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Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation

High-resolution retinotopic blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) with a wide-view presentation can be ...

Stony Brook University

: To evaluate whether  optical imaging methods and histology can detect comparable vascular and neuronal damage in the retina due to the effects of progressive chronic hypertension on the retinal vasculature and neurons using the spontaneously hypertensive rat (SHR) model at young and old ages. : Male SHR and normotensive Wistar Kyoto (WKY) rats were studied at 10 and 40 weeks of age (n = 6 each group). Arterial blood pressure was measured with a tail-cuff. Under anesthesia, fundus photography was used to measure retinal arterial diameters and optical coherence tomography was used to measure retinal layer thicknesses. Histology was then used to measure microvascular and cell density in different retinal layers. : Blood pressure was significantly higher in SHR than WKY in both age groups ( < .05). Fundus images showed no gross abnormalities, hemorrhage, or stenosis in all groups. Retinal vessels, however, appeared more tortuous in SHR compared to WKY at both ages. Retinal vessel diameters in SHR were significantly narrower than in WKY at both age groups ( < .05). Microvascular densities at 10 weeks were not significantly different ( > .05) but were markedly reduced in SHR at 40 weeks compared to WKY ( < .05). The outer nuclear layer thickness of SHR was significantly thinner than that of WKY at both ages ( < .05), consistent with histological cell density measurements ( < .05). The ganglion cell layer and inner nuclear layer thicknesses were not significantly different between SHR and WKY ( > .05), consistent with the corresponding histological cell density measurements ( > .05). :  optical imaging showed that systemic hypertension progressively reduces retinal arterial diameter and thicknesses of the outer retina in spontaneously hypertensive rats, with consistent vascular and neuronal findings from histology.

Retinal Vascular and Anatomical Features in the Spontaneously Hypertensive Rat.

The optics of the ocular lens are determined by its geometry (shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn maintained by unique cellular physiology known as the lens internal microcirculation system. Previously, magnetic resonance imaging (MRI) has been used on ex vivo organ cultured bovine lenses to show that pharmacological perturbations to this microcirculation system disrupt ionic and fluid homeostasis and overall lens optics. In this study, we have optimised in vivo MRI protocols for use on wild-type and transgenic mouse models so that the effects of genetically perturbing the lens microcirculation system on lens properties can be studied. In vivo MRI protocols and post-analysis methods for studying the mouse lens were optimised and used to measure the lens geometry, diffusion, T1 and T2, as well as the refractive index (n) calculated from T2, in wild-type mice and the genetically modified Cx50KI46 mouse. In this animal line, gap junctional coupling in the lens is increased by knocking in the gap junction protein Cx46 into the Cx50 locus. Relative to wild-type mice, Cx50KI46 mice showed significantly reduced lens size and radius of curvature, increased T1 and T2 values, and decreased n in the lens nucleus, which was consistent with the developmental and functional changes characterised previously in this lens model. These proof of principle experiments show that in vivo MRI can be applied to transgenic mouse models to gain mechanistic insights into the relationship between lens physiology and optics, and in the future suggest that longitudinal studies can be performed to determine how this relationship is altered by age in mouse models of cataract.

Multi-parametric MRI of the physiology and optics of the in-vivo mouse lens.

Chronic hypertension alters cerebrovascular function, which can lead to neurovascular pathologies and increased susceptibility to neurological disorders. The purpose of this study was to utilize in vivo MRI methods with corroborating immunohistology to evaluate neurovascular dysfunction due to progressive chronic hypertension. The spontaneously hypertensive rat (SHR) model at different stages of hypertension was studied to evaluate: i) basal cerebral blood flow (CBF), ii) cerebrovascular reactivity (CVR) assessed by CBF and blood-oxygenation level dependent (BOLD) signal changes to hypercapnia, iii) neurovascular coupling from CBF and BOLD changes to forepaw stimulation, and iv) damage of neurovascular unit (NVU) components (microvascular, astrocyte and neuron densities). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR (mild hypertension), basal CBF was higher (p < 0.05), CVR trended higher, and neurovascular coupling response was higher (p < 0.05), compared to normotensive rats. In 40-week SHR (severe hypertension), basal CBF, CVR, and neurovascular coupling response were reversed to similar or below normotensive rats, and were significantly different from 10-week SHR (p < 0.05). Immunohistological analysis found significantly reduced microvascular density, increased astrocytes, and reduced neuronal density in SHR at 40 weeks (p < 0.05) but not at 10 weeks (p > 0.05) in comparison to age-matched controls. In conclusion, we observed a bi-phasic basal CBF, CVR and neurovascular coupling response from early to late hypertension using in vivo MRI, with significant changes prior to changes in the NVU components from histology. MRI provides clinically relevant data that might be useful to characterize neurovascular pathogenesis on the brain in hypertension.

MRI study of cerebral blood flow, vascular reactivity, and vascular coupling in systemic hypertension.

Editorial for "Perfusion Analysis of Kidney Injury in Rats With Cirrhosis Induced by Common Bile Duct Ligation Using Arterial Spin Labeling MRI".

The purpose of this study was to investigate neuronal and vascular functional deficits in the retina and their association in a diabetic mouse model. We measured electroretinography (ERG) responses and choroidal and retinal blood flow (ChBF, RBF) with magnetic resonance imaging (MRI) in healthy and diabetic mice under basal conditions and under hypercapnic challenge.

Diabetic mice have retinal and choroidal blood flow deficits and electroretinogram deficits with impaired responses to hypercapnia.

To test the hypothesis that mild chronic hyperoxia treatment would improve retinal function despite a progressive decline in ocular blood flow in the DBA/2J mouse model of glaucoma.

Effects of chronic mild hyperoxia on retinal and choroidal blood flow and retinal function in the DBA/2J mouse model of glaucoma.

Abnormal intraocular fluid flow or clearance is involved with a variety of eye diseases such as glaucoma and diabetic retinopathy, but measurement of water exchange dynamics in the vitreous and aqueous remain challenging. H MRI can be used to image deuterium oxide (D₂O) as a tracer, but the signal-to-noise ratio for deuterium is low due to its low concentration, which has hampered its application to imaging the eye. To overcome this challenge, we investigated the feasibility of direct DO MRI to measure water dynamics in the mouse eye. The balanced steady-state free precession (bSSFP) sequence provided substantially higher signal-to-noise ratio for imaging DO in fluid compared to standard gradient echo and spin echo sequences. bSSFP allowed dynamic imaging of intraocular water inflow in the mouse with 41 s temporal resolution. The inflow rate in the vitreous was found to be faster than in the aqueous. These studies demonstrate the feasibility of in vivo imaging of water inflow dynamics into the both the vitreous and aqueous in mice, which could be useful in studies of abnormal fluid exchange in rodent models of eye disease.

Imaging ocular water inflow in the mouse with deuterium oxide MRI.

The purpose of this study was to utilize in vivo magnetic resonance imaging (MRI) and optical modeling to investigate how changes in water transport, lens curvature, and gradient refractive index (GRIN) alter the power of the mouse lens as a function of age.

Eric R. Muir

Department of Radiology,
School of Medicine,
Department of Radiology, School of Medicine

Stony Brook University

Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation

Eric R. Muir

Department of Radiology,School of Medicine,Department of Radiology, School of Medicine

Stony Brook University

Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation

Department of Radiology,
School of Medicine,
Department of Radiology, School of Medicine