White Matter Regions Research Articles

Bilateral brain microstructural alterations in patients with left-sided classic trigeminal neuralgia: a diffusion kurtosis imaging study.

White matter microstructural abnormalities in patients with classic trigeminal neuralgia (TN) have been observed. However, the impact of classic TN in both hemispheres, the difference and extent of alterations in bilateral hemispheres, and the relationship between the impaired area and pain conduction are not fully understood. The purpose of this study was to investigate brain microstructural alterations and compare the bilateral hemispheres in patients with unilateral classic TN, as well as to explore their clinical implications. The authors performed a cross-sectional study of 36 patients with left classic TN (TN group; age 40-66 years) and 36 healthy controls (HC group; age 40-66 years). Diffusion kurtosis imaging (DKI; b-values = 0, 1250, and 2500 sec/mm2) was performed in all patients using a 3T MRI scanner. The FMRIB Software Library with tract-based spatial statistics was used to analyze intergroup differences in both hemispheres. Atlas-based region of interest analysis was conducted in fiber tracts and gray matter structures. Decreased fractional anisotropy (FA) and increased mean diffusivity in 2.70% and 5.34% of white matter regions, such as the corona radiata, corpus callosum, internal capsule, superior longitudinal fasciculus, and cingulum, were detected in the TN group compared with the HC group (p < 0.05, family-wise error correction). Reduced mean kurtosis (MK), axial kurtosis, and radial kurtosis were detected in the bilateral thalamus in TN patients. The FA and MK values decreased asymmetrically in both cerebral hemispheres. Atlas-based region of interest analysis revealed more pronounced FA and MK reductions in the left thalamus and posterior corona radiata. There were negative associations of disease duration and pain intensity with the MK values in the thalamus, internal capsule, and superior corona radiata. The authors concluded that unilateral TN could have asymmetrical microstructural alterations in bilateral hemispheres, which might be due to the compromised fiber tract integrity and abnormal neurons and synapses. The thalamus could be an important relay station in the pain conduction and modulation pathway and could have microstructural abnormalities in both the left and right sides. DKI could provide important information on the CNS pathophysiology of TN and assist in prognostic evaluation.

Positive Effects of Uric Acid on White Matter Microstructures and Treatment Response in Patients With Schizophrenia.

Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia. A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained. Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia. UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies.

Multi-modal morphometric association study of subclinical depressive symptoms using voxel-based morphometry, cortical thickness, and diffusion tensor imaging (DTI)

BackgroundCase-control studies in major depression have established numerous regional grey and white matter effects in fronto-limbic brain regions. Yet, brain structural studies of dimensional depressive psychopathology within the subclinical spectrum are still limited, in particular for multi-modal imaging approaches. MethodsUsing voxel-based and surface-based morphometry (cortical thickness) in combination with diffusion tensor imaging (DTI) in a large non-clinical sample (N = 300), we correlated grey and white matter structural variation with subclinical depressive symptoms assessed with Beck's Depression inventory (BDI). ResultsWe found a significant decrease of axial diffusivity associated with higher BDI scores in the left hippocampal part of the cingulum bundle (p < 0.05, threshold free cluster enhanced [TFCE] p-value) and some grey matter trend results e.g., a non-linear negative correlation of cortical thickness with depressive symptom load in the right pre/postcentral cortex (pFWE = 0.054, family wise error [FWE] peak level corrected) and a trend in grey matter volume decrease in women in the inferior frontal gyrus (pFWE = 0.054). LimitationsSince all grey matter effects disappear after FWE correction, we assume more stable effects in a larger, less homogenous sample enriched by help-seeking subjects covering a wider range of subclinical psychopathology. ConclusionOur study adds correlations between single depressive symptoms and brain structure to a growing literature. Since subclinical depression is increasingly recognised to be relevant in our understanding of manifest depression, early detection and identification of potential brain correlates of minor depressive symptoms has the potential to expand and reveal possible biomarkers and early psychological treatment.

