Whole-brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism.

Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non-invasive mapping of human brain glucose metabolism following oral or intravenous administration of deuterium-labeled glucose. Regional differences in glucose metabolism can be observed in various brain pathologies, such as Alzheimer's disease, cancer, epilepsy or schizophrenia, but the achievable spatial resolution of conventional phase-encoded DMI methods is limited due to prolonged acquisition times rendering submilliliter isotropic spatial resolution for dynamic whole brain DMI not feasible. The purpose of this study was to implement non-Cartesian spatial-spectral sampling schemes for whole-brain 2H FID-MR Spectroscopic Imaging to assess time-resolved metabolic maps with sufficient spatial resolution to reliably detect metabolic differences between healthy gray and white matter regions. Results were compared with lower-resolution DMI maps, conventionally acquired within the same session. Six healthy volunteers (4 m/2 f) were scanned for ~90 min after administration of 0.8 g/kg oral [6,6']-2H glucose. Time-resolved whole brain 2H FID-DMI maps of glucose (Glc) and glutamate + glutamine (Glx) were acquired with 0.75 and 2 mL isotropic spatial resolution using density-weighted concentric ring trajectory (CRT) and conventional phase encoding (PE) readout, respectively, at 7 T. To minimize the effect of decreased signal-to-noise ratios associated with smaller voxels, low-rank denoising of the spatiotemporal data was performed during reconstruction. Sixty-three minutes after oral tracer uptake three-dimensional (3D) CRT-DMI maps featured 19% higher (p = .006) deuterium-labeled Glc concentrations in GM (1.98 ± 0.43 mM) compared with WM (1.66 ± 0.36 mM) dominated regions, across all volunteers. Similarly, 48% higher (p = .01) 2H-Glx concentrations were observed in GM (2.21 ± 0.44 mM) compared with WM (1.49 ± 0.20 mM). Low-resolution PE-DMI maps acquired 70 min after tracer uptake featured smaller regional differences between GM- and WM-dominated areas for 2H-Glc concentrations with 2.00 ± 0.35 mM and 1.71 ± 0.31 mM, respectively (+16%; p = .045), while no regional differences were observed for 2H-Glx concentrations. In this study, we successfully implemented 3D FID-MRSI with fast CRT encoding for dynamic whole-brain DMI at 7 T with 2.5-fold increased spatial resolution compared with conventional whole-brain phase encoded (PE) DMI to visualize regional metabolic differences. The faster metabolic activity represented by 48% higher Glx concentrations was observed in GM- compared with WM-dominated regions, which could not be reproduced using whole-brain DMI with the low spatial resolution protocol. Improved assessment of regional pathologic alterations using a fully non-invasive imaging method is of high clinical relevance and could push DMI one step toward clinical applications.

Assessment of Perivascular Space Morphometry Across the White Matter in Huntington's Disease Using MRI.

Background: Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington's disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies. Objective: To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined. Methods: White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured. Results: PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found. Conclusions: This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted.

TractGeoNet: A geometric deep learning framework for pointwise analysis of tract microstructure to predict language assessment performance.

We propose a geometric deep-learning-based framework, TractGeoNet, for performing regression using diffusion magnetic resonance imaging (dMRI) tractography and associated pointwise tissue microstructure measurements. By employing a point cloud representation, TractGeoNet can directly utilize tissue microstructure and positional information from all points within a fiber tract without the need to average or bin data along the streamline as traditionally required by dMRI tractometry methods. To improve regression performance, we propose a novel loss function, the Paired-Siamese Regression loss, which encourages the model to focus on accurately predicting the relative differences between regression label scores rather than just their absolute values. In addition, to gain insight into the brain regions that contribute most strongly to the prediction results, we propose a Critical Region Localization algorithm. This algorithm identifies highly predictive anatomical regions within the white matter fiber tracts for the regression task. We evaluate the effectiveness of the proposed method by predicting individual performance on two neuropsychological assessments of language using a dataset of 20 association white matter fiber tracts from 806 subjects from the Human Connectome Project Young Adult dataset. The results demonstrate superior prediction performance of TractGeoNet compared to several popular regression models that have been applied to predict individual cognitive performance based on neuroimaging features. Of the twenty tracts studied, we find that the left arcuate fasciculus tract is the most highly predictive of the two studied language performance assessments. Within each tract, we localize critical regions whose microstructure and point information are highly and consistently predictive of language performance across different subjects and across multiple independently trained models. These critical regions are widespread and distributed across both hemispheres and all cerebral lobes, including areas of the brain considered important for language function such as superior and anterior temporal regions, pars opercularis, and precentral gyrus. Overall, TractGeoNet demonstrates the potential of geometric deep learning to enhance the study of the brain's white matter fiber tracts and to relate their structure to human traits such as language performance.

