Faculty Bibliography

Diffusion kurtosis imaging (DKI) can be used to estimate excess kurtosis, which is a dimensionless measure for the deviation of water diffusion profile from Gaussian distribution. Several recent studies have applied DKI to probe the restricted water diffusion in biological tissues. The directional analysis has also been developed to obtain the directionally specific kurtosis. However, these studies could not directly evaluate the sensitivity of DKI in detecting subtle neural tissue alterations. Brain maturation is known to involve various biological events that can affect water diffusion properties, thus providing a sensitive platform to evaluate the efficacy of DKI. In this study, in vivo DKI experiments were performed in normal Sprague-Dawley rats of 3 different ages: postnatal days 13, 31 and 120 (N=6 for each group). Regional analysis was then performed for 4 white matter (WM) and 3 gray matter (GM) structures. Diffusivity and kurtosis estimates derived from DKI were shown to be highly sensitive to the developmental changes in these chosen structures. Conventional diffusion tensor imaging (DTI) parameters were also computed using monoexponential model, yielding reduced sensitivity and directional specificity in monitoring the brain maturation changes. These results demonstrated that, by measuring directionally specific diffusivity and kurtosis, DKI offers a more comprehensive and sensitive detection of tissue microstructural changes. Such imaging advance can provide a better MR diffusion characterization of neural tissues, both WM and GM, in normal, developmental and pathological states

Glaucoma is a neurodegenerative disease of the visual system. While elevated intraocular pressure is considered to be a major risk factor, the primary cause and pathogenesis of this disease are still unclear. This study aims to employ in vivo proton magnetic resonance spectroscopy ((1)H MRS) to evaluate the metabolic changes in the visual cortex in a rat model of chronic glaucoma. Five Sprague-Dawley female rats were prepared to induce ocular hypertension unilaterally in the right eye by photocoagulating the episcleral and limbal veins using an argon laser. Single voxel (1)H MRS was performed on each side of the visual cortex 6 weeks after laser treatment. Relative to the creatine level, the choline level was found to be significantly lower in the left glaucomatous visual cortex than the right control visual cortex in all animals. In addition, a marginally significant increase in glutamate level was observed in the glaucomatous visual cortex. No apparent difference was observed between contralateral sides of the visual cortex in T1-weighted or T2-weighted imaging. The results of this study showed that glaucoma is accompanied with alterations in the metabolism of choline-containing compounds in the visual cortex contralateral to the glaucomatous rat eye. These potentially associated the pathophysiological mechanisms of glaucoma with the dysfunction of the cholinergic system in the visual pathway. (1)H MRS is a potential tool for studying the metabolic changes in glaucoma in vivo in normally appearing brain structures, and may possess direct clinical applications for humans. Measurement of the Cho:Cr reduction in the visual cortex may be a noninvasive biomarker for this disease.

This study employed blood oxygenation level-dependent functional MRI (BOLD-fMRI) to evaluate the visual responses in the superior colliculus of the developing rat brain from the time of eyelid opening to adulthood. Upon flash illumination to the contralateral eye, the regional BOLD response underwent a systematic increase in amplitude with age especially after the third postnatal week. However, no significant difference in BOLD signal increase was found between postnatal days 14 and 21. Our results constitute the first fMRI report in demonstrating the critical period of visual functions in the rat brain during maturation. This can be potentially useful in establishing the links between changes in relation to visual sensory development.

PURPOSE: To demonstrate magnetic resonance (MR) measurements of vascular lumen dynamics in common carotid arteries by using true fast imaging with steady-state precession (TrueFISP) cine imaging with an aim to provide additional physiologic information on the vessels. MATERIALS AND METHODS: The left and right common carotid arteries were studied in normal young men (N = 6; age = 21-24 years; body weight = 130-175 lbs) using electrocardiogram (ECG)-triggered TrueFISP cine imaging at 20 frames per cardiac cycle. Lumen area waveforms were characterized with specific time and amplitude ratios. Distension values were quantified. RESULTS: Distension values were measured at 25.92 +/- 2.58% and 27.58 +/- 4.44% for the left and right common carotid arteries, respectively. These findings are consistent with those previously documented using ultrasound imaging in a similar age group. Consistent lumen area waveform characteristics were found among the subjects studied. CONCLUSION: These findings demonstrate for the first time that the use of TrueFISP cine imaging is a robust, rapid technique for quantifying carotid lumen area dynamics and distension, which may be valuable in characterizing and diagnosing cardiovascular diseases