Association between white matter hyperintensities and altered cerebral blood flow in maintenance hemodialysis patients: a longitudinal study

ObjectivesTo explore changes in cerebral blood flow (CBF) and white matter in hemodialysis patients.MethodsThirty-three hemodialysis patients who underwent two brain MRI at an interval of three years and 33 age- and sex-matched healthy controls (HC) underwent structural and arterial spin-labeling MRI examinations. Intergroup differences in CBF in the gray matter, white matter, and whole matter, and regional white matter hyperintensities (WMH) were analyzed. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups: an increased CBF group and a decreased CBF group. Differences in CBF and WMH between the subgroups and HC were analyzed.ResultsPatients undergoing hemodialysis exhibited increased cerebral watershed (CW) WMH, deep WMH, and periventricular WMH (P < 0.01). The CBF of patients with decreased CBF was higher than that of HC at baseline (,P < 0.01) and lower than that of HC at follow-up (P < 0.01). Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter (P < 0.01).ConclusionsWMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and CW, and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration.Advances in knowledgeThese findings provide a basis for exploring neuropathological changes of hemodialysis patients.

Multimodal imaging with magnetization transfer and diffusion tensor imaging reveals evidence of myelin damage in children and youth treated for a brain tumor.

The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI. Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial-spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI- fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls. MTR was decreased across multiple white matter tracts in patients when compared to healthy children, P < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, P < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, Ps < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, Ps < .01, but not healthy control children. Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.

Higher Regional Gray Matter Volume and White Matter Integrity in Individuals With Central Neuropathic Pain After Spinal Cord Injury.

Spinal cord injury (SCI) is a debilitating neurological condition that often leads to central neuropathic pain (CNP). As the fundamental mechanism of CNP is not fully established, its management is one of the most challenging problems among people with SCI. To shed more light on CNP mechanisms, the aim of this cross-sectional study was to compare the brain structure between individuals with SCI and CNP and those without CNP by examining the gray matter (GM) volume and the white matter (WM) integrity. Fifty-two individuals with SCI-28 with CNP and 24 without CNP-underwent a magnetic resonance imaging (MRI) session, including a T1-weighted scan for voxel-based morphometry, and a diffusion-weighted imaging (DWI) scan for WM integrity analysis, as measured by fractional anisotropy (FA) and mean diffusivity (MD). We found significantly higher GM volume in individuals with CNP compared with pain-free individuals in the right superior (p < 0.0014) and middle temporal gyri (p < 0.0001). Moreover, individuals with CNP exhibited higher WM integrity in the splenium of the corpus callosum (p < 0.0001) and in the posterior cingulum (p < 0.0001), compared with pain-free individuals. The results suggest that the existence of CNP following SCI is associated with GM and WM structural abnormalities in regions involved in pain intensification and spread, and which may reflect maladaptive neural plasticity in CNP.

Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status

BackgroundAPOE4 is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), whereas APOE2 confers protection. However, effects of APOE on neurodegeneration in cognitively intact individuals, and how these associations evolve with cognitive decline, are unclear. Furthermore, few studies have evaluated whether effects of APOE on neurodegenerative changes are modified by other AD key risk factors including age and sex.MethodsParticipants included older adults (57% women; 77 ± 7 years) from the Rancho Bernardo Study of Health Aging and the University of California San Diego Alzheimer’s Disease Research Center, including 192 cognitively normal (CN) individuals and 33 with mild cognitive impairment. Participants underwent diffusion MRI, and multicompartment restriction spectrum imaging (RSI) metrics were computed in white matter, gray matter, and subcortical regions of interest. Participants were classified as APOE4 carriers, APOE2 carriers, and APOE3 homozygotes. Analysis of covariance among CN (adjusting for age, sex, and scanner) assessed differences in brain microstructure by APOE, as well as interactions between APOE and sex. Analyses across all participants examined interactions between APOE4 and cognitive status. Linear regressions assessed APOE by age interactions.ResultsAmong CN, APOE4 carriers showed lower entorhinal cortex neurite density than non-carriers, whereas APOE2 carriers showed lower cingulum neurite density than non-carriers. Differences in entorhinal microstructure by APOE4 and in entorhinal and cingulum microstructure by APOE2 were present for women only. Age correlated with lower entorhinal restricted isotropic diffusion among APOE4 non-carriers, whereas age correlated with lower putamen restricted isotropic diffusion among APOE4 carriers. Differences in microstructure between cognitively normal and impaired participants were stronger for APOE4-carriers in medial temporal regions, thalamus, and global gray matter, but stronger for non-carriers in caudate.ConclusionsThe entorhinal cortex may be an early target of neurodegenerative changes associated with APOE4 in presymptomatic individuals, whereas APOE2 may support beneficial white matter and entorhinal microstructure, with potential sex differences that warrant further investigation. APOE modifies microstructural patterns associated with aging and cognitive impairment, which may advance the development of biomarkers to distinguish microstructural changes characteristic of normal brain aging, APOE-dependent pathways, and non-AD etiologies.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

