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Eric D Schwartz

Publications and source records attributed to Eric D Schwartz.

14 recordsLinked to original sources

In vivo DTI evaluation of white matter tracts in rat spinal cord.

PURPOSE: To determine whether differences in specific spinal cord white matter (WM) tracts can be detected with in vivo DTI. MATERIALS AND METHODS: In vivo DTI was performed on six rats at the lower thoracic region using a 4.7T magnet. Axial diffusion images were obtained with diffusion gradients applied in six independent directions, with low and high b-values equal to 0 and 692 seconds/mm(2), respectively. Regions of interest (ROIs) were selected corresponding to the major spinal cord tracts, including the dorsal cortical spinal tract (dCST), fasciculus gracilis (FG), rubrospinal tract (RST), vestibulospinal tract (VST), and reticulospinal tract (ReST). RESULTS: ANOVA demonstrated overall differences between tracts for all of the DTI parameters, including fractional anisotropy (FA), trace diffusion (Tr), longitudinal diffusivity (EL = lambda(1)), and transverse diffusivity (ET = (lambda(2) + lambda(3))/2). Similarly to previous ex vivo analyses, the spinal cord tract with the largest and most widely spaced axons (VST) had the largest EL and ET. CONCLUSION: The principal diffusivities appear to reflect axon morphologic differences between the WM tracts that are not as well appreciated with FA and Tr.

Animals↗

MRI diffusion coefficients in spinal cord correlate with axon morphometry.

Following spinal cord injury, diffusion MRI (DWI) has been shown to detect injury and functionally significant neuroprotection following treatment that otherwise would go undetected with conventional MRI. The underlying histologic correlates to directional apparent diffusion coefficients (ADC) obtained with DWI have not been determined, however, and we address this issue by directly correlating ADC values with corresponding axon morphometry in the normal rat cervical spinal cord. ADC values transverse (perpendicular) and longitudinal (parallel) to axons both correlate with axon counts, however each directional ADC reflects distinct histologic parameters. DWI may therefore be capable of providing specific histologic data regarding the integrity of white matter.

Animals↗

Spinal cord diffusion tensor imaging and fiber tracking can identify white matter tract disruption and glial scar orientation following lateral funiculotomy.

Diffusion tensor magnetic resonance imaging (DTI) provides data concerning water diffusion in the spinal cord, from which white matter tracts may be inferred, and connectivity between spinal cord segments may be determined. We evaluated this potential application by imaging spinal cords from normal adult rats and rats that received cervical lateral funiculotomies, disrupting the rubrospinal tract (RST). Vitrogen and fibroblasts were transplanted into the surgical lesion at time of injury in order to fill the cavity. At 10 weeks, animals were sacrificed; the spinal cords were dissected out and then imaged in a 9.4-Tesla magnet. DTI tractography demonstrated the disruption of the rubrospinal tract axons while indicating which axon tracts were preserved. Additionally, DTI imaging could identify the orientation of glial processes in the gray matter adjacent to the site of injury. In the injured animals, reactive astrocytes in adjacent gray matter appeared to orient themselves perpendicular to white matter tracts. In summary, DTI identified not only white matter disruption following injury, but could distinguish the orientation of the accompanying glial scar.

Animals↗

Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats.

BACKGROUND AND PURPOSE: Abnormal apparent diffusion coefficient (ADC) values in injured spinal cord white matter and fibroblast transplants have been shown to correspond with qualitative histologic findings of axonal loss or regeneration. We proposed that ADC values would correlate with quantitative axonal tracing in the transected rubrospinal tract (RST). METHODS: Eleven rats received right-sided lateral funiculus lesions at C3-4 (disrupting the RST) and transplantation of fibroblasts that were unmodified or modified to secrete brain-derived neurotrophic factor (BDNF). Behavioral tests measured hindlimb function at 1, 2, 4, 6, 8, 10, and 12 weeks after injury. At 12 weeks after injury, the antegrade axon tracer biotinylated dextran amine was stereotactically injected into the red nucleus to label the injured RST axons. Animals were sacrificed 2 weeks later. Diffusion-weighted MR imaging of the excised, fixed spinal cord specimens was then performed at 9.4 T. RESULTS: In white matter surrounding transplants, ADC values transverse to axons were elevated and ADC values longitudinal to axons were decreased. These ADC values were more abnormal closer to the transplant, and this correlated with decreases in numbers of labeled RST axons. ADC values in BDNF-expressing fibroblast transplants were significantly lower than those in unmodified fibroblast transplants, and these lower values correlated with decreased axonal dieback. Behaviorally, all animals showed partial recovery, but animals with BDNF-expressing fibroblast transplants had slightly improved hindlimb function compared to those with unmodified fibroblast transplants. CONCLUSION: ADC values may be able to evaluate graft function after spinal cord injury by demonstrating the degree of axonal dieback and preservation.

