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Plasticity in the brain is impacted by an individual’s age at the onset of the blindness. However, what drives the varying degrees of plasticity remains largely unclear. One possible explanation attributes the mechanisms for the differing levels of plasticity to the cholinergic signals originating in the nucleus basalis of Meynert. This explanation is based on the fact that the nucleus basalis of Meynert can modulate cortical processes such as plasticity and sensory encoding through its widespread cholinergic projections. Nevertheless, there is no direct evidence indicating that the nucleus basalis of Meynert undergoes plastic changes following blindness. Therefore, using multiparametric magnetic resonance imaging, we examined if the structural and functional properties of the nucleus basalis of Meynert differ between early blind, late blind and sighted individuals. We observed that early and late blind individuals had a preserved volumetric size and cerebrovascular reactivity in the nucleus basalis of Meynert. However, we observed a reduction in the directionality of water diffusion in both early and late blind individuals compared to sighted individuals. Notably, the nucleus basalis of Meynert presented diverging patterns of functional connectivity between early and late blind individuals. This functional connectivity was enhanced at both global and local (visual, language and default-mode networks) levels in the early blind individuals, but there were little-to-no changes in the late blind individuals when compared to sighted controls. Furthermore, the age at onset of blindness predicted both global and local functional connectivity. These results suggest that upon reduced directionality of water diffusion in the nucleus basalis of Meynert, cholinergic influence may be stronger for the early blind compared to the late blind individuals. Our findings are important to unravelling why early blind individuals present stronger and more widespread cross-modal plasticity compared to late blind individuals.

PURPOSE: Inversion algorithms used to convert acquired MR elastography wave data into material property estimates often assume that the underlying materials are locally homogeneous. Here we evaluate the impact of that assumption on stiffness estimates in gray-matter regions of interest in brain MR elastography. METHODS: We describe an updated neural network inversion framework using finite-difference model–derived data to train convolutional neural network inversion algorithms. Neural network inversions trained on homogeneous simulations (homogeneous learned inversions [HLIs]) or inhomogeneous simulations (inhomogeneous learned inversions [ILIs]) are generated with a variety of kernel sizes. These inversions are evaluated in a brain MR elastography simulation experiment and in vivo in a test–retest repeatability experiment including 10 healthy volunteers. RESULTS: In simulation and in vivo, HLI and ILI with small kernels produce similar results. As kernel size increases, the assumption of homogeneity has a larger effect, and HLI and ILI stiffness estimates show larger differences. At each inversion’s optimal kernel size in simulation (7 × 7 × 7 for HLI, 11 × 11 × 11 for ILI), ILI is more sensitive to true changes in stiffness in gray-matter regions of interest in simulation. In vivo, there is no difference in the region-level repeatability of stiffness estimates between the inversions, although ILI appears to better maintain the stiffness map structure as kernel size increases, while decreasing the spatial variance in stiffness estimates. CONCLUSIONS: This study suggests that inhomogeneous inversions provide small but significant benefits even when large stiffness gradients are absent.

Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy.To evaluate for change in FES size and pituitary height after shunt placement in iNPH.Retrospective.A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls.1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w.FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls.Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P 0.05.Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mmDecrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics.3 TECHNICAL EFFICACY: Stage 2.

OBJECTIVES The aim of this study was to perform a whole-brain analysis of alterations in brain mechanical properties due to normal pressure hydrocephalus (NPH). MATERIALS AND METHODS Magnetic resonance elastography (MRE) examinations were performed on 85 participants, including 44 cognitively unimpaired controls, 33 with NPH, and 8 who were amyloid-positive with Alzheimer clinical syndrome. A custom neural network inversion was used to estimate stiffness and damping ratio from patches of displacement data, accounting for edges by training the network to estimate the mechanical properties in the presence of missing data. This learned inversion was first compared with a standard analytical approach in simulation experiments and then applied to the in vivo MRE measurements. The effect of NPH on the mechanical properties was then assessed by voxel-wise modeling of the stiffness and damping ratio maps. Finally, a pattern analysis was performed on each individual's mechanical property maps by computing the correlation between each person's maps with the expected NPH effect. These features were used to fit a classifier and assess diagnostic accuracy. RESULTS The voxel-wise analysis of the in vivo mechanical property maps revealed a unique pattern in participants with NPH, including a concentric pattern of stiffening near the dural surface and softening near the ventricles, as well as decreased damping ratio predominantly in superior regions of the white matter (family-wise error corrected P < 0.05 at cluster level). The pattern of viscoelastic changes in each participant predicted NPH status in this cohort, separating participants with NPH from the control and the amyloid-positive with Alzheimer clinical syndrome groups, with areas under the receiver operating characteristic curve of 0.999 and 1, respectively. CONCLUSIONS This study provides motivation for further development of the neural network inversion framework and demonstrates the potential of MRE as a novel tool to diagnose NPH and provide a window into its pathogenesis.