IntroductionRegional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.Methods15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.ResultsCompared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges’ g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.ConclusionEOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

A pilot study of longitudinal changes in neurocognition, white matter hyperintensities, and cortical thickness in atrial fibrillation patients following catheter ablation vs medical management

BackgroundCerebral microembolization and atrophy complicate atrial fibrillation (AF). ObjectivesWe aimed to compare changes in neuroimaging findings between AF patients treated with catheter ablation and those treated with medical therapy. MethodsIn this pilot study, we evaluated differences in the change in regional white matter hyperintensity burden (WMHb) and cognitive function from baseline to 6-weeks and 1-year in patients treated with AF ablation (ABL, n=12) and patients treated with medical management alone (MM, n=11). Change in cortical thickness in Alzheimer’s Disease (AD)-risk, aging-associated or shared AD-risk/aging regions was also compared between groups. ResultsThe mean age was 69.7±5.0, 78% of patients were male, 39% had persistent AF, and all received oral anticoagulation. There were no significant differences between groups in the change in cognitive function. At 6-weeks, there were no significant differences in periventricular WMHb changes between groups (0.00 vs. 0.04; p=0.12), but changes in attention/concentration were inversely correlated with periventricular (p=0.01) and total WMHb (p=0.03). MM patients demonstrated significantly greater cortical thinning in AD-risk regions from baseline to 1-year (p=0.003). ConclusionsAF patients who underwent ablation demonstrated less cortical thinning in regions associated with AD risk than patients treated with medical therapy. Larger, prospective studies are needed to better understand the relationship between AF therapies and the development of cognitive decline.

The Association of Upper Airway Anatomy with Brain Structure: The Multi-Ethnic Study of Atherosclerosis.

Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities. Based in the Multi-Ethnic Study of Atherosclerosis, a longitudinal cohort study of community-dwelling adults, a comprehensive sleep study and an MRI of the upper airway and brain were performed on 578 participants. Machine learning models were used to select from 74 upper airway measures those measures most associated with selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between the selected upper airway measures, sleep measures, and brain structure. Maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and gray matter volume. Both coefficients were small (coefficients per standard deviation 0.063 mL, p = 0.04, and - 7.0 mL, p < 0.001 respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume (coefficient 0.164 mL, p = 0.007), and higher percentage of time in the N3 sleep stage was associated with larger total white and gray matter volume (4.8 mL, p = 0.004). Despite associations of two upper airway anatomy measures with brain volume, the evidence did not suggest that these upper airway and brain structure associations were acting primarily through the pathway of sleep disturbance.

Diffusion tensor imaging and plasma immunological biomarker panel in a rat traumatic brain injury (TBI) model and in human clinical TBI.

Neuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases. In the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury. 15 clinical TBI patients were similarly assessed for a panel of inflammatory markers and DTI post-intensive care unit discharge. Blood samples from healthy controls were used for comparison of the inflammatory markers. Time-dependent elevations in immunological markers were observed in TBI rats, with a correlation to preserved fractional anisotropy (FA) in white matter. Specifically, TBI-induced increased plasma levels of IL-1β, IL-6, G-CSF, CCL3, CCL5, and TNF-α were associated with higher white matter integrity, as measured by FA. Clinical cases had similar findings: elevated inflammatory markers (relative to controls) were associated with preservation of FA in vulnerable white matter regions. Inflammatory markers in post-TBI plasma samples are ambivalent with respect to prediction of favourable outcome versus a progression to more pervasive pathology and morbidity.