Association Between Small Vessel Disease and Financial Capacity: A Study Based on Cognitively Normal Older Adults.

Background: Financial capacity is vital for the elderly, who possess a substantial share of global wealth but are vulnerable to financial fraud. Objective: We explored the link between small vessel disease (SVD) and financial capacity in cognitively unimpaired (CU) older adults via both cross-sectional and longitudinal analyses. Methods: 414 CU participants underwent MRI and completed the Financial Capacity Instrument-Short Form (FCI-SF). Subsequent longitudinal FCI-SF data were obtained from 104, 240, and 141 participants at one, two, and four years, respectively. SVD imaging markers, encompassing white matter hyperintensities (WMH), cerebral microbleeds (CMB), and lacune were evaluated. We used linear regression analyses to cross-sectionally explore the association between FCI-SF and SVD severity, and linear mixed models to assess how baseline SVD severity impacted longitudinal FCI-SF change. The false discovery rate method was used to adjust multiple comparisons. Results: Cross-sectional analysis revealed a significant association between baseline WMH and Bank Statement (BANK, ß=-0.194), as well as between lacune number and Financial Conceptual Knowledge (FC, ß= -0.171). These associations were stronger in APOE ɛ4 carriers, with ß= -0.282 for WMH and BANK, and ß= -0.366 for lacune number and FC. Longitudinally, higher baseline SVD total score was associated with severe FCI-SF total score decrease (ß= -0.335). Additionally, baseline WMH burden predicted future decreases in Single Checkbook/Register Task (SNG, ß= -0.137) and FC (ß= -0.052). Notably, the association between baseline WMH and SNG changes was amplified in APOE ɛ4 carriers (ß= -0.187). Conclusions: Severe SVD was associated with worse FCI-SF and could predict the decline of financial capacity in CU older adults.

Combined assessment of progressive apraxia of speech brain microstructure by diffusion tensor imaging tractography and multishell neurite orientation dispersion and density imaging.

BACKGROUND: Progressive apraxia of speech (PAOS) is characterized by difficulties with motor speech programming and planning. PAOS targets gray matter (GM) and white matter (WM) microstructure that can be assessed using diffusion tensor imaging (DTI) and multishell applications, such as neurite orientation dispersion and density imaging (NODDI). In this study, we aimed to apply DTI and NODDI to add further insight into PAOS tissue microstructure. METHODS: Twenty-two PAOS patients and 26 age- and sex-matched controls, recruited by the Neurodegenerative Research Group (NRG) at Mayo Clinic, underwent diffusion MRI on 3T MRI. Brain maps of fractional anisotropy (FA) and mean diffusivity (MD) from DTI and intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) from NODDI were generated. Global WM and GM, and specific WM tracts were identified using tractography and lobar GM regions. RESULTS: Global WM differences between PAOS and controls were greatest for ICVF, and global GM differences were greatest for MD and IsoVF. Abnormalities in key WM tracts involved in PAOS, including the body of the corpus callosum and frontal aslant tract, were identified with FA, MD, and ICVF, with excellent differentiation of PAOS from controls (area under the receiver operating characteristic curves >.90). MD and ICVF identified abnormalities in arcuate fasciculus, thalamic radiations, and corticostriatal tracts. Significant correlations were identified between an index of articulatory errors and DTI and NODDI metrics from the arcuate fasciculus, frontal aslant tract, and inferior longitudinal fasciculus. CONCLUSIONS: DTI and NODDI represent different aspects of brain tissue microstructure, increasing the number of potential biomarkers for PAOS.

