High-resolution Magnetic Resonance Imaging Research Articles

The Douglas-Bell Canada Brain Bank Post-mortem Brain Imaging Protocol

Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Post-mortem MRIs can provide complementary anatomical and microstructural information to in vivo imaging and ex vivo neuropathological assessments without compromising the sample for future investigations. We have developed a post-mortem MRI protocol for the brain specimens of the Douglas-Bell Canada Brain Bank (DBCBB), the largest brain bank in Canada housing over 3000 neurotypical and diseased brain specimens, that allows for acquisition of high-resolution 3T and 7T MRIs. Our protocol can be used to scan DBCBB specimens with minimal tissue manipulation, allowing for feasibly scanning large numbers of post-mortem specimens while retaining the quality of the tissue for downstream histology and immunohistochemistry assessments. We demonstrate the robustness of this protocol despite the dependency of image quality on fixation by acquiring data on the first day of extraction and fixation, to over twenty years post fixation. The acquired images can be used to perform volumetric segmentations, cortical thickness measurements, and quantitative analyses which can be potentially used to link MRI-derived and ex vivo histological measures, assaying both the normative organization of the brain and ex vivo measures of pathology.

Senolytic therapy preserves blood-brain barrier integrity and promotes microglia homeostasis in a tauopathy model

Cellular senescence, characterized by expressing the cell cycle inhibitory proteins, is evident in driving age-related diseases. Senescent cells play a crucial role in the initiation and progression of tau-mediated pathology, suggesting that targeting cell senescence offers a therapeutic potential for treating tauopathy associated diseases. This study focuses on identifying non-invasive biomarkers and validating their responses to a well-characterized senolytic therapy combining dasatinib and quercetin (D + Q), in a widely used tauopathy mouse model, PS19. We employed human-translatable MRI measures, including water extraction with phase-contrast arterial spin tagging (WEPCAST) MRI, T2 relaxation under spin tagging (TRUST), longitudinally assessed brain physiology and high-resolution structural MRI evaluated the brain regional volumes in PS19 mice. Our data reveal increased BBB permeability, decreased oxygen extraction fraction, and brain atrophy in 9-month-old PS19 mice compared to their littermate controls. (D + Q) treatment effectively preserves BBB integrity, rescues cerebral oxygen hypometabolism, attenuates brain atrophy, and alleviates tau hyperphosphorylation in PS19 mice. Mechanistically, D + Q treatment induces a shift of microglia from a disease-associated to a homeostatic state, reducing a senescence-like microglial phenotype marked by increased p16/Ink4a. D + Q-treated PS19 mice exhibit enhanced cue-associated cognitive performance in the tracing fear conditioning test compared to the vehicle-treated littermates, implying improved cognitive function by D + Q treatment. Our results pave the way for application of senolytic treatment as well as these noninvasive MRI biomarkers in clinical trials in tauopathy associated neurological disorders.

Machine learning localization to identify the epileptogenic side in mesial temporal lobe epilepsy

BackgroundMesial temporal sclerosis (MTS) is the most common pathology associated with drug-resistant mesial temporal lobe epilepsy (mTLE) in adults.Most atrophic hippocampi can be identified using MRI based on standard epilepsy protocols; however, difficulties can arise in cases where sclerotic changes in the hippocampus are subtle or non-epilepsy-specific protocols have been implemented. In such cases, quantitative methods, such as T1-weighted axial series MRIs, are valuable additional tools to complement epilepsy-specific protocols. In the current study, we applied machine learning (ML) techniques to the analysis of brain regions of interest (ROIs), including the hippocampus, thalamus, and cortical areas, to enhance the accuracy of lesion lateralization in MRI. MethodsThis study included 104 patients diagnosed with mTLE, including 55 with lesions on the right side and 49 with lesions on the left side. FreeSurfer software was used to extract features from high-resolution T1-weighted axial brain MRI scans for use in computing lateralization indices (LI) for various brain regions. After using feature selection to pinpoint critical ROIs, the corresponding LI values were used as parameters in training the ML model. ResultsThe proposed ML model demonstrated exceptional performance in the lateralization of mTLE, achieving test accuracy of 92.38 % with an AUROC of 0.97. ConclusionThis study demonstrated the efficacy of ML in detecting instances of MTS from thin-slice T1 images. The proposed method provides valuable insights for surgical planning and treatment. Nonetheless, additional research will be required to enhance the robustness of the model and rigorously validate its effectiveness and applicability in clinical settings.

