Biomedical subjects

Yaniv Assaf

Publications and source records attributed to Yaniv Assaf.

17 recordsLinked to original sources

PubMed2007

Virtual definition of neuronal tissue by cluster analysis of multi-parametric imaging (virtual-dot-com imaging).

Individual mapping of cerebral, morphological, functionally related structures using MRI was carried out using a new multi-contrast acquisition and analysis framework, called virtual-dot-com imaging. So far, conventional anatomical MRI has been able to provide gross segmentation of gray/white matter boundaries and a few sub-cortical structures. By combining a handful of imaging contrasts mechanisms (T1, T2, magnetization transfer, T2* and proton density), we were able to further segment sub-cortical tissue to its sub-nuclei arrangement, a segmentation that is difficult based on conventional, single-contrast MRI. Using an automatic four-step image and signal processing algorithm, we segmented the thalamus to at least 7 sub-nuclei with high similarity across subjects and high statistical significance within subjects (p<0.0001). The identified sub-nuclei resembled the known anatomical arrangement of the thalamus given in various atlases. Each cluster was characterized by a unique MRI contrast fingerprint. With this procedure, the weighted proportions of the different cellular compartments could be estimated, a property available to date only by histological analysis. Each sub-nucleus could be characterized in terms of normalized MRI contrast and compared to other sub-nuclei. The different weights of the contrasts (T1/T2/T2*/PD/MT, etc.) for each sub-nuclei cluster might indicate the intra-cluster morphological arrangement of the tissue that it represents. The implications of this methodology are far-ranging, from non-invasive, in vivo, individual mapping of histologically distinct brain areas to automatic identification of pathological processes.

Adult↗

PubMed2006

Regional axonal abnormalities in first episode schizophrenia: preliminary evidence based on high b-value diffusion-weighted imaging.

Connectivity has been implicated as a major source of brain abnormality in schizophrenia. The current study focused on first episode schizophrenia to identify possible early pathology in axonal structure. First episode schizophrenic patients and healthy controls were scanned in a 1.5-Tesla scanner during which high b-value diffusion-weighted imaging (DWI) was acquired. Histogram analysis revealed a decrease in overall white matter (WM) tissue, indicating relative axonal abnormality in the schizophrenic group. Subsequent analysis found that this effect was contributed mainly by anterior-prefrontal bundles. Moreover, negative correlations were found between positive and negative symptom severity and whole head WM displacement peak value, implying an overall lesser degree of WM integrity is associated with greater symptom severity. These preliminary results suggest that WM abnormality, as measured by high b-value DWI, is already a significant pathological brain marker in early stage of schizophrenia.

Adult↗

PubMed2006

Sleep-anticipating effects of melatonin in the human brain.

Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous regulator of the sleep-wake cycle. The effects of melatonin on brain activities and their relation to induction of sleepiness were studied in a randomized, double-blind, placebo controlled functional magnetic resonance imaging (fMRI) study. Melatonin, but not placebo, reduced task-related activity in the rostro-medial aspect of the occipital cortex during a visual-search task and in the auditory cortex during a music task. These effects correlated with subjective measurements of fatigue. In addition, melatonin enhanced the activation in the left parahippocampus in an autobiographic memory task. Results demonstrate that melatonin modulates brain activity in a manner resembling actual sleep although subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin on brain activity is essentially different from that of sleep deprivation thus revealing differences between fatigues related to the circadian sleep regulation as opposed to increased homeostatic sleep need. Our findings highlight the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep.

Adult↗

PubMed2006

Characterization of displaced white matter by brain tumors using combined DTI and fMRI.

In vivo white matter tractography by diffusion tensor imaging (DTI) has become a popular tool for investigation of white matter architecture in the normal brain. Despite some unresolved issues regarding the accuracy of DTI, recent studies applied DTI for delineating white matter organization in the vicinity of brain lesions and especially brain tumors. Apart from the intrinsic limitations of DTI, the tracking of fibers in the vicinity or within lesions is further complicated due to changes in diseased tissue such as elevated water content (edema), tissue compression and degeneration. These changes deform the architecture of the white matter and in some cases prevent definite selection of the seed region of interest (ROI) from which fiber tracking begins. We show here that for displaced fiber systems, the use of anatomical approach for seed ROI selection yields insufficient results. Alternatively, we propose to select the seed points based on functional MRI activations which constrain the subjective seed ROI selection. The results are demonstrated on two major fiber systems: the pyramidal tract and the superior longitudinal fasciculus that connect critical motor and language areas, respectively. The fMRI based seed ROI selection approach enabled a more comprehensive mapping of these fiber systems. Furthermore, this procedure enabled the characterization of displaced white matter using the eigenvalue decomposition of DTI. We show that along the compressed fiber system, the diffusivity parallel to the fiber increases, while that perpendicular to the fibers decreases, leading to an overall increase in the fractional anisotropy index reflecting the compression of the fiber bundle. We conclude that definition of the functional network of a subject with deformed white matter should be done carefully. With fMRI, one can more accurately define the seed ROI for DTI based tractography and to provide a more comprehensive, functionally related, white matter mapping, a very important tool used in pre-surgical mapping.