Animals↗

Ex vivo evaluation of ADC values within spinal cord white matter tracts.

BACKGROUND AND PURPOSE: Our purpose was to evaluate the effect of fixative on apparent diffusion coefficient (ADC) values and anisotropy within spinal cord white matter. As glutaraldehyde (GL) better preserves axonal ultrastructure as compared with paraformaldehyde (PF), we hypothesize that spinal cord white matter fixed with GL will have increased anisotropic water diffusion as compared with specimens fixed with PF. METHODS: Eleven rats were perfusion-fixed with either 4% PF or a combination of 2.5% GL and 4% PF. Diffusion-weighted imaging of the ex vivo spinal cord was performed using a 9.4T magnet with b values up to 3100 s/mm(2). In-plane resolution was 39 mum x 39 mum, and section thickness was 500 mum. RESULTS: Overall, animals fixed with a combination of GL and PF (GL-PF) showed a greater increase in longitudinal ADC (lADC) as compared to those fixed with PF only, without differences in transverse ADC (tADC). As a consequence of the increased lADC, overall anisotropic diffusion increased in those animals fixed with GL-PF, as measured with an anisotropy index (AI = tADC/lADC). Evaluation of specific tracts demonstrated that lADC for animals fixed with GL-PF were significantly elevated in the rubrospinal, vestibulospinal, and reticulospinal tracts as compared with animals fixed with PF only. CONCLUSION: Using a fixative of GL-PL results in increased anisotropy (decreased AI values) in spinal cord white matter tracts, as compared with PF fixation only, largely owing to increases in the lADC values. This finding may be due to better fixation of intra-axonal cytoskeletal proteins that results when GL is combined with PF and sheds further light on underlying sources of anisotropic water diffusion in CNS white matter.

Animals↗

Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies.

NMR q-space imaging is a method designed to obtain information from porous materials where diffusion-diffraction phenomena were observed from which pore size was derived. Recently, the technique has been applied to the study of biological structures as well. Although diffusive diffraction has so far not been observed in multicellular systems, displacement profiles have been used with some success as a means to estimate structure size. However, there have been no quantitative correlations of the retrieved structure sizes with histology. Clearly, the complexity of tissue architecture poses significant challenges to the interpretation of q-space data. In this work, simulations were first performed on a two-compartment model to demonstrate the effects of interference of the diffraction patterns arising from intra and extra-axonal compartments and finite boundary permeability on q-space data. Second, q-space echo attenuation was simulated on the basis of histologic images of various rat spinal cord fiber tracts and the information obtained from the displacement profiles were compared with structural parameters computed from the histologic images. The results show that calculated mean displacements and kurtosis parallel mean axon size and axonal density. Finally, spatially localized q-space measurements were carried out at the locations where simulations had previously been performed, resulting in displacement data that support those obtained by simulation. The data suggest the NMR q-space approach has potential for nondestructive analysis of the axonal architecture in the mammalian spinal cord.

Animals↗

Distinguishing ischemic stroke from the stroke-like lesions of MELAS using apparent diffusion coefficient mapping.

We report two patients with migraine, acute visual field defects and other neurological symptoms who were found to have high T(2) signal and FLAIR abnormalities on brain MRI in temporal and parieto-occipital regions. In these patients, the apparent diffusion coefficient (ADC) of their lesions was increased, distinguishing these lesions from those of ischemic stroke. Both were ultimately diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We conclude that conventional MRI when used with diffusion-weighted MR imaging may be invaluable in detecting mitochondrial-related CNS dysfunction.

Adult↗

Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF.