Glaucoma is a neurodegenerative disease of the visual system characterized by the elevation of intraocular pressure. While this elevated pressure is related to an increased resistance to the outflow of aqueous humor from the eye, their impacts to the etiology and pathogenesis of the disease are not fully understood. This study aims to employ in vivo Gd-DTPA enhanced magnetic resonance imaging to evaluate the ocular transport following an induction of ocular hypertension in a rat model of chronic glaucoma. An experimental ocular hypertension model was induced in adult rats using an argon laser to photocoagulate the episcleral and limbal veins on the surface of the eyeball. The enhancements of the MRI signal intensity in the anterior chamber and vitreous body were measured as a function of time following systemic administration of Gd-DTPA solution at 3 mmol/kg. Results showed a progressive T1-weighted signal increase in the vitreous body of the glaucomatous eye but not the control eye. This increase occurred earlier in the anterior vitreous body than the preretinal vitreous. Further, there was an earlier Gd-DTPA transport into the anterior chamber in the majority of glaucomatous eyes. Our findings revealed the leakage of Gd-DTPA at the aqueous-vitreous interface, which was likely resulted from increased permeability of blood-aqueous or aqueous-vitreous barrier. These may explain the sources of changing biochemical compositions in the glaucomatous chamber components, which may implicate the cascades of neurodegenerative processes in the retina and the optic nerve.

Glaucoma is a neurodegenerative disease of the visual system. While elevated intraocular pressure is considered to be a major risk factor, the primary cause and pathogenesis of the disease are still unclear. This study aims to employ in vivo manganese-enhanced magnetic resonance imaging (MEMRI) to evaluate dynamically the Mn(2+) enhancements in the visual components following an induction of ocular hypertension in a rat model of chronic glaucoma. The episcleral and limbal veins were photocoagulated unilaterally in the right eye using an argon laser to maintain a consistent elevation of intraocular pressure by about 1.6 times above the normal level. Two and six weeks after glaucoma induction, MnCl(2) solution (50 mM, 3 microL) was injected intravitreally into both eyes, and MEMRI was performed 2 to 5 h after injection. Results showed a delayed increase in T1-weighted signal intensity in the glaucomatous optic nerve at 6 weeks but not 2 weeks after glaucoma induction. In addition, there was an accumulation of Mn(2+) ions in the vitreous humour of the glaucomatous eye, with a high concentration of Mn(2+) ions at the optic nerve head and the retina. These MEMRI findings may help understand the disease mechanisms, monitor the effect of drug interventions in glaucoma models and complement the conventional techniques in examining the glaucomatous visual components.

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn(2+) injection to both ischemic models, a close pattern of T1-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn(2+) injection to the MCAO model. It is suggested that exogenous Mn(2+) injection may provide enhanced MEMRI detection of oxidative stress and gliosis early after brain ischemia. Manganese may also mediate infarctions at remote brain regions in transient focal cerebral ischemia before delayed secondary damage takes place

This study aims to employ in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate the ocular transport following an induction of ocular hypertension in a rat model of chronic glaucoma. Upon systemic administration of Gd-DTPA solution, T1-weighted signal increase was observed in the vitreous body of the glaucomatous eye but not the control eye. This increase occurred earlier in the anterior vitreous body than the preretinal vitreous. Further, there was an earlier Gd-DTPA transport into the anterior chamber in the majority of glaucomatous eyes. Our DCE-MRI findings revealed the leakage of Gd-DTPA at the aqueous-vitreous interface, which was likely resulted from increased permeability of blood-aqueous or aqueous-vitreous barrier. These may explain the sources of changing biochemical compositions in the chamber components, which may implicate the neurodegenerative processes in the glaucomatous visual components.

This study aims to employ in vivo manganese-enchanced MRI (MEMRI) to evaluate dynamically the Mn(2+) enhancements along the visual pathway following an induction of ocular hypertension in a rat model of chronic glaucoma. Results showed an accumulation of Mn(2+) ions in the vitreous humor of the glaucomatous eye, with no statistical changes in the total retinal thickness but a possible occlusion of the ions at the optic nerve head. Meanwhile, there was a reduction in Mn(2+) transport in the glaucomatous optic nerve in the later stage of our model. Fewer enhancements in the visual cortex projected from the glaucomatous eye were also detectable. These may help understand the disease mechanisms, monitor the effect of drug interventions to glaucoma models, and complement the conventional techniques in examining the visual components.