Faculty Bibliography
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105
In vivo visuotopic brain mapping with manganese-enhanced MRI and resting-state functional connectivity MRI
The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn(2+) administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn(2+) injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn(2+) transfer but not intra- or inter-hemispheric monosynaptic Mn(2+) transport after Mn(2+) injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies.
PMCID:3951771
PMID: 24394694
ISSN: 1095-9572
CID: 2449482
Successful tactile based visual sensory substitution use functions independently of visual pathway integrity
PURPOSE: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). METHODS: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). RESULTS: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p
PMCID:4026734
PMID: 24860473
ISSN: 1662-5161
CID: 2449992
In vivo chromium-enhanced MRI of the retina
Chromium (Cr) has been used histologically to stabilize lipid fractions in the retina and is suggested to enhance oxidizable lipids in brain MRI. This study explored the feasibility, sensitivity, and specificity of in vivo chromium-enhanced MRI of retinal lipids by determining its spatiotemporal profiles and toxic effect after intravitreal Cr(VI) injection to normal adult rats. One day after 3 muL Cr(VI) administration at 1-100 mM, the retina exhibited a dose-dependent increase in T1-weighted hyperintensity until 50 mM. Time-dependently, significant T1-weighted hyperintensity persisted up to 2 weeks after 10 mM Cr(VI) administration. Three-dimensional chromium-enhanced MRI of ex vivo normal eyes at isotropic 50-mum resolution showed at least five alternating bands across retinal layers, with the outermost layer being the brightest. This agreed with histology indicating alternating lipid contents with the highest level in the photoreceptor layer of the outer retina. Although Cr(VI) reduction may induce oxidative stress and depolymerize microtubules, manganese-enhanced MRI after chromium-enhanced MRI showed a dose-dependent effect of Cr toxicity on manganese uptake and axonal transport along the visual pathway. These results potentiated future longitudinal chromium-enhanced MRI studies on retinal lipid metabolism upon further optimization of Cr doses with visual cell viability.
PMID: 22213133
ISSN: 1522-2594
CID: 2449662
Effect of cerebrovascular changes on brain DTI quantitation: a hypercapnia study
Quantitative diffusion tensor imaging (DTI) offers a valuable tool to probe the microstructural changes in neural tissues in vivo, where absolute quantitation accuracy and reproducibility are essential. It has been long recognized that measurement of apparent diffusion coefficient (ADC) using DTI could be influenced by the presence of water molecules in cerebrovasculature. However, little is known about to what extent such blood signal affects DTI quantitation. In this study, we quantitatively examined the effect of cerebral hemodynamic change on DTI indices by using a standard multislice echo planar imaging (EPI) spin echo (SE) DTI acquisition protocol and a rat model of hypercapnia. In response to 5% CO(2) challenge, mean, radial and axial diffusivities measured with diffusion factor (b-value) of b=1.0 ms/mum(2) were found to increase in whole brain (1.52%+/-0.22%, 1.66%+/-0.16% and 1.35%+/-0.37%, respectively), gray matter (1.56%+/-0.23%, 1.63%+/-0.14% and 1.47%+/-0.45%, respectively) and white matter regions (1.45%+/-0.28%, 1.88%+/-0.33% and 1.10%+/-0.26%, respectively). Fractional anisotropy (FA) was found to decrease by 1.67%+/-0.38%, 1.91%+/-0.59% and 1.46%+/-0.30% in whole brain, gray matter and white matter regions, respectively. In addition, these diffusivity increases and FA decreases became more pronounced at a lower b-value (b=0.3 ms/mum(2)). The results indicated that in vivo DTI quantitation in brain can be contaminated by vascular factors on the order of few percentages. Consequently, alterations in cerebrovasculature and hemodynamics can affect the DTI quantitation and its efficacy in characterizing the neural tissue microstructures in normal and diseased states. Caution should be taken in designing and interpreting quantitative DTI studies as all DTI indices can be potentially confounded by physiologic conditions and by cerebrovascular and hemodynamic characteristics.