Levels of neuronal pentraxin 2 in plasma is associated with cognitive function in patients with schizophrenia.

The precise diagnosis and treatment of cognitive impairment remains a major challenge in the field of schizophrenia (SCZ) research. Synaptic dysfunction and loss are thought to be closely related to the occurrence and development of SCZ and may be involved in cognitive dysfunction. The purpose of this study was to investigate whether neuronal pentraxins (NPTXs) plays a role in the etiology of SCZ and provide evidence of its possible therapeutic value a new target for drug development. We recruited 275 participants, of whom 148 were SCZ from psychiatric hospital and 127 healthy control (HC) subjects from communities. Plasma concentrations of NPTXs were measured in HC and SCZ at baseline and after 8 weeks of antipsychotic treatment. The MATRICS Cognitive Consensus Battery was used to evaluate cognitive function. Furthermore, the brain is parcellated into 246 subregions using the Brainnetome atlas, and we extracted regional white matter volumes from magnetic resonance images of the SCZ groups. Plasma NPTX2 levels were significantly lower in SCZ compared with HC subjects, but were significantly raised in SCZ after 8 weeks of antipsychotic treatment compared to baseline. In addition, baseline plasma NPTX2 levels were positively correlated with cognitive performance. These findings indicate that NPTX2 may reveal novel aspects of disease etiology and act as a promising target for new drug development.

Old Age Exacerbates White Matter Neuroinflammation and Cognitive Deficits Following Closed-Head Injury, Particularly in Female Mice.

The increasing incidence of traumatic brain injury (TBI) among older adults, particularly mild injuries from falls, underscores the need to investigate age-related outcomes and potential sex differences in response to TBI. Although previous research has defined an aging-TBI signature (heightened glial responses and cognitive impairment) in open-skull moderate-to-severe TBI models, it is unknown whether this signature is also present in mild closed-head injuries (CHIs). This study explores the influences of age and sex on recovery in a mouse CHI model induced by an electromagnetic impactor device in 4-month-old and 18-month-old C57BL/6 mice. We assessed the righting reflex, body weight, behavior (radial arm water maze and active avoidance), and inflammation (GFAP, IBA1, CD45) in the neocortex, corpus callosum, and hippocampus. We observed that aged female mice exhibited more severe TBI-induced cognitive deficits. In addition, a more pronounced reactive neuroinflammatory response with age was noted within white matter regions. Conversely, gray matter regions in aged animals either showed no enhanced pathological changes in response to injury or the aged mice displayed hyporesponsive glia and signs of dystrophic glial degeneration that were not evident in their younger counterparts following CHI. These findings suggest that aging influences CHI outcomes, partially reflecting the aging-TBI signature seen in more severe injuries in white matter, while a distinct aging and mild-TBI signature was identified in gray matter. The heightened vulnerability of females to the combined effects of age and mild CHI establishes a foundation for further investigation into the mechanisms underlying the sexually dimorphic response in aging females.

White matter integrity in hospitalized COVID-19 patients is not associated with short- and long-term clinical outcomes.

SARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID. We included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (<3 months after positive PCR) and 3 months after baseline scanning. We assessed WM integrity using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) and performed comparisons between groups and within patients. Clinical assessment was conducted at 3 and 12 months with functional outcomes such as modified Rankin Scale (mRS), Post-COVID-19 Functional Status scale (PCFS), Visual Analogue Scale (VAS), and long COVID, cognitive assessment was conducted by the Modified Telephone Interview for Cognitive Status (TICS-M), and the Hospital Anxiety and Depression Scale (HADS) was used to assess mood disorder. Associations between WM integrity and clinical outcomes were evaluated using logistic regression and linear regression. A total of 49 patients (mean age 59.5 years) showed higher overall peak width of skeletonized mean diffusivity (PSMD) (p = 0.030) and lower neurite density index (NDI) in several WM regions compared with 25 controls at the baseline (p < 0.05; FWE-corrected) but did not remain statistically significant after adjusting for WM hyperintensities. Orientation dispersion index (ODI) increased after 3-month follow-up in several WM regions within patients (p < 0.05), which remained significant after correction for changes in WMH volume. Patients exhibited worse clinical outcomes compared with controls. Low NDI at baseline was associated with worse performance on the Post-COVID-19 Functional Status scale after 12 months (p = 0.018). After adjusting for WMH, hospitalized COVID-19 patients no longer exhibited lower WM integrity compared with controls. WM integrity was generally not associated with clinical assessments as measured shortly after discharge, suggesting that factors other than underlying WM integrity play a role in worse clinical outcomes or long COVID.