Magnetic resonance fingerprinting-based myelin water fraction mapping for the assessment of white matter maturation and integrity in typical development and leukodystrophies.

A quantitative biomarker for myelination, such as myelin water fraction (MWF), would boost the understanding of normative and pathological neurodevelopment, improving patients' diagnosis and follow-up. We quantified the fraction of a rapidly relaxing pool identified as MW using multicomponent three-dimensional (3D) magnetic resonance fingerprinting (MRF) to evaluate white matter (WM) maturation in typically developing (TD) children and alterations in leukodystrophies (LDs). We acquired DTI and 3D MRF-based R1, R2 and MWF data of 15 TD children and 17 LD patients (9 months-12.5 years old) at 1.5 T. We computed normative maturation curves in corpus callosum and corona radiata and performed WM tract profile analysis, comparing MWF with R1, R2 and fractional anisotropy (FA). Normative maturation curves demonstrated a steep increase for all tissue parameters in the first 3 years of age, followed by slower growth for MWF while R1, R2R2 and FA reached a plateau. Unlike FA, MWF values were similar for regions of interest (ROIs) with different degrees of axonal packing, suggesting independence from fiber bundle macro-organization and higher myelin specificity. Tract profile analysis indicated a specific spatial pattern of myelination in the major fiber bundles, consistent across subjects. LD were better distinguished from TD by MWF rather than FA, showing reduced MWF with respect to age-matched controls in both ROI-based and tract analysis. In conclusion, MRF-based MWF provides myelin-specific WM maturation curves and is sensitive to alteration due to LDs, suggesting its potential as a biomarker for WM disorders. As MRF allows fast simultaneous acquisition of relaxometry and MWF, it can represent a valuable diagnostic tool to study and follow up developmental WM disorders in children.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

PURPOSE: To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. METHODS: Forty-four probable iNPH patients underwent 3 T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. RESULTS: In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). CONCLUSION: IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.

White matter integrity assessment in spinocerebellar ataxia type 2 (SCA2) patients.

AIM: To assess the burden of white matter (WM) damage in the cerebrum and cerebellum of spinocerebellar ataxia type 2 (SCA2) patients in an attempt to identify key regions affected by the neurodegenerative processes using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Nine SCA2 patients and 16 age-matched healthy controls were examined twice (SCA2 patients 3.6 ± 0.7 years and controls 3.3 ± 1.0 years apart) on the same 1.5 T scanner by acquiring T1-weighted and diffusion-weighted (b-value = 1,000 s/mm2) images. Using tract-based spatial statistics, DTI analysis on fractional anisotropy (FA), mean diffusivity (MD), axial (AD)/radial (RD) diffusivity was performed. RESULTS: At baseline magnetic resonance imaging (MRI), FA was significantly decreased in SCA2 patients in the corticospinal tracts, inferior and superior cerebellar peduncles, middle cerebellar peduncles, cerebral peduncles, right superior and posterior corona radiata. RD was only significantly increased in SCA2 patients in the middle cerebellar peduncles. No significant AD and MD changes were observed. Tract-based spatial statistics (TBSS) analysis between SCA2 patients at baseline and at follow-up showed no significant changes in any of the DTI metrics. CONCLUSIONS: DTI is a sensitive tool for following the progression of WM neurodegeneration and severity assessment in patients with SCA2. These findings add to a better understanding of the neurological underpinnings of the symptoms experienced by SCA2 patients.

Assessment of cheese sign and its association with vascular risk factors: Data from PUMCH dementia cohort.

BACKGROUND: In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors. METHODS: A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities. RESULTS: A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. CONCLUSIONS: The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Comprehensive assessment of sleep duration, insomnia, and brain structure within the UK Biobank cohort.

