UNASSIGNED: Diagnostic information about cell density variations and microscopic tissue anisotropy can be gained from tensor-valued diffusion magnetic resonance imaging (MRI). These properties of tissue microstructure have the potential to become novel imaging biomarkers for radiotherapy response. However, tensor-valued diffusion encoding is more demanding than conventional encoding, and its compatibility with MR scanners that are dedicated to radiotherapy has not been established. Thus, our aim was to investigate the feasibility of tensor-valued diffusion MRI with radiotherapy dedicated MR equipment.
UNASSIGNED: A tensor-valued diffusion protocol was implemented, and five healthy volunteers were scanned with different resolutions using conventional head coil and radiotherapy coil setup with fixation masks. Signal-to-noise-ratio (SNR) was evaluated to assess the risk of signal bias due to rectified noise floor. We also evaluated the repeatability and reproducibility of the microstructure parameters. One patient with brain metastasis was scanned to investigate the image quality and the transferability of the setup to diseased tissue.
UNASSIGNED: A resolution of 3 × 3 × 3 mm3 provided images with SNR > 3 for 93 % of the voxels using radiotherapy coil setup. The parameter maps and repeatability characteristics were comparable to those observed with a conventional head coil. The patient evaluation demonstrated successful parameter analysis also in tumor tissue, with SNR > 3 for 93 % of the voxels.
UNASSIGNED: We demonstrate that tensor-valued diffusion MRI is compatible with radiotherapy fixation masks and coil setup for investigations of microstructure parameters. The reported reproducibility may be used to plan future investigations of imaging biomarkers in brain cancer radiotherapy.

BACKGROUND: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.
METHODS: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.
RESULTS: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl\'s gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl\'s gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05).
CONCLUSIONS: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.
BACKGROUND: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.

Brain edema is a common feature associated with hepatic encephalopathy (HE). In patients with acute HE, brain edema has been shown to play a crucial role in the associated neurological deterioration. In chronic HE, advanced magnetic resonance imaging (MRI) techniques have demonstrated that low-grade brain edema appears also to be an important pathological feature. This review explores the different methods used to measure brain edema ex vivo and in vivo in animal models and in humans with chronic HE. In addition, an in-depth description of the main studies performed to date is provided. The role of brain edema in the neurological alterations linked to HE and whether HE and brain edema are the manifestations of the same pathophysiological mechanism or two different cerebral manifestations of brain dysfunction in liver disease are still under debate. In vivo MRI/magnetic resonance spectroscopy studies have allowed insight into the development of brain edema in chronic HE. However, additional in vivo longitudinal and multiparametric/multimodal studies are required (in humans and animal models) to elucidate the relationship between liver function, brain metabolic changes, cellular changes, cell swelling, and neurological manifestations in chronic HE.

Classification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification.
Anatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC).
The bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.570, p = 0.11). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.646 (p = 0.021). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.680, p = 0.005).
FTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.

Isolated adult-onset focal dystonia is considered a network disorder with disturbances to the motor basal ganglia and cerebellar circuits playing a pathophysiological role, but why specific body regions become affected remains unknown. We aimed to use diffusion tensor imaging to determine if the two most common phenotypes of focal dystonia are associated with distinguishing microstructural changes affecting the motor network.
Fifteen blepharospasm patients, 20 cervical dystonia patients, and 30 age- and sex-matched healthy controls were recruited. Maps of fractional anisotropy and mean diffusivity were analyzed using a voxel-based approach and an automated region-of-interest technique to evaluate deep gray matter nuclei. Correlations between diffusion measures and dystonia severity were tested, and post hoc discriminant analyses were conducted.
Voxel-based analyses revealed significantly reduced fractional anisotropy in the right cerebellum and increased mean diffusivity in the left caudate of cervical dystonia patients compared to controls, as well as lower fractional anisotropy in the right cerebellum in cervical dystonia patients relative to blepharospasm patients. In addition to reduced fractional anisotropy in the bilateral caudate nucleus of cervical dystonia patients relative to controls and blepharospasm patients, region-of-interest analyses revealed significantly reduced fractional anisotropy in the right globus pallidus internus and left red nucleus of blepharospasm patients compared to both controls and cervical dystonia patients. Diffusivity measures in the red nucleus of blepharospasm patients correlated with disease severity. In a three-group discriminant analysis, participants were correctly classified with only modest reliability (67-75%), but in a two-group discriminant analysis, patients could be distinguished from each other with high reliability (83-100%).
Different focal dystonia phenotypes are associated with distinct patterns of altered microstructure within constituent regions of basal ganglia and cerebellar circuits.