Anisotropy↗

PubMed2005

Susceptibility-matched envelope for the correction of EPI artifacts.

Fast gradient echo sequences, such as echo planer imaging (EPI) and spiral imaging, are vulnerable to artifacts resulting from B(0) inhomogeneities. A major contribution to these artifacts is the susceptibility variation across the head, which is most severe in regions adjacent to air-tissue interfaces, such as the mouth, nasal sinuses, ears and the cortex. Susceptibility artifacts can cause geometrical distortions in the image as well as loss of signal due to T(2)* dephasing. The extent of these artifacts increases with the main field, thus compromising the signal-to-noise ratio (SNR) benefit gained in higher fields. In the current work, inhomogeneity caused by susceptibility variations at the external boundary of the human body has been corrected by surrounding the organs with a liquid without hydrogen atoms and whose susceptibility is similar to that of the imaged organ. EPI experiments were conducted on head-sized phantom, human brain, hand and legs. This method causes minimal patient inconvenience and no interference with any function of the scanner, thus yielding a simple and efficient solution for the correction of B(0) variation.

Artifacts↗

PubMed2005

Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain.

High b value diffusion-weighted images sampled at high angular resolution were analyzed using a composite hindered and restricted model of diffusion (CHARMED). Measurements and simulations of diffusion in white matter using CHARMED provide an unbiased estimate of fiber orientation with consistently smaller angular uncertainty than when calculated using a DTI model or with a dual tensor model for any given signal-to-noise level. Images based on the population fraction of the restricted compartment provide a new contrast mechanism that enhances white matter like DTI. Nevertheless, it is assumed that these images might be more sensitive than DTI to white matter disorders. We also provide here an experimental design and analysis framework to implement CHARMED MRI that is feasible on human clinical scanners.

Algorithms↗

PubMed2005

Normal white matter development from infancy to adulthood: comparing diffusion tensor and high b value diffusion weighted MR images.

PURPOSE: To evaluate the sensitivity of high b value diffusion weight magnetic resonance imaging (DWI) in detecting normal white matter maturation, compare it to conventional diffusion tensor imaging (DTI), and to obtain normative quantitative data using this method. MATERIALS AND METHODS: High b value DWI (b(max) = 6000 sec/mm(2)) using q-space analysis and conventional DTI (b = 1000 sec/mm(2)) were performed on 36 healthy subjects aged 4 months to 23 years. Fractional-anisotropy (FA), apparent-displacement, and apparent-probability values were measured in all slices and in six regions of interest (ROIs) of large fiber tracks. Values were correlated with each other and with age using regression analysis. RESULTS: FA, displacement, and probability indices from all slices were highly correlated with each other (r > 0.87, P < 0.0001) and with age (r > 0.82, P < 0.0001). All age-related changes in the six pre-determined ROIs were best fitted by mono-exponential functions. Changes in the splenium extended to a later age when compared with the genu of the corpus-callosum, while the centrum semi-ovale demonstrated the latest changes with age. CONCLUSIONS: High b-value DWI and DTI showed changes in white matter from infancy through adulthood. However, high b-value detects a signal that is likely to originate mainly from the intra-axonal water population, and thus may represent different aspects of development and different sensitivity to pathology.

Adolescent↗

PubMed2005

Improved detectability of experimental allergic encephalomyelitis in excised swine spinal cords by high b-value q-space DWI.