STUDY OBJECTIVES: To assess for associations between sleeping more than or less than recommended by the National Sleep Foundation (NSF), and self-reported insomnia, with brain structure. METHODS: Data from the UK Biobank cohort were analyzed (N between 9K and 32K, dependent on availability, aged 44 to 82 years). Sleep measures included self-reported adherence to NSF guidelines on sleep duration (sleeping between 7 and 9 hours per night), and self-reported difficulty falling or staying asleep (insomnia). Brain structural measures included global and regional cortical or subcortical morphometry (thickness, surface area, volume), global and tract-related white matter microstructure, brain age gap (difference between chronological age and age estimated from brain scan), and total volume of white matter lesions. RESULTS: Longer-than-recommended sleep duration was associated with lower overall grey and white matter volumes, lower global and regional cortical thickness and volume measures, higher brain age gap, higher volume of white matter lesions, higher mean diffusivity globally and in thalamic and association fibers, and lower volume of the hippocampus. Shorter-than-recommended sleep duration was related to higher global and cerebellar white matter volumes, lower global and regional cortical surface areas, and lower fractional anisotropy in projection fibers. Self-reported insomnia was associated with higher global gray and white matter volumes, and with higher volumes of the amygdala, hippocampus, and putamen. CONCLUSIONS: Sleeping longer than recommended by the NSF is associated with a wide range of differences in brain structure, potentially indicative of poorer brain health. Sleeping less than recommended is distinctly associated with lower cortical surface areas. Future studies should assess the potential mechanisms of these differences and investigate long sleep duration as a putative marker of brain health.

Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET.

OBJECTIVE: Multimodal imaging techniques have furthered our understanding of how different aspects of Alzheimer's disease (AD) pathology relate to one another. Diffusion tensor imaging (DTI) measures such as mean diffusivity (MD) may be a surrogate measure of the changes in gray matter structure associated with AD. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used to quantify synaptic loss, which is the major pathological correlate of cognitive impairment in AD. In this study, we investigated the relationship between gray matter microstructure and synaptic density. METHODS: DTI was used to measure MD and [11C]UCB-J PET to measure synaptic density in 33 amyloid-positive participants with AD and 17 amyloid-negative cognitively normal (CN) participants aged 50-83. Univariate regression analyses were used to assess the association between synaptic density and MD in both the AD and CN groups. RESULTS: Hippocampal MD was inversely associated with hippocampal synaptic density in participants with AD (r = -0.55, p <0.001, df = 31) but not CN (r = 0.13, p = 0.62, df = 15). Exploratory analyses across other regions known to be affected in AD suggested widespread inverse associations between synaptic density and MD in the AD group. CONCLUSION: In the setting of AD, an increase in gray matter MD is inversely associated with synaptic density. These co-occurring changes may suggest a link between synaptic loss and gray matter microstructural changes in AD. Imaging studies of gray matter microstructure and synaptic density may allow important insights into AD-related neuropathology.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

Racial and ethnic differences in the relationship between financial worry and white matter hyperintensities in Latinx, non-Latinx Black, and non-Latinx White older adults.

Socioeconomic status (SES) is associated with white matter hyperintensities (WMHs) and contributes to racial and ethnic health disparities. However, traditional measures of SES may not accurately represent individual financial circumstances among non-Latinx Black and Latinx older adults due to longstanding structural inequities. This study examined associations between multiple SES indicators (education, income, subjective financial worry) and WMHs across non-Latinx Black, Latinx, and non-Latinx White older adults in the Washington Heights-Inwood Columbia Aging Project (N = 662). Latinx participants reported the lowest SES and greatest financial worry, while Black participants evidenced the most WMHs. Greater financial worry was associated with higher WMHs volume above and beyond education and income, which were not associated with WMHs. However, this association was only evident among Latinx older adults. These results provide evidence for the minority poverty hypothesis and highlight the need for systemic socioeconomic interventions to alleviate brain health disparities in older adulthood.