Localized regions of left-right image intensity asymmetry (LRIA) were incidentally observed on TTo investigate whether systematic LRIA exist for a range of scanner models and to determine if LRIA can introduce diagnostic uncertainty.A retrospective study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data base.One thousand seven hundred fifty-three (median age: 72, males/females: 878/875) unique participants with longitudinal data were included.3T.TLRIA was calculated as the left-right percent difference with respect to the mean intensity from automated anatomical atlas segmented regions. Three neuroradiologists with 37 (**), 32 (**), and 3 (**) years of experience rated the clinical impact of 30 TFor each image type, a linear mixed effects model was fit using LRIA scores from all scanners, regions, and participants as the outcome and age and sex as predictors. Statistical significance was defined as having a P-value0.05.LRIA scores were significantly different from zero on most scanners. All clinicians were uncertain or recommended definite diagnostic follow-up in 62.5% of cases with LRIA10%. Individuals with acute brain pathology or focal neurologic deficits are not enrolled in ADNI; therefore, focal signal abnormalities were considered false positives.LRIA is system specific, systematic, creates diagnostic uncertainty, and impacts IR-SPGR, MP-RAGE, and LT-FSE-IR product sequences.2 Technical Efficacy Stage: 3.

Plasticity in the brain is differentially affected by age of blindness onset. One possible, but not yet identified mechanism is that the cholinergic signals originating from the nucleus basalis of Meynert may underlie differential extent of plasticity in early and late blind individuals. This prospect is based on the fact that the nucleus basalis of Meynert modulates cortical processes such as plasticity and sensory encoding and that the degree of cross-modal plasticity varies depending on the age of blindness onset. However, this question yet remains largely unclear. Here, we tested whether the early and late blind individuals develop dissociable plasticity in the nucleus basalis of Meynert using multi-parametric magnetic resonance imaging. We found the relatively preserved volumetric size and cerebrovascular reactivity, but significant disruption in the white matter integrity of the nucleus basalis of Meynert in both early and late blind individuals. Critically, despite its reduction in the white matter integrity, the nucleus basalis of Meynert of early blind individuals presented greater global and network functional connectivity including visual, language, and default-mode networks. Such changes in the functional connectivity were not observed in the late-blind individuals. Further, less duration of the visual experience was associated with greater global and network functional connectivity. These results indicate that the nucleus basalis of Meynert is differentially involved in the plasticity of early and late blind individuals – a similar amount of reduction in microstructural integrity in early and late blind individuals, but stronger and more widespread functional connectivity of the NBM in the early blind individuals. Our findings suggest that the nucleus basalis of Meynert may develop greater cholinergic influence on the cortex of early blind individuals. Such change may explain why early blind individuals present stronger and more widespread cross-modal plasticity during non-visual tasks compared to late blind individuals.

BackgroundThe COVID-19 pandemic presents a significant challenge to minimize mortality and hospitalizations due to this disease. Vaccinations have begun to roll-out; however, restriction policies required during and after the rollout remain uncertain. A susceptible-exposed-infected-recovered (SEIR) model was developed for Nova Scotia, and it accounted for the province’s policy interventions, demographics, and vaccine rollout schedule.MethodsA modified SEIR model was developed to simulate the spread and outcomes from COVID-19 in Nova Scotia under different policy options. The model incorporated the age distribution and co-morbidity of the province. A system dynamics model was developed in Vensim. Several scenarios were run to determine the effects of various policy options and loosening of restrictions during and after the vaccine roll-out period.ResultsWhen restrictions policy include moderate closure of businesses, restricting travel to Atlantic Canada, and the mandating of masks and physical distancing, the number of cumulative infections after 110 days was less than 120. However, if national travel was opened by July 5 2021 and there were no restrictions by September 2021, the number of active infections will peak at 6,114 by February 16 2022, and there will be a peak of 104 hospitalizations on February 16 2022. Immediate opening of travel and all restrictions on March 15, 2021 will result in 71,731 active infections by June 4 2021.DiscussionModerate restrictions will be required even after the population is fully vaccinated in order to avoid a large number of infections and hospitalizations because herd immunity is not reached due to children under 12 not being vaccinated, the efficacy of the vaccine, and the portion of the population that will choose not to be vaccinated.