Experimental allergic encephalomyelitis (EAE) is the primary experimental model of multiple sclerosis (MS), which involves both inflammation and demyelination and is known to be species-dependent. Spinal cord abnormalities were found in more than 80% of postmortem specimens of MS patients. In the present study, T1, T2 and high b-value q-space diffusion-weighted magnetic resonance imaging (MRI) were used, for the first time, to characterize the EAE model in excised swine spinal cords. The MR images were compared with histological staining and clinical scoring. Although all spinal cords were excised from swine with severe or very severe (clinical score between 3 to 5 on a scale of 5) motor impairments, T1- and T2-weighted MRI revealed white matter (WM) abnormalities in only five of the ten EAE diseased spinal cords studied, while high b-value q-space diffusion weighted MRI (q-space DWI) detected WM abnormalities in all diseased spinal cords studied. Interestingly, high b-value q-space DWI was able to detect abnormalities in the normal appearing white matter (NAWM) even in spinal cords where no plaques were identified by the T1- and T2-weighted MR images. Good anatomical correlation was observed between the high b-value q-space MR images and histology. The extent of DWI abnormalities paralleled the clinical scoring and correlated with histology. In addition, areas classified as NAWM by the T1- and T2-weighted MR images that showed abnormalities in the q-space DWI were also found to have abnormal histology. This improved detection level of the EAE model by high b-value q-space DWI over conventional T1-, and T2-weighted MRI is briefly discussed.

Animals↗

PubMed2005

White matter changes in multiple sclerosis: correlation of q-space diffusion MRI and 1H MRS.

OBJECTIVE: To explore the diagnostic usefulness of high b-value diffusion magnetic resonance brain imaging ("q-space" imaging) in multiple sclerosis (MS). More specifically, we aimed at evaluating the ability of this methodology to identify tissue damage in the so-called normal-appearing white matter (NAWM). DESIGN: In this study we examined the correlation between q-space diffusion imaging and magnetic resonance spectroscopy (MRS)-based two-dimensional 1H chemical shift imaging. Eight MS patients with different degree of disease severity and seven healthy subjects were scanned in a 1.5-T magnetic resonance imaging (MRI) scanner. The MRI protocol included diffusion tensor imaging (DTI) (with bmax of 1000 s/mm2), high b-value diffusion-weighted imaging (with bmax of 14,000 s/mm2) and 2D chemical shift imaging. The high b-value data set was analyzed using the q-space methodology to produce apparent displacement and probability maps. RESULTS: We found that the q-space diffusion displacement and probability image intensities correlated well with N-acetylaspartate levels (r=.61 and .54, respectively). Furthermore, NAWM that was abnormal on MRS was also found to be abnormal using q-space diffusion imaging. In these areas, the q-space displacement values increased from 3.8+/-0.2 to 4.6+/-0.6 microm (P<.02), the q-space probability values decreased from 7.4+/-0.3 to 6.8+/-0.3 (P<.002), while DTI revealed only a small, but still significant, reduction in fractional anisotropy values from 0.40+/-0.02 to 0.37+/-0.02 (P<.05). CONCLUSION: High b-value diffusion imaging can detect tissue damage in the NAWM of MS patients. Despite the theoretical limitation of this method, in practice it provides additional information which is clinically relevant for detection of tissue damage not seen in conventional imaging techniques.

Adult↗

PubMed2005

Chronic cholinergic imbalances promote brain diffusion and transport abnormalities.

Cholinergic imbalances occur after traumatic effects and in the initial stages of neurodegenerative diseases, but their long-lasting effects remained largely unexplained. To address this, we used TgS transgenic mice constitutively overexpressing synaptic acetylcholinesterase (AChE-S) and presenting a complex phenotype of progressive neurodeterioration. T1- and T2-weighted magnetic resonance (MR) brain images appeared similar. However, diffusion-weighted MRI showed decreased baseline water apparent diffusion coefficient in the brains of TgS animals. Furthermore, contrast-enhanced MRI after gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) injection demonstrated slower recovery of normal signals in the TgS brains than with controls. Perfusion MR imaging and difference T1 maps calculated from pre- postcontrast T1-weighted MR images indicated accumulation of more Gd-DTPA molecules in the TgS brains than in the parent strain, reflecting impaired blood-brain barrier (BBB) functioning in these transgenic mice. To explore the molecular mechanism(s) underlying these global phenotypes, we performed microarray analysis in the stress-controlling prefrontal cortex of TgS vs. strain-matched wild-type animals. Profound overexpression of numerous ion channels, transporters, and adhesion genes was confirmed by real time RT-PCR tests. Immunohistochemical and immunoblot analyses revealed corresponding increases in the level and cellular distributions of the chloride channel CLCN3 and the water channel AQP4, both of which contribute to BBB maintenance. Our study attributes to balanced cholinergic neurotransmission, a central role in the brain's maintenance of water diffusion and ion transport, and indicates that chronic impairments in this maintenance facilitate neurodeterioration through interference with BBB function.

Acetylcholine↗

PubMed2004

New modeling and experimental framework to characterize hindered and restricted water diffusion in brain white matter.

