Merging computational fluid dynamics and 4D Flow MRI using proper orthogonal decomposition and ridge regression

Time resolved phase-contrast magnetic resonance imaging 4D-PCMR (also called 4D Flow MRI) data while capable of non-invasively measuring blood velocities, can be affected by acquisition noise, flow artifacts, and resolution limits. In this paper, we present a novel method for merging 4D Flow MRI with computational fluid dynamics (CFD) to address these limitations and to reconstruct de-noised, divergence-free high-resolution flow-fields. Proper orthogonal decomposition (POD) is used to construct the orthonormal basis of the local sampling of the space of all possible solutions to the flow equations both at the low-resolution level of the 4D Flow MRI grid and the high-level resolution of the CFD mesh. Low-resolution, de-noised flow is obtained by projecting in vivo 4D Flow MRI data onto the low-resolution basis vectors. Ridge regression is then used to reconstruct high-resolution de-noised divergence-free solution. The effects of 4D Flow MRI grid resolution, and noise levels on the resulting velocity fields are further investigated. A numerical phantom of the flow through a cerebral aneurysm was used to compare the results obtained using the POD method with those obtained with the state-of-the-art de-noising methods. At the 4D Flow MRI grid resolution, the POD method was shown to preserve the small flow structures better than the other methods, while eliminating noise. Furthermore, the method was shown to successfully reconstruct details at the CFD mesh resolution not discernible at the 4D Flow MRI grid resolution. This method will improve the accuracy of the clinically relevant flow-derived parameters, such as pressure gradients and wall shear stresses, computed from in vivo 4D Flow MRI data.     

Patterns of differences in brain morphology in humans as compared to extant apes

Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups.     

Sedation Agents Differentially Modulate Cortical and Subcortical Blood Oxygenation: Evidence from Ultra-High Field MRI at 17.2 T

Background

Sedation agents affect brain hemodynamic and metabolism leading to specific modifications of the cerebral blood oxygenation level. We previously demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood oxygenation following the administration of sedation drugs commonly used in animal research. Here we applied the UHF-MRI method to study clinically relevant sedation drugs for their effects on cortical and subcortical (thalamus, striatum) oxygenation levels.

Methods

We acquired T2*-weighted images of Sprague-Dawley rat brains at 17.2T in vivo. During each MRI session, rats were first anesthetized with isoflurane, then with a second sedative agent (sevoflurane, propofol, midazolam, medetomidine or ketamine-xylazine) after stopping isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral blood oxygenation level for each sedative agent in each region of interest: cortex, hippocampus, thalamus and striatum.

Results

The T2*-oxygenation-ratio was consistent across scan sessions. This ratio was higher with inhalational agents than with intravenous agents. Under sevoflurane and medetomidine, T2*-oxygenation-ratio was homogenous across the brain regions. Intravenous agents (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in subcortical regions than in the cortex under propofol or midazolam.

Conclusion

Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood oxygenation level induced by sedative agents across brain structures. This approach also allows for a classification of sedative agents based on their differential effects on cerebral blood oxygenation level.     

The Japan Monkey Centre Primates Brain Imaging Repository for comparative neuroscience: an archive of digital records including records for endangered species

Advances in magnetic resonance imaging (MRI) and computational analysis technology have enabled comparisons among various primate brains in a three-dimensional electronic format. Results from comparative studies provide information about common features across primates and species-specific features of neuroanatomy. Investigation of various species of non-human primates is important for understanding such features, but the majority of comparative MRI studies have been based on experimental primates, such as common marmoset, macaques, and chimpanzee. A major obstacle has been the lack of a database that includes non-experimental primates’ brain MRIs. To facilitate scientific discoveries in the field of comparative neuroanatomy and brain evolution, we launched a collaborative project to develop an open-resource repository of non-human primate brain images obtained using ex vivo MRI. As an initial open resource, here we release a collection of structural MRI and diffusion tensor images obtained from 12 species: pygmy marmoset, owl monkey, white-fronted capuchin, crab-eating macaque, Japanese macaque, bonnet macaque, toque macaque, Sykes’ monkey, red-tailed monkey, Schmidt’s guenon, de Brazza’s guenon, and lar gibbon. Sixteen postmortem brain samples from the 12 species, stored in the Japan Monkey Centre (JMC), were scanned using a 9.4-T MRI scanner and made available through the JMC collaborative research program (http://www.j-monkey.jp/BIR/index_e.html). The expected significant contributions of the JMC Primates Brain Imaging Repository include (1) resources for comparative neuroscience research, (2) preservation of various primate brains, including those of endangered species, in a permanent digital form, (3) resources with higher resolution for identifying neuroanatomical features, compared to previous MRI atlases, (4) resources for optimizing methods of scanning large fixed brains, and (5) references for veterinary neuroradiology. User-initiated research projects beyond these contributions are also anticipated.     