Glaucoma is a neurodegenerative disease that causes progressive, irreversible vision loss. Currently, intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, glaucomatous degeneration may continue despite adequate IOP control. Therefore, there exists a need for treatment that protects the visual system, independent of IOP. This study sought, first, to longitudinally examine the neurobehavioral effects of different magnitudes and durations of IOP elevation using multi-parametric magnetic resonance imaging (MRI), optokinetics and histology; and, second, to evaluate the effects of oral citicoline treatment as a neurotherapeutic in experimental glaucoma. Eighty-two adult Long Evans rats were divided into six groups: acute (mild or severe) IOP elevation, chronic (citicoline-treated or untreated) IOP elevation, and sham (acute or chronic) controls. We found that increasing magnitudes and durations of IOP elevation differentially altered structural and functional brain connectivity and visuomotor behavior, as indicated by decreases in fractional anisotropy in diffusion tensor MRI, magnetization transfer ratios in magnetization transfer MRI, T1-weighted MRI enhancement of anterograde manganese transport, resting-state functional connectivity, visual acuity, and neurofilament and myelin staining along the visual pathway. Furthermore, 3 weeks of oral citicoline treatment in the setting of chronic IOP elevation significantly reduced visual brain integrity loss and visual acuity decline without altering IOP. Such effects sustained after treatment was discontinued for another 3 weeks. These results not only illuminate the close interplay between eye, brain, and behavior in glaucomatous neurodegeneration, but also support a role for citicoline in protecting neural tissues and visual function in glaucoma beyond IOP control. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01033-6.

Disruption of mental functions in Alzheimer’s disease (AD) and related disorders is accompanied by selective degeneration of brain regions for unknown reasons. These regions comprise large-scale ensembles of cells organized into networks required for mental functioning. A mechanistic framework does not exist to explain the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and the functional connectome. The association between dementia symptoms and degenerative brain anatomy encodes a mapping between mental functions and neuroanatomy. We isolated this mapping through unsupervised decoding of neurodegeneration in humans. This reflected a simple information processing-based functional description of macroscale brain anatomy, the global functional state space (GFSS). We then linked the GFSS to AD physiology, functional networks, and mental abilities. We extended the GFSS framework to normal aging and seven degenerative diseases of mental functions.One Sentence SummaryA global information processing framework for mental functions links neuroanatomy, cognitive neuroscience and clinical neurology.

Purpose To develop a novel magnetic resonance elastography (MRE) acquisition using a hybrid radial EPI readout scheme (TURBINE), and to demonstrate its feasibility to obtain wave images and stiffness maps in a phantom and in vivo brain. Method The proposed 3D TURBINE-MRE is based on a spoiled gradient-echo MRE sequence with the EPI readout radially rotating about the phase-encoding axis to sample a full 3D k-space. A polyvinyl chloride phantom and 6 volunteers were scanned on a compact 3T GE scanner with a 32-channel head coil at 80 Hz and 60 Hz external vibration, respectively. For comparison, a standard 2D, multislice, spin-echo (SE) EPI-MRE acquisition was also performed with the same motion encoding and resolution. The TURBINE-MRE images were off-line reconstructed with iterative SENSE algorithm. The regional ROI analysis was performed on the 6 volunteers, and the median stiffness values were compared between SE-EPI-MRE and TURBINE-MRE. Results The 3D wave-field images and the generated stiffness maps were comparable between TURBINE-MRE and standard SE-EPI-MRE for the phantom and the volunteers. The Bland-Altman plot showed no significant difference in the median regional stiffness values between the two methods. The stiffness measured with the 2 methods had a strong linear relationship with a Pearson correlation coefficient of 0.943. Conclusion We demonstrated the feasibility of the new TURBINE-MRE sequence for acquiring the desired 3D wave-field data and stiffness maps in a phantom and in-vivo brains. This pilot study encourages further exploration of TURBINE-MRE for functional MRE, free-breathing abdominal MRE, and cardiac MRE applications.