To characterize anisotropic water diffusion in brain white matter, a theoretical framework is proposed that combines hindered and restricted models of water diffusion (CHARMED) and an experimental methodology that embodies features of diffusion tensor and q-space MRI. This model contains a hindered extra-axonal compartment, whose diffusion properties are characterized by an effective diffusion tensor, and an intra-axonal compartment, whose diffusion properties are characterized by a restricted model of diffusion within cylinders. The hindered model primarily explains the Gaussian signal attenuation observed at low b values; the restricted non-Gaussian model does so at high b. Both high and low b data obtained along different directions are required to estimate various microstructural parameters of the composite model, such as the nerve fiber orientation(s), the T2-weighted extra- and intra-axonal volume fractions, and principal diffusivities. The proposed model provides a description of restricted diffusion in 3D given by a 3D probability distribution (average propagator), which is obtained by 3D Fourier transformation of the estimated signal attenuation profile. The new model is tested using synthetic phantoms and validated on excised spinal cord tissue. This framework shows promise in determining the orientations of two or more fiber compartments more precisely and accurately than with diffusion tensor imaging.

Animals↗

PubMed2004

The effect of rotational angle and experimental parameters on the diffraction patterns and micro-structural information obtained from q-space diffusion NMR: implication for diffusion in white matter fibers.

Diffusion NMR may provide, under certain experimental conditions, micro-structural information about confined compartments totally non-invasively. The influence of the rotational angle, the pulse gradient length and the diffusion time on the diffusion diffraction patterns and q-space displacement distribution profiles was evaluated for ensembles of long cylinders having a diameter of 9 and 20 microm. It was found that the diffraction patterns are sensitive to the rotational angle (alpha) and are observed only when diffusion is measured nearly perpendicular to the long axis of the cylinders i.e., when alpha= 90 degrees +/- 5 degrees under our experimental conditions. More importantly, we also found that the structural information extracted from the displacement distribution profiles and from the diffraction patterns are very similar and in good agreement with the experimental values for cylinders of 20 microm or even 9 microm, when data is acquired with parameters that satisfy the short gradient pulse (SGP) approximation (i.e., delta -->0) and the long diffusion time limit. Since these experimental conditions are hardly met in in vitro diffusion MRI of excised organs, and cannot be met in clinical MRI scanners, we evaluated the effect of the pulse gradient duration and the diffusion time on the structural information extracted from q-space diffusion MR experiments. Indeed it was found that, as expected, accurate structural information, and diffraction patterns are observed when Delta is large enough so that the spins reach the cylinders' boundaries. In addition, it was found that large delta results in extraction of a compartment size, which is smaller than the real one. The relevance of these results to q-space MRI of neuronal tissues and fiber tracking is discussed.

Diffusion Magnetic Resonance Imaging↗

PubMed2004

Structural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord.

Diffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d(12)) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d(12) are 7.21 +/- 0.11 and 1.16 +/- 0.05 microm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 +/- 0.13 and 1.01 +/- 0.05 microm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues.

Animals↗

PubMed2003

Hypertension and neuronal degeneration in excised rat spinal cord studied by high-b value q-space diffusion magnetic resonance imaging.

Hypertension is one of the major risk factors of stroke and vascular dementia (VaD). We used stroke prone spontaneous hypertensive rats (SPSHRs) as a model for neuronal degeneration frequently occurring in humans with vascular disease. Recently, high b value q-space diffusion-weighted imaging (DWI) was shown to be very sensitive to the pathophysiological state of the white matter. We studied the spinal cords of SPSHR rats ex vivo after the appearance of motor impairments using diffusion anisotropy and q-space diffusion imaging (measured at a high b value of up to 1 x 10(5) s/mm(2)). The diffusion anisotropy images computed from low b value data set (b(max) approximately 2500 s/mm(2)) showed a small but statistically significant decrease (approximately 12%, P < 0.05) in the diffusion anisotropy in the spinal cords of the SPSHR group as compared to control rats. However, more significant changes were found in the high b value q-space diffusion images. The q-space displacement values in the white matter of the SPSHR group were found to be higher by more than 70% (P < 0.002) than that of the control group. These observations concurred with electron microscopy (EM) that showed significant demyelination in the spinal cords of the SPSHR group. These results seem to indicate that high b value q-space DWI might be a sensitive method for following demyelination and axonal loss associated with vascular insults.

Animals↗

PubMed2003

Delineating gray and white matter involvement in brain lesions: three-dimensional alignment of functional magnetic resonance and diffusion-tensor imaging.