Magnetic resonance imaging quality and volumes of brain structures from live and postmortem imaging of California sea lions with clinical signs of domoic acid toxicosis

Our goal in this study was to compare magnetic resonance images and volumes of brain structures obtained alive versus postmortem of California sea lions Zalophus californianus exhibiting clinical signs of domoic acid (DA) toxicosis and those exhibiting normal behavior. Proton density-(PD) and T2-weighted images of postmortem-intact brains, up to 48 h after death, provided similar quality to images acquired from live sea lions. Volumes of gray matter (GM) and white matter (WM) of the cerebral hemispheres were similar to volumes calculated from images acquired when the sea lions were alive. However, cerebrospinal fluid (CSF) volumes decreased due to leakage. Hippocampal volumes from postmortem-intact images were useful for diagnosing unilateral and bilateral atrophy, consequences of DA toxicosis. These volumes were similar to the volumes in the live sea lion studies, up to 48 h postmortem. Imaging formalin-fixed brains provided some information on brain structure; however, images of the hippocampus and surrounding structures were of poorer quality compared to the images acquired alive and postmortem-intact. Despite these issues, volumes of cerebral GM and WM, as well as the hippocampus, were similar to volumes calculated from images of live sea lions and sufficient to diagnose hippocampal atrophy. Thus, postmortem MRI scanning (either intact or formalin-fixed) with volumetric analysis can be used to investigate the acute, chronic and possible developmental effects of DA on the brain of California sea lions.     

A Special Phase Detector for Magnetic Inductive Measurement of Cerebral Hemorrhage

Cerebral hemorrhage is an important clinical problem that is often monitored and studied with expensive techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). These devices are not readily available in economically underdeveloped regions of the world and in emergency departments and emergency zones. The magnetic inductive method is an emerging technology that may become a new tool to detect cerebral hemorrhage. In this study, a special phase detector (PD) was developed and used for cerebral hemorrhage detection with the magnetic inductive method. The performance indicated that the PD can achieve phase noise as low as 6 m° and a 4-hour phase drift as low as 30 m° at 21.4 MHz. The noise and drift decreased as the frequency decreased. The performance at 10.7 MHz was slightly better than that of other recently developed phase detection systems. To test the practicality of the system, the PD was used to detect the volume change in a self-made physical model of the brain. The measured phase shift was approximately proportional to the volume change of physiological saline inside the model. The change of the phase shift increased as the volume change and frequency increased. The results are in agreement with those from previous reports. To verify the feasibility of in vivo detection, an autologous blood injection model was established in rabbit brain. The results from the injection group showed a similar trend of increasing phase shift change with increasing injection volume. The average phase shift change induced by a 3-ml injection of blood was 0.502°±0.119°, which was much larger than that of the control group. The measurement system can distinguish a minimal cerebral hemorrhage volume of approximately 0.5 ml. All of the results demonstrated that the PD used with this method can detect cerebral hemorrhage.     

Validating Excised Rodent Lungs for Functional Hyperpolarized Xenon-129 MRI

Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) ¹²⁹Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp ¹²⁹Xe. Straightforward hp ¹²⁹Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp ¹²⁹Xe probe volumes during the inhalation cycle. Hp ¹²⁹Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.     