Functional imaging of spontaneous activity continues to play an important role in the field of connectomics. The most common imaging signal used for these experiments is the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal, but how this signal relates to spontaneous neuronal activity remains incompletely understood. Genetically encoded calcium indicators represent a promising tool to study this problem, as they can provide brain-wide measurements of neuronal activity compared to point measurements afforded by electrophysiological recordings. However, the relationship between the calcium signal and neurophysiological parameters at the mesoscopic scale requires further systematic characterization. Therefore, we collected simultaneous resting-state measurements of electrophysiology, along with calcium and hemodynamic imaging, in lightly anesthetized mice to investigate two aims. First, we examined the relationship between each imaging signal and the simultaneously recorded electrophysiological signal in a single brain region, finding that both signals are better correlated with multi-unit activity compared to local field potentials, with the calcium signal possessing greater signal-to-noise ratio and regional specificity. Second, we used the resting-state imaging data to model the relationship between the calcium and hemodynamic signals across the brain. We found that this relationship varied across brain regions in a way that is consistent across animals, with delays increasing by 0.6 sec towards posterior cortical regions. Furthermore, while overall functional connectivity (FC) measured by the hemodynamic signal is significantly correlated with FC measured by calcium, the two estimates were found to be significantly different. We hypothesize that these differences arise at least in part from the observed regional variation in the hemodynamic response. In total, this work highlights some of the caveats needed in interpreting hemodynamic-based measurements of FC, as well as the need for improved modeling methods to reduce this potential source of bias.

Purpose To investigate the feasibility of using artificial neural networks to estimate stiffness from MR elastography (MRE) data. Methods Artificial neural networks were fit using model-based training patterns to estimate stiffness from images of displacement using a patch size of ∼1 cm in each dimension. These neural network inversions (NNIs) were then evaluated in a set of simulation experiments designed to investigate the effects of wave interference and noise on NNI accuracy. NNI was also tested in vivo, comparing NNI results against currently used methods. Results In 4 simulation experiments, NNI performed as well or better than direct inversion (DI) for predicting the known stiffness of the data. Summary NNI results were also shown to be significantly correlated with DI results in the liver (R2 = 0.974) and in the brain (R2 = 0.915), and also correlated with established biological effects including fibrosis stage in the liver and age in the brain. Finally, repeatability error was lower in the brain using NNI compared to DI, and voxel-wise modeling using NNI stiffness maps detected larger effects than using DI maps with similar levels of smoothing. Conclusion Artificial neural networks represent a new approach to inversion of MRE data. Summary results from NNI and DI are highly correlated and both are capable of detecting biologically relevant signals. Preliminary evidence suggests that NNI stiffness estimates may be more resistant to noise than an algebraic DI approach. Taken together, these results merit future investigation into NNIs to improve the estimation of stiffness in small regions. Magn Reson Med 80:351-360, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Functional MRI (fMRI) is a popular and important tool for noninvasive mapping of neural activity. As fMRI measures the hemodynamic response, the resulting activation maps do not perfectly reflect the underlying neural activity. The purpose of this work was to design a data-driven model to improve the spatial accuracy of fMRI maps in the rat olfactory bulb. This system is an ideal choice for this investigation since the bulb circuit is well characterized, allowing for an accurate definition of activity patterns in order to train the model. We generated models for both cerebral blood volume weighted (CBVw) and blood oxygen level dependent (BOLD) fMRI data. The results indicate that the spatial accuracy of the activation maps is either significantly improved or at worst not significantly different when using the learned models compared to a conventional general linear model approach, particularly for BOLD images and activity patterns involving deep layers of the bulb. Furthermore, the activation maps computed by CBVw and BOLD data show increased agreement when using the learned models, lending more confidence to their accuracy. The models presented here could have an immediate impact on studies of the olfactory bulb, but perhaps more importantly, demonstrate the potential for similar flexible, data-driven models to improve the quality of activation maps calculated using fMRI data.

