is processed by Fourier Transform for the image formation. This study had the objective to obtain 10 complete exams of heads in cadavers of normal dogs to MRI and to make an Atlas of head structures. The images were obtained with a magnetic resonance unit Gyroscan S15/HP Philips using a magnetic field of 1,5Tesla. The cadavers were positioned with the head into a human head coil and submitted to sagittal slices used to plan transverse and dorsal slices in T1, T2 and DP spin-echo sequences. In T1 we adjusted TR=400ms and TE=30ms, in T2 TR=2000ms and TE=80ms and in DP TR=2000ms and TE=30ms. The slice thickness was 4mm, the number of averages 2, the matrix 256x256, the factor 1,0 and the field of view 14cm. The duration of the complete exam of the head was 74,5minutes. The images obtained with the described sequences and with the human head coil was of good quality. In T1 fat was hyperintense and fluid was hypointense. In T2 fat was less hyperintense and fluid was hyperintense. The cortical bone and the air were hypointense in all sequences used because of the low proton density. The DP sequence showed the best contrast between white and gray matter when compared with T2 and T1 sequences. Distinction of cerebral sulcus and gyrus was possible because T2 showed the cerebrospinal fluid. The identification of bone structures that compound the region, muscles, main venous and arterial vessels and structures of the central nervous system, besides elements of the digestory and respiratory systems and structures of the eyes among others was possible through contrast obtained with MRI. In this study the MRI acquired in T1, DP and T2 were complementary for the anatomic study of the head and been able to demonstrate the structures of the canine head with rich anatomic details. The time used to do the complete exam of the head is compatible with the use in live animals since properly anesthetized and controlled. We had opened a way for the study of live animals and for the beginning of disease investigation, mainly that of neurologic origin because this technique is excellent for brain visualization.