PMID: 22495243
ISSN: 1873-5894
CID: 2449622
High fidelity tonotopic mapping using swept source functional magnetic resonance imaging
Tonotopy, the topographic encoding of sound frequency, is the fundamental property of the auditory system. Invasive techniques lack the spatial coverage or frequency resolution to rigorously investigate tonotopy. Conventional auditory fMRI is corrupted by significant image distortion, sporadic acoustic noise and inadequate frequency resolution. We developed an efficient and high fidelity auditory fMRI method that integrates continuous frequency sweeping stimulus, distortion free MRI sequence with stable scanner noise and Fourier analysis. We demonstrated this swept source imaging (SSI) in the rat inferior colliculus and obtained tonotopic maps with ~2 kHz resolution and 40 kHz bandwidth. The results were vastly superior to those obtained by conventional fMRI mapping approach and in excellent agreement with invasive findings. We applied SSI to examine tonotopic injury following developmental noise exposure and observed that the tonotopic organization was significantly disrupted. With SSI, we also observed the subtle effects of sound pressure level on tonotopic maps, reflecting the complex neuronal responses associated with asymmetric tuning curves. This in vivo and noninvasive technique will greatly facilitate future investigation of tonotopic plasticity and disorders and auditory information processing. SSI can also be adapted to study topographic organization in other sensory systems such as retinotopy and somatotopy.
PMID: 22445952
ISSN: 1095-9572
CID: 2449632
Balanced steady-state free precession fMRI with intravascular susceptibility contrast agent
One major challenge in echo planar imaging-based functional MRI (fMRI) is the susceptibility-induced image distortion. In this study, a new cerebral blood volume-weighted fMRI technique using distortion-free balanced steady-state free precession (bSSFP) sequence was proposed and its feasibility was investigated in rat brain at 7 Tesla. After administration of intravascular susceptibility contrast agent (monocrystalline iron oxide nanoparticle [MION] at 15 mg/kg), unilateral visual stimulation was presented using a block-design paradigm. With repetition time/echo time = 3.8/1.9 ms and alpha = 18 degrees , bSSFP fMRI was performed and compared with the conventional cerebral blood volume-weighted fMRI using post-MION gradient echo and spin echo echo planar imaging. The results showed that post-MION bSSFP fMRI provides comparable sensitivity but with no severe image distortion and signal dropout. Robust negative responses were observed during stimulation and activation patterns were in excellent agreement with known neuroanatomy. Furthermore, the post-MION bSSFP signal was observed to decrease significantly during hypercapnia challenge, indicating its sensitivity to cerebral blood volume changes. These findings demonstrated that post-MION bSSFP fMRI is a promising alternative to conventional cerebral blood volume-weighted fMRI. This technique is particularly suited for fMRI investigation of animal models at high field.
PMID: 22127794
ISSN: 1522-2594
CID: 2449682
BOLD fMRI investigation of the rat auditory pathway and tonotopic organization
Rodents share general anatomical, physiological and behavioral features in the central auditory system with humans. In this study, monaural broadband noise and pure tone sounds are presented to normal rats and the resulting hemodynamic responses are measured with blood oxygenation level-dependent (BOLD) fMRI using a standard spin-echo echo planar imaging sequence (without sparse temporal sampling). The cochlear nucleus (CN), superior olivary complex, lateral lemniscus, inferior colliculus (IC), medial geniculate body and primary auditory cortex, all major auditory structures, are activated by broadband stimulation. The CN and IC BOLD signal changes increase monotonically with sound pressure level. Pure tone stimulation with three distinct frequencies (7, 20 and 40 kHz) reveals the tonotopic organization of the IC. The activated regions shift from dorsolateral to ventromedial IC with increasing frequency. These results agree with electrophysiology and immunohistochemistry findings, indicating the feasibility of auditory fMRI in rats. This is the first fMRI study of the rodent ascending auditory pathway.