Visual sensory substitution devices provide a non-surgical and flexible approach to vision rehabilitation in the blind. These devices convert images taken by a camera into cross-modal sensory signals that are presented as a surrogate for direct visual input. While previous work has demonstrated that the visual cortex of blind subjects is recruited during sensory substitution, the cognitive basis of this activation remains incompletely understood. To test the hypothesis that top-down input provides a significant contribution to this activation, we performed functional MRI scanning in 11 blind (7 acquired and 4 congenital) and 11 sighted subjects under two conditions: passive listening of image-encoded soundscapes before sensory substitution training and active interpretation of the same auditory sensory substitution signals after a 10-minute training session. We found that the modulation of visual cortex activity due to active interpretation was significantly stronger in the blind over sighted subjects. In addition, congenitally blind subjects showed stronger task-induced modulation in the visual cortex than acquired blind subjects. In a parallel experiment, we scanned 18 blind (11 acquired and 7 congenital) and 18 sighted subjects at rest to investigate alterations in functional connectivity due to visual deprivation. The results demonstrated that visual cortex connectivity of the blind shifted away from sensory networks and toward known areas of top-down input. Taken together, our data support the model of the brain, including the visual system, as a highly flexible task-based and not sensory-based machine.

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI.SIGNIFICANCE STATEMENTFunctional magnetic resonance imaging (fMRI) is a noninvasive,in vivotechnique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it measures neuronal activity indirectly by way of the vascular response. It is currently unclear how finely the hemodynamic response is regulated within single cortical layers and whether increased inhibitory neuronal activities affect fMRI signal changes. Both laminar specificity and the neural origins of fMRI are important to interpret functional maps properly, which we investigated by activating discrete rat olfactory bulb circuits.

Purpose To test the hypothesis that removing the assumption of material homogeneity will improve the spatial accuracy of stiffness estimates made by Magnetic Resonance Elastography (MRE). Methods An artificial neural network was trained using synthetic wave data computed using a coupled harmonic oscillator model. Material properties were allowed to vary in a piecewise smooth pattern. This neural network inversion (Inhomogeneous Learned Inversion (ILI)) was compared against a previous homogeneous neural network inversion (Homogeneous Learned Inversion (HLI)) and conventional direct inversion (DI) in simulation, phantom, and in-vivo experiments. Results In simulation experiments, ILI was more accurate than HLI and DI in predicting the stiffness of an inclusion in noise-free, low-noise, and high-noise data. In the phantom experiment, ILI delineated inclusions ≤ 2.25 cm in diameter more clearly than HLI and DI, and provided a higher contrast-to-noise ratio for all inclusions. In a series of stiff brain tumors, ILI shows sharper stiffness transitions at the edges of tumors than the other inversions evaluated. Conclusion ILI is an artificial neural network based framework for MRE inversion that does not assume homogeneity in material stiffness. Preliminary results suggest that it provides more accurate stiffness estimates and better contrast in small inclusions and at large stiffness gradients than existing algorithms that assume local homogeneity. These results support the need for continued exploration of learning-based approaches to MRE inversion, particularly for applications where high resolution is required.

To investigate the use of MR elastography (MRE)–derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between “not-NASH” and “definite-NASH.” “Borderline-NASH” prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80–92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Objective: To determine antemortem MRI findings associated with microinfarcts at autopsy. Methods: Patients with microinfarcts (n = 22) and patients without microinfarcts (n = 44) who underwent antemortem MRI were identified from a dementia clinic–based, population–based, and community clinic–based autopsy cohort. The microinfarct and no-microinfarct groups were matched on age at MRI, age at death, sex, APOE status, Mini-Mental State Examination score, and pathologic diagnosis of Alzheimer disease. Brain infarcts were assessed on fluid-attenuated inversion recovery (FLAIR) MRI. White matter hyperintensities on FLAIR MRI and hippocampal volumes on T1-weighted MRI were quantified using automated methods. A subset of subjects with microinfarcts (n = 15) and a matched group of subjects without microinfarcts (n = 15) had serial T1-weighted MRIs and were included in an analysis of global and regional brain atrophy rates using automated methods. Results: The presence of cortical ( p = 0.03) and subcortical ( p = 0.02) infarcts on antemortem MRI was associated with presence of microinfarcts at autopsy. Higher numbers of cortical ( p = 0.05) and subcortical ( p = 0.03) infarcts on antemortem MRI were also associated with presence of microinfarcts. Presence of microinfarcts was not associated with white matter hyperintensities and cross-sectional hippocampal volume on antemortem MRI. Whole-brain and regional precuneus, motor, and somatosensory atrophy rates were higher in subjects with microinfarcts compared to subjects without microinfarcts. Conclusions: Microinfarcts increase brain atrophy rates independent of Alzheimer disease pathology. Association between microinfarct pathology and macroinfarcts on MRI suggests either common risk factors or a shared pathophysiology and potentially common preventive targets.