Voxel-based partial volume correction of PET images via subtle MRI guided non-local means regularization

PurposePositron emission tomography (PET) images tend to be significantly degraded by the partial volume effect (PVE) resulting from the limited spatial resolution of the reconstructed images. Our purpose is to propose a partial volume correction (PVC) method to tackle this issue.MethodsIn the present work, we explore a voxel-based PVC method under the least squares framework (LS) employing anatomical non-local means (NLMA) regularization. The well-known non-local means (NLM) filter utilizes the high degree of information redundancy that typically exists in images, and is typically used to directly reduce image noise by replacing each voxel intensity with a weighted average of its non-local neighbors. Here we explore NLM as a regularization term within iterative-deconvolution model to perform PVC. Further, an anatomical-guided version of NLM was proposed that incorporates MRI information into NLM to improve resolution and suppress image noise. The proposed approach makes subtle usage of the accompanying MRI information to define a more appropriate search space within the prior model. To optimize the regularized LS objective function, we used the Gauss-Seidel (GS) algorithm with the one-step-late (OSL) technique.ResultsAfter the import of NLMA, the visual and quality results are all improved. With a visual check, we notice that NLMA reduce the noise compared to other PVC methods. This is also validated in bias-noise curve compared to non-MRI-guided PVC framework. We can see NLMA gives better bias-noise trade-off compared to other PVC methods.ConclusionsOur efforts were evaluated in the base of amyloid brain PET imaging using the BrainWeb phantom and in vivo human data. We also compared our method with other PVC methods. Overall, we demonstrated the value of introducing subtle MRI-guidance in the regularization process, the proposed NLMA method resulting in promising visual as well as quantitative performance improvements.     

Imaging performance of phase-contrast breast computed tomography with synchrotron radiation and a CdTe photon-counting detector

PurposeWithin the SYRMA-CT collaboration based at the ELETTRA synchrotron radiation (SR) facility the authors investigated the imaging performance of the phase-contrast computed tomography (CT) system dedicated to monochromatic in vivo 3D imaging of the female breast, for breast cancer diagnosis.MethodsTest objects were imaged at 38 keV using monochromatic SR and a high-resolution CdTe photon-counting detector. Signal and noise performance were evaluated using modulation transfer function (MTF) and noise power spectrum. The analysis was performed on the images obtained with the application of a phase retrieval algorithm as well as on those obtained without phase retrieval. The contrast to noise ratio (CNR) and the capability of detecting test microcalcification clusters and soft masses were investigated.ResultsFor a voxel size of (60 μm)³, images without phase retrieval showed higher spatial resolution (6.7 mm⁻¹ at 10% MTF) than corresponding images with phase retrieval (2.5 mm⁻¹). Phase retrieval produced a reduction of the noise level and an increase of the CNR by more than one order of magnitude, compared to raw phase-contrast images. Microcalcifications with a diameter down to 130 μm could be detected in both types of images.ConclusionsThe investigation on test objects indicates that breast CT with a monochromatic SR source is technically feasible in terms of spatial resolution, image noise and contrast, for in vivo 3D imaging with a dose comparable to that of two-view mammography. Images obtained with the phase retrieval algorithm showed the best performance in the trade-off between spatial resolution and image noise.     

Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue

In spite of considerable technical advance in MRI techniques, the optical resolution of these methods are still limited. Consequently, the delineation of cytoarchitectonic fields based on probabilistic maps and brain volume changes, as well as small-scale changes seen in MRI scans need to be verified by neuronanatomical/neuropathological diagnostic tools. To attend the current interdisciplinary needs of the scientific community, brain banks have to broaden their scope in order to provide high quality tissue suitable for neuroimaging- neuropathology/anatomy correlation studies. The Brain Bank of the Brazilian Aging Brain Research Group (BBBABSG) of the University of Sao Paulo Medical School (USPMS) collaborates with researchers interested in neuroimaging-neuropathological correlation studies providing brains submitted to postmortem MRI in-situ. In this paper we describe and discuss the parameters established by the BBBABSG to select and to handle brains for fine-scale neuroimaging-neuropathological correlation studies, and to exclude inappropriate/unsuitable autopsy brains. We tried to assess the impact of the postmortem time and storage of the corpse on the quality of the MRI scans and to establish fixation protocols that are the most appropriate to these correlation studies. After investigation of a total of 36 brains, postmortem interval and low body temperature proved to be the main factors determining the quality of routine MRI protocols. Perfusion fixation of the brains after autopsy by mannitol 20% followed by formalin 20% was the best method for preserving the original brain shape and volume, and for allowing further routine and immunohistochemical staining. Taken to together, these parameters offer a methodological progress in screening and processing of human postmortem tissue in order to guarantee high quality material for unbiased correlation studies and to avoid expenditures by post-imaging analyses and histological processing of brain tissue.     