Computational modeling of predicting cerebrovascular injury in traumatic brain injury patients

Despite significant progress in understanding traumatic brain injury (TBI) and subsequent outcomes, predicting and preventing cerebrovascular injury (CVI) remains challenging. We introduces a novel computational modeling approach using advanced fluid-structure interaction (FSI) models, which incorporate high-resolution magnetic resonance imaging (MRI) data to analyze changes in intracranial pressure and blood flow in cerebral arteries post-TBI. We analyzed the mechanical fields between the PCOMA, ICA, PCA, and ACA areas by conducting a region of interest analysis in this research. The approach uniquely integrates detailed patient-specific brain vasculature geometries and dynamic boundary conditions to enhance predictive accuracy. The model indicates that peak pressure in the anterior cerebral artery (ACA) reaches 130 kPa within the first hour post-injury, with a 20% increase observed at 2 milliseconds. Wall shear stress (WSS) in the posterior communicating artery (PCOMA) reaches 140 kPa, which exceeds the typical physiological range of 10–20 kPa and may lead to endothelial damage. Regions such as the PCOMA and ACA are identified as particularly vulnerable to high mechanical stress and strain, which suggests the need for timely medical intervention to reduce the risk of CVI. Further validation with clinical data is required to improve the predictive accuracy of the model.

Morphological analysis of the trigeminal nerve in trigeminal neuralgia using the nerve's centerline and multiple cross-sections of a 3D model.

Morphological changes such as angulation and torsion of the trigeminal nerve have been reported to cause trigeminal neuralgia (TN). The authors sought to quantify and objectively evaluate the morphological changes of the trigeminal nerve and to elucidate the cause of TN. The authors retrospectively analyzed the cases of patients with primary TN who had undergone microvascular decompression at a single facility between January 2016 and December 2022 and had both single-artery compression and a good postoperative outcome. The authors performed segmentation of the trigeminal nerve by using the patients' pre- and postoperative high-resolution MR images, and they then created a 3D model. The centerline of the trigeminal nerve was obtained using volume skeletonization, and the authors created multiple cross-sectional images by reslicing the 3D model perpendicular to the centerline. The parameters analyzed were as follows: the 1) centerline length; 2) centerline curvature; 3) centerline torsion; 4) cross-sectional area; 5) cross-sectional flattening ratio; and 6) cross-sectional long-axis angle. Comparisons were made for each parameter between the affected and unaffected side and between preoperative and postoperative trigeminal nerve findings. After exclusions, 70 of the 127 patients who underwent microvascular decompression during the study period were included in the analysis. In the preoperative images, the trigeminal nerve on the affected side had a significantly longer centerline length (p = 0.0003), greater curvature (p = 0.0012), smaller cross-sectional area (p < 0.0001), and greater flattening ratio (p = 0.0059) than the unaffected side. On the affected side, the preoperative trigeminal nerve had a significantly longer centerline length (p < 0.0001), greater curvature (p = 0.0028), and smaller cross-sectional area (p < 0.0001) compared to the postoperative trigeminal nerve. It is possible to analyze the morphological changes of the trigeminal nerve by using this method. In the preoperative trigeminal nerve on the affected side, the centerline is long and curved, and the cross-sectional area is small and flat. Further analyses may help clarify the pathophysiology, aid in diagnoses, and predict the efficacy of treatment.

Hybrid Somatostatin Receptor PET/MRI of the Head and Neck.

Hybrid PET/MRI has the potential to transform neuro-oncologic imaging, particularly in diagnosis and treatment planning of somatostatin receptor-expressing tumors of the head and neck. Hybrid PET/MRI combines high-resolution MRI with functional information from PET, providing precise anatomic information and overcoming difficulties in localization inherent to PET alone. There is a range of tumors in the head and neck that overexpress somatostatin receptors and are therefore amenable to evaluation with somatostatin receptor PET/MRI. These include meningiomas, paragangliomas, olfactory neuroblastomas, pituitary neuroendocrine tumors, middle ear neuroendocrine tumors, and medullary thyroid carcinomas. The combination of PET and MRI is superior to either modality alone and can address several unique diagnostic challenges associated with these lesions. The authors discuss the superior capabilities of somatostatin receptor PET/MRI, including improved lesion localization, more sensitive demonstration of disease extent, enhanced surveillance, optimized radiation therapy planning, and accurate prediction of response to somatostatin analog therapy. Although there are only a few dedicated PET/MRI units available in clinical practice, commercial software is now available that can automatically fuse PET/CT data with recently acquired MRI data, increasing the availability of this approach. Radiologists should be aware of the advantages of somatostatin receptor PET/MRI in evaluation of head and neck tumors as well as the potential pitfalls of this approach so that they can accurately advise clinicians and better interpret these studies. ©RSNA, 2024 See the invited commentary by Shatzkes and Strauss in this issue.