PMID: 22297205
ISSN: 1095-9572
CID: 2449642
In vivo evaluation of retinal and callosal projections in early postnatal development and plasticity using manganese-enhanced MRI and diffusion tensor imaging
The rodents are an excellent model for understanding the development and plasticity of the visual system. In this study, we explored the feasibility of Mn-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) at 7 T for in vivo and longitudinal assessments of the retinal and callosal pathways in normal neonatal rodent brains and after early postnatal visual impairments. Along the retinal pathways, unilateral intravitreal Mn2+ injection resulted in Mn2+ uptake and transport in normal neonatal visual brains at postnatal days (P) 1, 5 and 10 with faster Mn2+ clearance than the adult brains at P60. The reorganization of retinocollicular projections was also detected by significant Mn2+ enhancement by 2%-10% in the ipsilateral superior colliculus (SC) of normal neonatal rats, normal adult mice and adult rats after neonatal monocular enucleation (ME) but not in normal adult rats or adult rats after monocular deprivation (MD). DTI showed a significantly higher fractional anisotropy (FA) by 21% in the optic nerve projected from the remaining eye of ME rats compared to normal rats at 6 weeks old, likely as a result of the retention of axons from the ipsilaterally uncrossed retinal ganglion cells, whereas the anterior and posterior retinal pathways projected from the enucleated or deprived eyes possessed lower FA after neonatal binocular enucleation (BE), ME and MD by 22%-56%, 18%-46% and 11%-15% respectively compared to normal rats, indicative of neurodegeneration or immaturity of white matter tracts. Along the visual callosal pathways, intracortical Mn2+ injection to the visual cortex of BE rats enhanced a larger projection volume by about 74% in the V1/V2 transition zone of the contralateral hemisphere compared to normal rats, without apparent DTI parametric changes in the splenium of corpus callosum. This suggested an adaptive change in interhemispheric connections and spatial specificity in the visual cortex upon early blindness. The results of this study may help determine the mechanisms of axonal uptake and transport, microstructural reorganization and functional activities in the living visual brains during development, diseases, plasticity and early interventions in a global and longitudinal setting.
PMID: 21985904
ISSN: 1095-9572
CID: 2449692
Conference Proceedings (IEEE Engineering in Medicine & Biology Society). 2012:2012:432-5.DOI: 10.1109/EMBC.2012.6345960
Tract-based spatial statistics (TBSS): application to detecting white matter tract variation in mild hypoxic-ischemic neonates
The aim of this study is to employ tract-based spatial statistics (TBSS) to analyze the voxel-wise differences in DTI parameters between normal and mild hypoxic-ischemic (HI) neonatal brains. Forty-one full term neonates (24 normal controls and 17 with mild HI injury) and 31 preterm neonates (20 normal controls and 11 with mild HI injury) underwent T1 weighted imaging, T2 weighted imaging and diffusion tensor imaging (DTI) within 28 days after birth. The voxel differences of fractional anisotropy (FA), lambda1, lambda2, and lambda3 values between mild HI group and control group were analyzed in preterm and full term neonates respectively. The significantly decreased FA with increased lambda2, lambda3 in corticospinal tract, genu of corpus callosum (GCC), external capsule (EC) and splenium of the corpus callosum (SCC) in mild HI neonates suggested deficits or delays in both myelination and premyelination. Such impaired corticospinal tract, in both preterm and term neonates, may directly lead to the subsequent poor motor performance. Impaired EC and SCC, the additional injured sites observed in full term neonates with mild HI injury, may be causally responsible for the dysfunction in coordination and integration. In conclusion, TBSS provides an objective, independent and sensitive method for DTI data analysis of neonatal white matter alterations after mild HI injury.
PMID: 23365921
ISSN: 1557-170x
CID: 2449612
Conference Proceedings (IEEE Engineering in Medicine & Biology Society). 2012:2012:2298-301.DOI: 10.1109/EMBC.2012.6346422
Diffusion kurtosis imaging with tract-based spatial statistics reveals white matter alterations in preschool children
Diffusion kurtosis imaging (DKI), an extension of diffusion tensor imaging (DTI), provides a practical method to describe non-Gaussian water diffusion in neural tissues. The sensitivity of DKI to detect the subtle changes in several chosen brain structures has been studied. However, intuitive and holistic methods to validate the merits of DKI remain to be explored. In this paper, tract-based spatial statistics (TBSS) was used to demonstrate white matter alterations in both DKI and DTI parameters in preschool children (1-6 years; n=10). Correlation analysis was also performed in multiple regions of interest (ROIs). Fractional anisotropy, mean kurtosis, axial kurtosis and radial kurtosis increased with age, while mean diffusivity and radial diffusivity decreased significantly with age. Fractional anisotropy of kurtosis and axial diffusivity were found to be less sensitive to the changes with age. These preliminary findings indicated that TBSS could be used to detect subtle changes of DKI parameters on the white matter tract. Kurtosis parameters, except fractional anisotropy of kurtosis, demonstrated higher sensitivity than DTI parameters. TBSS may be a convenient method to yield higher sensitivity of DKI.
PMID: 23366383
ISSN: 1557-170x
CID: 2449592