Sex differences in white matter tracts of capuchin monkey brains.

Nonhuman primates exhibit sexual dimorphism in behavior, suggesting that there could be underlying differences in brain organization and function. Understanding this neuroanatomical variation is critical for enhancing our understanding of the evolution of sex differences in the human brain. Tufted capuchin monkeys (Sapajus [Cebus] apella) represent a phylogenetically diverse taxa of neotropical primates that converge on several behavioral characteristics with humans relevant to social organization, making them an important point of comparison for studying the evolution of sex differences in primates. While anatomical sex differences in gray matter have previously been found in capuchin monkeys, the current study investigates sex differences in white matter tracts. We carried out tract-based spatial statistical analysis on fractional anisotropy images of tufted capuchin monkeys (15 female, 5 male). We found that females showed significantly higher fractional anisotropy than males in regions of frontal-parietal white matter in the right cerebral hemisphere. Paralleling earlier findings in gray matter, male and female fractional anisotropy values in these regions were nonoverlapping. This complements prior work pointing toward capuchin sex differences in limbic circuitry and higher-order visual regions. We propose that these sex differences are related to the distinct socioecological niches occupied by male and female capuchins. Capuchin neuroanatomical sex differences appear to be more pronounced than in humans, which we suggest may relate to human adaptations for prolonged neurodevelopmental trajectories and increased plasticity.

Free-water correction DTI-based tractography in brain tumor surgery: assessment with functional and electrophysiological mapping of the white matter.

Peritumoral edema prevents fiber tracking from diffusion tensor imaging (DTI). A free-water correction may overcome this drawback, as illustrated in the case of a patient undergoing awake surgery for brain metastasis. The anatomical plausibility and accuracy of tractography with and without free-water correction were assessed with functional mapping and axono-cortical evoked-potentials (ACEPs) as reference methods. The results suggest a potential synergy between corrected DTI-based tractography and ACEPs to reliably identify and preserve white matter tracts during brain tumor surgery.

Assessment of the clinical feasibility of detecting subtle blood-brain barrier leakage in cerebral small vessel disease using dynamic susceptibility contrast MRI.

PURPOSE: Cerebral small vessel disease (cSVD) involves several pathologies affecting the small vessels, including blood-brain barrier (BBB) impairment. Dynamic susceptibility contrast (DSC) MRI is sensitive to both blood perfusion and BBB leakage, and correction methods may be crucial for obtaining reliable perfusion measures. These methods might also be applicable to detect BBB leakage itself. This study investigated to what extent DSC-MRI can measure subtle BBB leakage in a clinical feasibility setting. METHODS: In vivo DCE and DSC data were collected from fifteen cSVD patients (71 (±10) years, 6F/9M) and twelve elderly controls (71 (±10) years, 4F/8M). DSC-derived leakage fractions were obtained using the Boxerman-Schmainda-Weisskoff method (K2). K2 was compared with the DCE-derived leakage rate Ki, obtained from Patlak analysis. Subsequently, differences were assessed between white matter hyperintensities (WMH), cortical gray matter (CGM), and normal-appearing white matter (NAWM). Additionally, computer simulations were performed to assess the sensitivity of DSC-MRI to BBB leakage. RESULTS: K2 showed significant differences between tissue regions (P < 0.001 for CGM-NAWM and CGM-WMH, and P = 0.001 for NAWM-WMH). Conversely, according to the computer simulations the DSC sensitivity was insufficient to measure subtle BBB leakage, as the K2 values were below the derived limit of quantification (4∙10-3 min-1). As expected, Ki was elevated in the WMH compared to CGM and NAWM (P < 0.001). CONCLUSIONS: Although clinical DSC-MRI seems capable to detect subtle BBB leakage differences between WMH and normal-appearing brain tissue it is not recommended. K2 as a direct measure for subtle BBB leakage remains ambiguous as its signal effects are due to mixed T1- and T2∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects.

Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection.

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P < 0.001; MD [10-3 mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P < 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.