OBJECT: The role of functional magnetic resonance (fMR) imaging has become increasingly important in the presurgical mapping of gray matter. Neurosurgical interventions often involve fiber bundles that connect critical functional areas. Recently, diffusion-tensor (DT) imaging has enabled the visualization of fiber bundle direction and integrity, thus providing the ability to delineate clearly white matter from gray matter tissue. The main objective of this study was to improve the presurgical assessment of critical functionality in the vicinity of brain lesions by combining DT and fMR imaging methodologies. METHODS: Twenty patients with various space-occupying brain lesions underwent imaging for presurgical evaluation of motor and/or somatosensory functions. The authors focus on five patients with diverse space-occupying brain lesions. Diffusion tensor-based fiber tracking and fMR imaging activation maps were superimposed in three dimensions to visualize pyramidal tracts corresponding to motor and somatosensory regional activation. CONCLUSIONS: The combination of DT and fMR imaging for presurgical functional brain mapping provides valuable information that cannot be extracted using either method alone. The validity and sensitivity of noninvasive functional mapping for surgical guidance could be improved by considering results obtained with both methods. Furthermore, the use of three-dimensional visualization seems crucial and unique for viewing and understanding the complicated spatial relationship among the lesion, gray matter activation, and white matter fiber bundles.

Adolescent↗

PubMed2002

Changes in axonal morphology in experimental autoimmune neuritis as studied by high b-value q-space (1)H and (2)H DQF diffusion magnetic resonance spectroscopy.

Experimental autoimmune neuritis (EAN) has been studied in rat sciatic nerves by a combination of high b-value (1)H and (2)H double quantum filtered (DQF) diffusion MRS. The signal decays of water in the (1)H and (2)H DQF diffusion MRS were found to be not monoexponential and were analyzed using the q-space approach. The q-space analysis of the (1)H diffusion data detected two diffusing components, one having broad and the other having narrow displacement profiles. These components were shown to be very sensitive to the progression of EAN disease. The q-space parameters were found to be abnormal at day 9 postimmunization before the appearance of clinical signs. The assignment of the component with the narrow displacement profile to axonal water has been corroborated by the (2)H DQF diffusion MRS results. The displacement and the relative population of this slow and restricted diffusing component followed the processes of demyelination, axonal loss, and remyelination that occur in EAN. The displacements extracted from the slow-diffusing component with the narrow displacement correlated well with the average size of the axons as deduced from electron microscopy (EM). The component with the broad displacement showed significant changes which were attributed to the formation of endoneurial edema. This observation was also corroborated by the (2)H DQF diffusion MRS experiments. It seems, therefore, that q-space analysis of high b-values diffusion MRS is a promising new approach for early detection and better characterization of the different pathologies associated with EAN. This study demonstrates the utility of high-b-value q-space diffusion MRS for studying white matter-associated disorders in general.

Animals↗

PubMedDate not supplied

High b-value q-space analyzed diffusion-weighted MRS and MRI in neuronal tissues - a technical review.

This review deals with high b-value q-space diffusion-weighted MRI (DW-MRI) of neuronal tissues. It is well documented that at sufficiently high b-values (and high q-values) neuronal water signal decay in diffusion experiments is not mono-exponential. This implies the existence of more than one apparent diffusing component or evidence for restriction. The assignment of the different apparent diffusing components to real physical entities is not straightforward. However, the apparent slow diffusing component that was found to be restricted to a compartment of a few microns, if originating mainly from a specific pool and if assigned correctly, may potentially be used to obtain more specific MR images with regard to specific pathologies of the CNS. This review examines the utility of analyzing high b-value diffusion MRS and MRI data using the q-space approach introduced by Callaghan and by Cory and Garroway. This approach provides displacement probability maps that emphasize, at long diffusion times, the characteristics of the apparent slow diffusing component. Examples from excised spinal cord, where the experimental conditions for which the q-space analysis of MR diffusion data was developed can be met or approached will be presented. Then examples from human MS patients, where q-space requirement for the short gradient pulse is clearly violated, are presented. In the excised spinal cord studies, this approach was used to study spinal cord maturation and trauma, and was found to be more sensitive than other conventional methods in following spinal cord degeneration in an experimental model of vascular dementia (VaD). High b-value q-space DWI was also recently used to study healthy and MS diseased human brains. This approach was found to be very sensitive to the disease load in MS, compared with other conventional MRI methods, especially in the normal appearing white matter (NAWM) of MS brains. Finally, the potential diagnostic capacity embedded in high b-value q-space analyzed diffusion MR images is discussed. The potentials and caveats of this approach are outlined and experimental data are presented that show the effect of violating the short gradient pulse (SGP) approximation on the extracted parameters from the q-space analysis.

Algorithms↗