Human visual performance has been observed to show superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine whether the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI, respectively, in 15 healthy individuals at 3 T. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing.

Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans. Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life (Kupers and Ptito, 2014). More recent studies explored what happens to the visual pathways in the context of acquired blindness. This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly. Our lab and others have demonstrated compromised visual pathway integrity in those with peri-natal and acquired blindness (Schoth et al., 2006; Chan et al., 2012; Li et al., 2013; Lee et al., 2014; Dietrich et al., 2015; Ho et al., 2015; Reislev et al., 2015). Additional studies have begun to examine the changes occurring with certain disease states: patients suffering from retinitis pigmentosa, optic neuritis, and glaucoma, all so far demonstrate deterioration of the white matter tract architecture as a function of disease severity (Garaci et al., 2009; Gabilondo et al., 2014; Ohno et al., 2015). This evidence indicates that the visual system as a whole is profoundly susceptible to degeneration even with small amounts of vision loss. On the surface, these investigations appear to have negative implications for vision restoration efforts. Yet, parallel studies which examine the phenomenon of cross-modal plasticity suggest that a remodeling of the central nervous system is possible, such that areas of the brain which have been deprived of normal afferent input are able to reconstitute themselves to be receptive to alternative sensory channels (Merabet and Pascual-Leone, 2010; Kupers and Ptito, 2014). The literature includes several examples of investigations which show that the visual cortex will react to tactile and auditory stimuli in the blind but will be less readily recruited in sighted patients (Merabet and Pascual-Leone, 2010). Moreover, cross-modal interactions have been demonstrated well beyond the traditional “critical period” and into late adulthood, albeit perhaps in a less robust fashion (Sadato et al., 2002; Bedny et al., 2012; Collignon et al., 2013). The notion that the adult brain is still capable of significant structural and functional remodeling after vision loss provides opportunities to restore vision through mechanical or biological means.

As a nonsurgical treatment for malignant hepatic tumors, percutaneous tumor thermal ablation requires accurate monitor and evaluation of cell death during and after the treatment, because if sufficient ablation is not achieved on tumors, then they can progress after treatment. Currently there is not a single effective way available to accurately monitor cell death during and after in vivo thermal ablation. For the first time, we used MR elastography with a new inertial driver to repeatedly measure tissue stiffness during and after in vivo laser ablation on porcine livers. During 2-minute ablations using 4.5-, 7.5- and 15-W laser power, the stiffness of the lesion underwent very complicated changes indicative of the dynamic protein folding and unfolding that occurred under the different levels of heating. After laser ablations of a lethal dose (2 min, 15 W), lesion stiffnesses were significantly greater than the baseline values (p < 0.007) and became stiffer over time; also, the mean [95% CI] stiffness increments from baseline were significantly greater than those after lower dose (2 min, 7.5-W) laser ablations (64.4% [32.8%, 96.0%] vs 22.5% [16.3%, 28.6%], p = 0.009), which reflected the irreversible cell denaturation during the laser ablation with the lethal dose.

Objective: To investigate MRI and proton magnetic resonance spectroscopy (MRS) predictors of mild cognitive impairment (MCI) in cognitively normal older adults. Methods: Subjects were cognitively normal older adults (n = 1,156) who participated in the population-based Mayo Clinic Study of Aging MRI/MRS study from August 2005 to December 2010 and had at least one annual clinical follow-up. Single-voxel MRS was performed from the posterior cingulate gyri, and hippocampal volumes and white matter hyperintensity volumes were quantified using automated methods. Brain infarcts were assessed on MRI. Cox proportional hazards regression, with age as the time scale, was used to assess the effect of MRI and MRS markers on the risk of progression from cognitively normal to MCI. Linear mixed-effects models were used to assess the effect of MRI and MRS markers on cognitive decline. Results: After a median follow-up of 2.8 years, 214 participants had progressed to MCI or dementia (estimated incidence rate = 6.1% per year; 95% confidence interval = 5.3%–7.0%). In univariable modeling, hippocampal volume, white matter hyperintensity volume, and N -acetylaspartate/ myo -inositol were significant predictors of MCI in cognitively normal older adults. In multivariable modeling, only decreased hippocampal volume and N -acetylaspartate/ myo -inositol were independent predictors of MCI. These MRI/MRS predictors of MCI as well as infarcts were associated with cognitive decline ( p Conclusion: Quantitative MRI and MRS markers predict progression to MCI and cognitive decline in cognitively normal older adults. MRS may contribute to the assessment of preclinical dementia pathologies by capturing neurodegenerative changes that are not detected by hippocampal volumetry.