An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation

We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [(11)C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [(11)C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.     

Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain

LRRK2 gain-of-function is considered a major cause of Parkinson’s disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.     

Comparison of Magnetic Resonance Imaging in Live vs. Post Mortem Rat Brains

Magnetic Resonance Imaging (MRI) is an increasingly popular technique for examining neurobiology in rodents because it is both noninvasive and nondestructive. MRI scans can be acquired from either live or post mortem specimens. In vivo scans have a key advantage in that subjects can be scanned at multiple time-points in longitudinal studies. However, repeated exposure to anesthesia and stress may confound studies. In contrast, post mortem scans offer improved image quality and increased signal-to-noise ratio (SNR) due to several key advantages: First, the images are not disrupted by motion and pulsation artifacts. Second, they allow the brain tissue to be perfused with contrast agents, enhancing tissue contrast. Third, they allow longer image acquisition times, yielding higher resolution and/or improved SNR. Fourth, they allow assessment of groups of animals at the same age without scheduling complications. Despite these advantages, researchers are often skeptical of post mortem MRI scans because of uncertainty about whether the fixation process alters the MRI measurements. To address these concerns, we present a thorough comparative study of in vivo and post mortem MRI scans in healthy male Wistar rats at three age points throughout adolescence (postnatal days 28 through 80). For each subject, an in vivo scan was acquired, followed by perfusion and two post mortem scans at two different MRI facilities. The goal was to assess robustness of measurements, to detect any changes in volumetric measurements after fixation, and to investigate any differential bias that may exist between image acquisition techniques. We present this volumetric analysis for comparison of 22 anatomical structures between in vivo and post mortem scans. No significant changes in volumetric measurements were detected; however, as hypothesized, the image quality is dramatically improved in post mortem scans. These findings illustrate the validity and utility of using post mortem scans in volumetric neurobiological studies.     

BOLD temporal dynamics of rat superior colliculus and lateral geniculate nucleus following short duration visual stimulation

Background

The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN''s response temporal dynamics following short duration (1 s) visual stimulation.

Methodology/Principal Findings

Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC.

Conclusions/Significance

The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different.     

Fluorescence-Based Monitoring of In Vivo Neural Activity Using a Circuit-Tracing Pseudorabies Virus

The study of coordinated activity in neuronal circuits has been challenging without a method to simultaneously report activity and connectivity. Here we present the first use of pseudorabies virus (PRV), which spreads through synaptically connected neurons, to express a fluorescent calcium indicator protein and monitor neuronal activity in a living animal. Fluorescence signals were proportional to action potential number and could reliably detect single action potentials in vitro. With two-photon imaging in vivo, we observed both spontaneous and stimulated activity in neurons of infected murine peripheral autonomic submandibular ganglia (SMG). We optically recorded the SMG response in the salivary circuit to direct electrical stimulation of the presynaptic axons and to physiologically relevant sensory stimulation of the oral cavity. During a time window of 48 hours after inoculation, few spontaneous transients occurred. By 72 hours, we identified more frequent and prolonged spontaneous calcium transients, suggestive of neuronal or tissue responses to infection that influence calcium signaling. Our work establishes in vivo investigation of physiological neuronal circuit activity and subsequent effects of infection with single cell resolution.     

Termination of retinofugal fibers and lamination pattern in the lateral geniculate nucleus of the gibbon

The lateral geniculate nucleus (LGN) of the gibbon (Hylobates sp.) consists of four principal layers, i.e., layers 1 and 2 containing large somata and layers 3 and 4 comprising medium-sized neurons. In addition, there are intercalated layers S, imm and imp, each consisting of small cells. Tracing of retinofugal fibers with the autoradiographic method revealed that the retina projects to the ipsilateral layers 2, 3 and imp and to the contralateral layers 1, 4, S and imm. No 'hidden' layers have been found. This type of lamination pattern sets the LGN of the gibbon apart from that of all Old World monkeys, chimpanzee and man. Retinal projections to other subcortical regions are also described.     

