Biomedical subjects

Govind Nair

Publications and source records attributed to Govind Nair.

5 recordsLinked to original sources

PubMed2006

Structural and functional MRI reveals multiple retinal layers.

MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layer-specific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer/inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-level-dependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.

Aging↗

PubMed2006

Magnetic resonance imaging of tissue and vascular layers in the cat retina.

PURPOSE: To report the visual resolution of multiple cell and vascular "layers" in the cat retina using MRI. MATERIALS AND METHODS: T2- and diffusion-weighted MRI at 4.7 Tesla was performed. Layer-specific thickness, T2, spin density, apparent diffusion coefficient perpendicular (ADC(perpendicular)) and parallel (ADC(parallel)) to the retinal surface were tabulated. T1-weighted MRI was acquired before and after intravenous administration of Gd-DTPA and subtraction images were obtained. Histology was performed for validation. RESULTS: Three distinct "layers" were observed. The inner strip nearest to the vitreous (exhibiting large T2, ADC, spin density with Gd-DTPA enhancement) overlapped the ganglion cell layer, bipolar cell layer, and the embedded retinal vascular layer. The middle strip (exhibiting small T2, ADC, spin density without Gd-DTPA enhancement) overlapped the photoreceptor cell layer and the inner and outer segments. The outer strip (exhibiting large T2, ADC, spin density with Gd-DTPA enhancement) overlapped the tapetum and choroidal vascular layer. T2, spin density, ADC(perpendicular) and ADC(parallel) of different "layers" were tabulated. The inner strip was slightly thicker than the other two strips. The total thickness, including neural and nonneural retina, was 358 +/- 13 microm (N = 6) by MRI and 319 +/- 77 microm (N = 5) by histology. CONCLUSION: MRI provides a noninvasive tool to study the retina with laminar specificity without depth limitation.

Animals↗

PubMed2005

Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice.

Diffusion tensor imaging (DTI) using variable diffusion times (t(diff)) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At t(diff) = 30 ms, the diffusion anisotropy "volume ratio" (VR), diffusion perpendicular to the fibers (lambda( perpendicular)), and mean apparent diffusion coefficient ( ) of the corpus callosum of shi mice were significantly higher than those of wt mice by 12 +/- 2%, 13 +/- 2%, and 10 +/- 1%, respectively; fractional anisotropy (FA) and relative anisotropy (RA) were lower by 10 +/- 1% and 11 +/- 3%, respectively. Diffusion parallel to the fibers (lambda(//)) was not statistically different between shi and wt mice. Normalized T(2)-weighted signal intensities showed obvious differences (27 +/- 4%) between wt and shi mice in the corpus callosum but surprisingly did not detect transplant-derived myelination. In contrast, diffusion anisotropy maps detected transplant-derived myelination in the corpus callosum and its spatial distribution was consistent with the donor-derived myelination determined by immunohistochemical staining. Anisotropy indices (except lambda(//)) in the corpus callosum showed strong t(diff) dependence (30-280 ms), and the differences in lambda( perpendicular) and VR between wt and shi mice became significantly larger at longer t(diff), indicative of improved DTI sensitivity at long t(diff). In contrast, anisotropy indices in the hippocampus showed very weak t(diff) dependence and were not significantly different between wt and shi mice across different t(diff). This study provides insights into the biological signal sources and measurement parameters influencing DTI contrast, which could lead to developing more sensitive techniques for detection of demyelinating diseases.

Algorithms↗

PubMed2005

The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats.

The use of functional magnetic resonance imaging (fMRI) in animal models of cocaine addiction is an invaluable tool for investigating the neuroadaptations that lead to this psychiatric disorder. We used blood-oxygen-level-dependent (BOLD) MRI in awake rats to identify the neuronal circuits affected by repeated cocaine administration. Rats were given an injection of cocaine (15 mg/kg, i.p.) or its vehicle for 7 days, abstained from injections for 1 week, and challenged with an intracerebroventricular cocaine injection during functional imaging. Acute cocaine produced robust positive BOLD responses across well-known monoamine-enriched brain regions, such as the prefrontal cortex, nucleus accumbens, dorsal striatum, sensory cortex, hippocampus, thalamus, and midbrain areas. However, repeated cocaine administration resulted in lower BOLD responses in the prefrontal cortex, agranular insular cortex, nucleus accumbens, ventral pallidum, and dorsomedial thalamus, among other brain regions. Reductions in BOLD intensity were not associated with variations in cerebrovascular reactivity between drug naive rats and those repeatedly exposed to cocaine. Therefore, the lower metabolic activation in response to cocaine could reflect a reduced neuronal and/or synaptic activity upon repeated administration.

Animals↗

PubMed2004

Echo-planar BOLD fMRI of mice on a narrow-bore 9.4 T magnet.

The feasibility of BOLD fMRI in association with electrical somatosensory stimulation on spontaneously breathing, isoflurane-anesthetized mice was investigated using spin-echo, echo-planar imaging (EPI) on a vertical narrow-bore 9.4 T magnet. Three experiments were performed to derive an optimal fMRI protocol. In Experiment 1 (n = 9), spin-echo BOLD responses to 10% CO2 challenge under graded isoflurane (0.25-1.25%) ranged from 10 +/- 2% to 3.5 +/- 0.9%; the optimal BOLD contrast-to-noise ratio peaked at 0.75% isoflurane. In Experiment 2 (n = 6), hindpaw somatosensory stimulations using 1-7 mA under 0.75% isoflurane revealed the optimal BOLD response was at 6 mA. In Experiment 3 (n = 5), BOLD responses to 4 and 6 mA stimulation under 0.75% and 1% isoflurane were evaluated in detail, confirming the optimal conditions in Experiment 2. These results demonstrated that BOLD fMRI using single-shot, spin-echo EPI in a mouse somatosensory stimulation model could be routinely performed on high-field, vertical, narrow-bore magnets. This protocol might prove useful for fMRI studies of transgenic mice.

Anesthetics, Inhalation↗