Previous studies reported that the volume of the left superior temporal gyrus (STG) is reduced in patients with schizophrenia and negatively correlated with hallucination severity. Moreover, diffusion-tensor imaging studies suggested a relationship between the brain microstructure in the STG of patients and auditory hallucinations. Hallucinations are also experienced in non-patient groups. This study investigated the relationship between hallucination proneness and the brain structure of the STG. Hallucination proneness was assessed by the Launey Slade Hallucination Scale (LSHS) in 25 healthy individuals who varied in their propensity to hear voices. Brain volume and microstructure of the STG was assessed by magnetic resonance imaging (MRI). Microstructure was examined by conventional diffusion-tensor imaging as well as by neurite orientation dispersion and density imaging (NODDI). The latter decomposes diffusion-based MRI into multiple compartments that characterize the brain microstructure by its neurite complexity known as orientation dispersion (ODI) and by its neurite density (NDI). Hallucination proneness was negatively correlated with the volume and microstructure (fractional anisotropy, neurite complexity) of the left but not the right STG. The strongest relationship (r = -0.563) was observed for neurite complexity (ODI). No correlation was observed for neurite density (NDI). These findings suggest that there is a relationship between the volume and the microstructure of the left STG and hallucination proneness. Dendritic complexity (but not neurite density) is inversely related to hallucination proneness. Metrics based on multi-compartment diffusion models seem to be more sensitive for hallucination-related neural processes than conventional MRI-based metrics.

Diffusion Tensor Imaging (DTI) can evaluate microstructural tissue damage in the optic radiation (OR) of patients with clinically isolated syndrome (CIS), early relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD). Different post-processing techniques, e.g. tract-based spatial statistics (TBSS) and probabilistic tractography, exist to quantify this damage.
To evaluate the capacity of TBSS-based atlas region-of-interest (ROI) combination with 1) posterior thalamic radiation ROIs from the Johns Hopkins University atlas (JHU-TBSS), 2) Juelich Probabilistic ROIs (JUEL-TBSS) and tractography methods using 3) ConTrack (CON-PROB) and 4) constrained spherical deconvolution tractography (CSD-PROB) to detect OR damage in patients with a) NMOSD with prior ON (NMOSD-ON), b) CIS and early RRMS patients with ON (CIS/RRMS-ON) and c) CIS and early RRMS patients without prior ON (CIS/RRMS-NON) against healthy controls (HCs).
Twenty-three NMOSD-ON, 18 CIS/RRMS-ON, 21 CIS/RRMS-NON, and 26 HCs underwent 3 T MRI. DTI data analysis was carried out using JUEL-TBSS, JHU-TBSS, CON-PROB and CSD-PROB. Optical coherence tomography (OCT) and visual acuity testing was performed in the majority of patients and HCs.
Absolute OR fractional anisotropy (FA) values differed between all methods but showed good correlation and agreement in Bland-Altman analysis. OR FA values between NMOSD and HC differed throughout the methodologies (p-values ranging from p < 0.0001 to 0.0043). ROC-analysis and effect size estimation revealed higher AUCs and R2 for CSD-PROB (AUC = 0.812; R2 = 0.282) and JHU-TBSS (AUC = 0.756; R2 = 0.262), compared to CON-PROB (AUC = 0.742; R2 = 0.179) and JUEL-TBSS (AUC = 0.719; R2 = 0.161). Differences between CIS/RRMS-NON and HC were only observable in CSD-PROB (AUC = 0.796; R2 = 0.094). No significant differences between CIS/RRMS-ON and HC were detected by any of the methods.
All DTI post-processing techniques facilitated the detection of OR damage in patient groups with severe microstructural OR degradation. The comparison of distinct disease groups by use of different methods may lead to different - either false-positive or false-negative - results. Since different DTI post-processing approaches seem to provide complementary information on OR damage, application of distinct methods may depend on the relevant research question.

Mutations in the progranulin (GRN) gene are a major source of inherited frontotemporal degeneration (FTD) spectrum disorders associated with TDP-43 proteinopathy. We use structural MRI to identify regions of baseline differences and longitudinal changes in gray matter (GM) and white matter (WM) in presymptomatic GRN mutation carriers (pGRN+) compared to young controls (yCTL).
Cognitively intact first-degree relatives of symptomatic GRN+ FTD patients with identified GRN mutations (pGRN+; N = 11, mean age = 41.4) and matched yCTL (N = 11, mean age = 53.6) were identified. They completed a MRI session with T1-weighted imaging to assess GM density (GMD) and diffusion-weighted imaging (DWI) to assess fractional anisotropy (FA). Participants completed a follow-up session with T1 and DWI imaging (pGRN+ mean interval 2.20 years; yCTL mean interval 3.27 years). Annualized changes of GMD and FA were also compared.
Relative to yCTL, pGRN+ individuals displayed reduced GMD at baseline in bilateral orbitofrontal, insular, and anterior temporal cortices. pGRN+ also showed greater annualized GMD changes than yCTL at follow-up in right orbitofrontal and left occipital cortices. We also observed reduced FA at baseline in bilateral superior longitudinal fasciculus, left corticospinal tract, and frontal corpus callosum in pGRN+ relative to yCTL, and pGRN+ displayed greater annualized longitudinal FA change in right superior longitudinal fasciculus and frontal corpus callosum.
Longitudinal MRI provides evidence of progressive GM and WM changes in pGRN+ participants relative to yCTL. Structural MRI illustrates the natural history of presymptomatic GRN carriers, and may provide an endpoint during disease-modifying treatment trials for pGRN+ individuals at risk for FTD.

SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan. Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration.

UNASSIGNED: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI.
UNASSIGNED: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT).
UNASSIGNED: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores.
UNASSIGNED: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.