Transcranial blood-brain barrier opening in Alzheimer's disease patients using a portable focused ultrasound system with real-time 2-D cavitation mapping.

Background : Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer's disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting its widespread clinical adoption. In this pilot study, we investigate the clinical safety and feasibility of a portable, non-invasive neuronavigation-guided FUS (NgFUS) system with integrated real-time 2-D microbubble cavitation mapping. Methods : A phase 1 clinical study with mild to moderate AD patients (N = 6) underwent a single session of microbubble-mediated NgFUS to induce transient BBB opening (BBBO). Microbubble activity under FUS was monitored with real-time 2-D cavitation maps and dosing to ensure the efficacy and safety of the NgFUS treatment. Post-operative MRI was used for BBB opening and closure confirmation as well as safety assessment. Changes in AD biomarker levels in both blood serum and extracellular vesicles (EVs) were evaluated, while changes in amyloid-beta (Aβ) load in the brain were assessed through 18F-florbetapir PET. Results : BBBO was achieved in 5 out of 6 subjects with an average volume of 983 ± 626 mm3 following FUS at the right frontal lobe both in white and gray matter regions. The outpatient treatment was completed within 34.8 ± 10.7 min. Cavitation dose significantly correlated with the BBBO volume (R 2 > 0.9, N = 4), demonstrating the portable NgFUS system's capability of predicting opening volumes. The cavitation maps co-localized closely with the BBBO location, representing the first report of real-time transcranial 2-D cavitation mapping in the human brain. Larger opening volumes correlated with increased levels of AD biomarkers, including Aβ42 (R 2 = 0.74), Tau (R 2 = 0.95), and P-Tau181 (R 2 = 0.86), assayed in serum-derived EVs sampled 3 days after FUS (N = 5). From PET scans, subjects showed a lower Aβ load increase in the treated frontal lobe region compared to the contralateral region. Reduction in asymmetry standardized uptake value ratios (SUVR) correlated with the cavitation dose (R 2 > 0.9, N = 3). Clinical changes in the mini-mental state examination over 6 months were within the expected range of cognitive decline with no additional changes observed as a result of FUS. Conclusion : We showed the safety and feasibility of this cost-effective and time-efficient portable NgFUS treatment for BBBO in AD patients with the first demonstration of real-time 2-D cavitation mapping. The cavitation dose correlated with BBBO volume, a slowed increase in pathology, and serum detection of AD proteins. Our study highlights the potential for accessible FUS treatment in AD, with or without drug delivery.

Evidence for inflammation in normal-appearing brain regions in patients with growing sporadic vestibular schwannoma: A PET study.

Nonauditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these symptoms is unknown. Inflammation is hypothesized to play a key role in the growth and symptomatic presentation of sporadic VS, and in this study, we investigated through translocator protein (TSPO) positron emission tomography (PET) whether inflammation occurred within the "normal appearing" brain of such patients and its association with tumor growth. Dynamic PET datasets from 15 patients with sporadic VS (8 static and 7 growing) who had been previously imaged using the TSPO tracer [11C](R)-PK11195 were included. Parametric images of [11C](R)-PK11195 binding potential (BPND) and the distribution volume ratio (DVR) were derived and compared across VS growth groups within both contralateral and ipsilateral gray (GM) and white matter (WM) regions. Voxel-wise cluster analysis was additionally performed to identify anatomical regions of increased [11C](R)-PK11195 binding. Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, P = .03) and whole brain (GM & WM, 1.045 vs. 1.006, P = .03) [11C](R)-PK11195 DVR values. The voxel-wise analysis supported the region-based analysis and revealed clusters of high TSPO binding within the precentral, postcentral, and prefrontal cortex in patients with growing VS. We present the first in vivo evidence of increased TSPO expression and inflammation within the brains of patients with growing sporadic VS. These results provide a potential mechanistic insight into the development of nonauditory symptoms in these patients and highlight the need for further studies interrogating the role of neuroinflammation in driving VS symptomatology.