The purpose of this study was to determine whether apparent diffusion coefficients (ADCs) in ex vivo spinal cord white matter, calculated from diffusion weighted MR (DWI) images, correlate with axonal growth and behavioral recovery following subtotal hemisection and transplantation of fibroblasts genetically modified to express brain derived neurotrophic factor (BDNF). These genetically modified fibroblasts have been shown to promote axonal growth, diminish retrograde degenerative changes in axotomized Red nucleus neurons, and are associated with behavioral recovery. Since changes in ADC appear to reflect damage to axons and myelin sheaths, which conventional MR techniques do not identify, partial repair mediated by BDNF-secreting fibroblasts should be detected with ADC measures. Accordingly, we transplanted unmodified fibroblasts (Fb-UM) or fibroblasts modified to secrete BDNF (Fb-BDNF) into cervical subtotal hemisection cavities in adult rats. Rats with Fb-BDNF transplants showed significantly greater behavioral recovery over 12 weeks, as measured by tests of forelimb exploration and open field locomotor activity. Lesion sizes and transplant survival did not differ between the two groups, but immunocytochemical examination showed substantial growth of axons into the Fb-BDNF grafts and little growth into the Fb-UM grafts. Fixed spinal cords were imaged in a 9.4-T magnet. ADCs perpendicular (tADC) and parallel (lADC) to the long axis of the cord were measured in the dorsal lateral white matter, rostral and caudal to the transplant. tADC values and anisotropy index (AI = tADC/lADC) were elevated in both transplant types, indicating white matter damage, but were closer to normal in rats with Fb-BDNF, consistent with known neuroprotection and axonal growth elicited by BDNF. Closer to normal tADC and AI values correlated with improved behavioral recovery. These findings suggest that high-resolution imaging with measurement of tADC and lADC can provide a measure of functionally significant repair that may otherwise go undetected with conventional MR techniques.

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Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment.

Diffusion-based magnetic resonance imaging (MRI) (DWI) has been shown experimentally to detect both injury and functionally significant neuroprotection of injured spinal cord white matter that would otherwise go undetected with conventional MRI techniques. The diffusion of water in the central nervous system (CNS) is thought to be affected by both its location (intracellular or extracellular), and by diffusion barriers formed by cell membranes and myelin sheaths. There is, however, controversy concerning how to obtain, interpret, and present DWI data. Computer simulations and MR microscopy have been helpful in resolving some of these issues, as well as determining exact histologic correlates to DWI findings.

Animals↗

Complete regression of intracranial arteriovenous malformations.

BACKGROUND: Spontaneous and complete regression of intracranial arteriovenous malformations (AVMs) is a rare occurrence, with only 59 angiographically proven cases reported in the English literature. We present three new cases and perform a literature review to determine possible mechanisms underlying this unusual phenomenon. METHODS: Three patients with angiographically proven AVMs demonstrated complete obliteration of the AVM on follow-up angiography. Two patients had MRIs performed at the time of follow-up angiography. RESULTS: A literature review of all reported cases shows that the vast majority (88%) of spontaneously closing AVMs had a single draining vein as did our three cases. In addition, hemodynamic alterations of intracranial (IC) blood flow, including intracranial hemorrhage, were seen in a majority (79%) of patients, including two of our three cases. MRI was performed in two of our three cases and showed a thrombosed-draining vein in both. CONCLUSIONS: Complete spontaneous regression of intracranial AVMs is a rare occurrence. The phenomenon seems to require the interaction of hemodynamic changes in compromising or closing the limited, usually single, venous drainage pathway from the AVM. Hemorrhage may contribute to the effect by further compromising flow though the lesion, or it may merely be a phenomenon associated with the effects of venous hypertension on the AVM nidus.

Adult↗

Diffusion-weighted imaging of the spinal cord.

Spinal cord DWI may be useful in providing information not available with conventional MR imaging. More work, however, is required to explain what the qualitative and quantitative results actually represent. Computer simulations and detailed radiologic-histologic correlations will therefore be necessary.

Animals↗

Vertebrobasilar thrombolysis with intravenous tirofiban: case report.

The use of thrombolytic agents in the setting of established cerebral infarction is limited by concerns for hemorrhagic transformation. Novel thrombolytic approaches, which have received minimal consideration, may be associated with lower risks of hemorrhage. We illustrate vertebrobasilar thrombolysis with intravenous tirofiban, a selective platelet glycoprotein IIb/IIIa receptor antagonist, and discuss the potential thrombolytic properties of this class of antithrombotics.

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