In vivo ankle joint kinematics from dynamic magnetic resonance imaging using a registration-based framework

In this paper, we propose a method for non-invasively measuring three-dimensional in vivo kinematics of the ankle joint from a dynamic MRI acquisition of a single range-of-motion cycle. The proposed approach relies on an intensity-based registration method to estimate motion from multi-plane dynamic MRI data. Our approach recovers not only the movement of the skeleton, but also the possibly non-rigid temporal deformation of the joint. First, the rigid motion of each ankle bone is estimated. Second, a four-dimensional (3D+time) high-resolution dynamic MRI sequence is estimated through the use of the log-euclidean framework for the computation of temporal dense deformation fields. This approach has been then applied and evaluated on in vivo dynamic MRI data acquired for a pilot study on six healthy pediatric cohort in order to establish in vivo normative joint biomechanics. Results demonstrate the robustness of the proposed pipeline and very promising high resolution visualization of the ankle joint.     

Shape (but not volume) changes in the thalami in Parkinson disease

Background  

Recent pathological studies have suggested that thalamic degeneration may represent a site of non-dopaminergic degeneration in Parkinson's Disease (PD). Our objective was to determine if changes in the thalami could be non-invasively detected in structural MRI images obtained from subjects with Parkinson disease (PD), compared to age-matched controls.     

Human ocular dominance columns as revealed by high-field functional magnetic resonance imaging.

We mapped ocular dominance columns (ODCs) in normal human subjects using high-field (4 T) functional magnetic resonance imaging (fMRI) with a segmented echo planar imaging technique and an in-plane resolution of 0.47 x 0.47 mm(2). The differential responses to left or right eye stimulation could be reliably resolved in anatomically well-defined sections of V1. The orientation and width ( approximately 1 mm) of mapped ODC stripes conformed to those previously revealed in postmortem brains stained with cytochrome oxidase. In addition, we showed that mapped ODC patterns could be largely reproduced in different experiments conducted within the same experimental session or over different sessions. Our results demonstrate that high-field fMRI can be used for studying the functions of human brains at columnar spatial resolution.     

Alteration in Glutathione Content and Associated Enzyme Activities in the Synaptic Terminals but not in the Non-synaptic Mitochondria from the Frontal Cortex of Parkinson’s Disease Brains

Altered redox dynamics contribute to physiological aging and Parkinson’s disease (PD). This is reflected in the substantia nigra (SN) of PD patients as lowered antioxidant levels and elevated oxidative damage. Contrary to this observation, we previously reported that non-SN regions such as caudate nucleus and frontal cortex (FC) exhibited elevated antioxidants and lowered mitochondrial and oxidative damage indicating constitutive protective mechanisms in PD brains. To investigate whether the sub-cellular distribution of antioxidants could contribute to these protective effects, we examined the distribution of antioxidant/oxidant markers in the neuropil fractions [synaptosomes, non-synaptic mitochondria and cytosol] of FC from PD (n = 9) and controls (n = 8). In the control FC, all the antioxidant activities [Superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), GSH-S-transferase (GST)] except glutathione reductase (GR) were the highest in cytosol, but several fold lower in mitochondria and much lower in synaptosomes. However, FC synaptosomes from PD brains had significantly higher levels of GSH (p = 0.01) and related enzymes [GPx (p = 0.02), GR (p = 0.06), GST (p = 0.0001)] compared to controls. Conversely, mitochondria from the FC of PD cases displayed elevated SOD activity (p = 0.02) while the GSH and related enzymes were relatively unaltered. These changes in the neuropil fractions were associated with unchanged or lowered oxidative damage. Further, the mitochondrial content in the synaptosomes of both PD and control brains was ≥five-fold lower compared to the non-synaptic mitochondrial fraction. Altered distribution of oxidant/antioxidant markers in the neuropil fractions of the human brain during aging and PD has implications for (1) degenerative and protective mechanisms (2) distinct antioxidant mechanisms in synaptic terminals compared to other compartments.