Feasibility study of dual-accelerated simultaneous multi-slice imaging in diffusion tensor imaging of glioma.

To explore the value of dual-accelerated simultaneous multi-slice (SMS) imaging in diffusion tensor imaging (DTI) of glioma. Thirty-four patients with glioma who underwent magnetic resonance imaging (MRI) in our hospital from January 2022 to March 2023 were randomly selected. The results of dual-accelerated SMS-DTI and conventional DTI were retrospectively analyzed. All patients were scanned using a uMR790 3.0T MRI scanner, and the scanning technicians followed a predefined sequence to ensure consistency in scan parameters. The images were subjectively evaluated using a Likert 5-point scoring system. Objective evaluation was performed by measuring the required values of the images with b-value = 1000 s/mm2, primarily measuring the signal intensity in the tumor region and the contralateral normal brain white matter region. The standard deviation values were used to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the same encoding direction as the background noise. The number of generated fiber pathways, fractional anisotropy (FA), and mean diffusivity (MD) were measured and analyzed using post-processing software. The relative FA (rFA) and relative MD (rMD) were calculated. The results of conventional DTI and SMS-accelerated DTI were compared. In terms of subjective evaluation, including overall image quality, tumor edge clarity, and magnetic sensitivity artifacts, both techniques showed no significant differences, indicating comparable diagnostic performance in anatomical visualization. In terms of objective evaluation and quantitative parameter measurement, there were statistically significant differences in SNR and CNR values, with slightly lower values in the dual-accelerated SMS-DTI compared with conventional DTI, a significant reduction in scanning time can be achieved through a slight loss in image quality. The number of fiber pathways and the rFA and rMD values did not show typical differences between the two techniques. The correlation between these measures was highly similar, with no significant differences observed. The application of dual-accelerated simultaneous multi-slice imaging in DTI of glioma is feasible.

Age-Related Decline in Brain Myelination: Quantitative Macromolecular Proton Fraction Mapping, T2-FLAIR Hyperintensity Volume, and Anti-Myelin Antibodies Seven Years Apart.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33-60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Effects of multiple anesthetic exposures on rhesus macaque brain development: a longitudinal structural MRI analysis.

Concerns about the potential neurotoxic effects of anesthetics on developing brain exist. When making clinical decisions, the timing and dosage of anesthetic exposure are critical factors to consider due to their associated risks. In our study, we investigated the impact of repeated anesthetic exposures on the brain development trajectory of a cohort of rhesus monkeys (n = 26) over their first 2yr of life, utilizing longitudinal magnetic resonance imaging data. We hypothesized that early or high-dose anesthesia exposure could negatively influence structural brain development. By employing the generalized additive mixed model, we traced the longitudinal trajectories of brain volume, cortical thickness, and white matter integrity. The interaction analysis revealed that age and cumulative anesthetic dose were variably linked to white matter integrity but not to morphometric measures. Early high-dose exposure was associated with increased mean, axial, and radial diffusivities across all white matter regions, compared to late-low-dose exposure. Our findings indicate that early or high-dose anesthesia exposure during infancy disrupts structural brain development in rhesus monkeys. Consequently, the timing of elective surgeries and procedures that require anesthesia for children and pregnant women should be strategically planned to account for the cumulative dose of volatile anesthetics, aiming to minimize the potential risks to brain development.

Quantitative brain morphometry identifies cerebellar, cortical, and subcortical gray and white matter atrophy in late-onset Tay-Sachs disease.

Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.