Object The object of this study was to determine the potential of magnetic resonance elastography (MRE) to preoperatively assess the stiffness of meningiomas. Methods Thirteen patients with meningiomas underwent 3D brain MRE examination to measure stiffness in the tumor as well as in surrounding brain tissue. Blinded to the MRE results, neurosurgeons made a qualitative assessment of tumor stiffness at the time of resection. The ability of MRE to predict the surgical assessment of stiffness was tested using a Spearman rank correlation. Results One case was excluded due to a small tumor size. In the remaining 12 cases, both tumor stiffness alone (p = 0.023) and the ratio of tumor stiffness to surrounding brain tissue stiffness (p = 0.0032) significantly correlated with the surgeons' qualitative assessment of tumor stiffness. Results of the MRE examination provided a stronger correlation with the surgical assessment of stiffness compared with traditional T1- and T2-weighted imaging (p = 0.089), particularly when considering meningiomas of intermediate stiffness. Conclusions In this cohort, preoperative MRE predicted tumor consistency at the time of surgery. Tumor stiffness as measured using MRE outperformed conventional MRI because tumor appearance on T1- and T2-weighted images could only accurately predict the softest and hardest meningiomas.

To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women.Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE ε4 status in linear regression analysis.At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm(3) (95% confidence interval: -164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm(3) (95% confidence interval: -92.13, 599.4) at 48 months (p0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03).Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

The increasing prevalence of Alzheimer’s disease (AD) has provided motivation for developing novel methods for assessing the disease and the effects of potential treatments. Magnetic resonance elastography (MRE) is an MRI-based method for quantitatively imaging the shear tissue stiffness in vivo. The objective of this research was to determine whether this new imaging biomarker has potential for characterizing neurodegenerative disease. Methods were developed and tested for applying MRE to evaluate the mouse brain, using a conventional large bore 3.0T MRI system. The technique was then applied to study APP-PS1 mice, a well-characterized model of AD. Five APP-PS1 mice and 8 age-matched wild-type mice were imaged immediately following sacrifice. Brain shear stiffness measurements in APP-PS1 mice averaged 22.5% lower than those for wild-type mice (P = .0031). The results indicate that mouse brain MRE is feasible at 3.0T, and brain shear stiffness has merit for further investigation as a potential new biomarker for Alzheimer’s disease.

Purpose: To test patient acceptance and reproducibility of the 3D magnetic resonance elastography (MRE) brain exam using a soft vibration source, and to determine if MRE could noninvasively measure a change in the elastic properties of the brain parenchyma due to Alzheimer's disease (AD). Materials and Methods: MRE exams were performed using an accelerated spin-echo echo planar imaging (EPI) pulse sequence and stiffness was calculated with a 3D direct inversion algorithm. Reproducibility of the technique was assessed in 10 male volunteers, who each underwent four MRE exams separated into two imaging sessions. The effect of AD on brain stiffness was assessed in 28 volunteers, 7 with probable AD, 14 age- and gender-matched PIB-negative (Pittsburgh Compound B, a PET amyloid imaging ligand) cognitively normal controls (CN−), and 7 age- and gender-matched PIB-positive cognitively normal controls (CN+). Results: The median stiffness of the 10 volunteers was 3.07 kPa with a range of 0.40 kPa. The median and maximum coefficients of variation for these volunteers were 1.71% and 3.07%. The median stiffness of the 14 CN− subjects was 2.37 kPa (0.44 kPa range) compared to 2.32 kPa (0.49 kPa range) within the CN+ group and 2.20 kPa (0.33 kPa range) within the AD group. A significant difference was found between the three groups (P = 0.0055, Kruskal–Wallis one-way analysis of variance). Both the CN+ and CN− groups were significantly different from the AD group. Conclusion: 3D MRE of the brain can be performed reproducibly and demonstrates significantly reduced brain tissue stiffness in patients with AD. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.