White matter spinal tracts impairment in patients with degenerative cervical myelopathy evaluated with the magnetization transfer saturation MRI technique.

Prospective case-control study. We investigated the use of the magnetization transfer saturation (MTsat) technique to assess the structural integrity of the spinal cord tracts in individuals with clinically significant degenerative cervical myelopathy (DCM) and associated disability. Novosibirsk Neurosurgery Centre, Russia. A total of 53 individuals diagnosed with DCM and 41 patients with cervical radiculopathy underwent high-resolution MRI of the cervical spinal cord via the magnetization transfer technique. The MRI data were processed using the Spinal Cord Toolbox (v5.5), with MTsat values determined for each spinal tract and compared between the two groups. Furthermore, associations between MTsat values and the clinical disability rates of patients were investigated. A significant decrease in the MTsat of the ventral spinocerebellar tract was observed in the DCM group compared to the control group (adjusted p < 0.001). There was a trend towards lower MTsat values in the rubrospinal tract in the DCM group (adjusted p = 0.08). Additionally, a decrease in MTsat values in the lateral funiculi of the spinal cord was found in patients with DCM (adjusted p < 0.01). Furthermore, a trend toward a positive correlation was observed between the JOA score and the MTsat values within the ventral spinocerebellar tract (R = 0.33, adjusted p = 0.051). The findings of our study indicate that demyelination in patients with DCM affects mainly the ventral spinocerebellar and rubrospinal tracts, and the extent of changes in the ventral spinocerebellar tract is related to the severity of the condition.

Vessel wall MRI in giant cell arteritis: standardized protocol and scoring approach developed by an international working group.

There are an increasing number of centers performing research on high-resolution vessel wall magnetic resonance imaging (VW-MRI) in giant cell arteritis (GCA). However, harmonized approaches to VW-MRI in GCA are lacking and are essential to performing multicentre studies. Using a data-driven, consensus-based approach, an international expert group developed a standardized MRI protocol and scoring system to advance multi-centered research in cranial GCA. A targeted literature review of VW-MRI in cranial GCA was conducted. A working group comprised of radiologists, rheumatologists, and ophthalmologists with expertise in VW-MRI and GCA reviewed the results of the literature search, presented relevant data and images from their respective centers, and then reached consensus on recommendations related to key MRI structures, MRI sequences, scoring system, and other important considerations. A total of 21 relevant articles were identified and reviewed. Based on published literature, structures to be evaluated on MRI were categorized based on anatomic location (extradural cranial, intradural cranial, and orbits) and prioritization (core vs elective). Essential and elective sequences to comprehensively image cranial and orbital structures while minimizing scan time were determined along with scoring systems to grade contrast enhancement. This report describes a standardized approach to facilitate research of VW-MRI in cranial GCA that is the result of a multi-disciplinary, international collaboration of experts in VW-MRI and/or GCA.

There is poor agreement between the subjective and quantitative adjudication of aneurysm wall enhancement.

The determination of Aneurysm wall enhancement (AWE) by human readers on visual inspection alone is subjective and prone to error. A three-dimensional (3D) method for quantifying the aneurysm wall's signal intensity (SI) enables objective determination of AWE. Inter-reader agreement and agreement between subjective and objective determination of AWE were assessed in this study. Patients with saccular intracranial aneurysms (IAs) were imaged with high-resolution MRI. Subjective assessment: Two internal adjudicators visually determined AWE if the degree of enhancement was equal to or higher than the pituitary stalk. An experienced internal neuroradiologist resolved disagreements. This internal adjudication was compared with an external adjudication to assess inter-rater agreement among centers. Objective assessment: The distribution of SI across the aneurysm wall after normalizing the SI to the corpus callosum was determined with an in-house code. The normalized mean SI on post-contrast T1 MRI was defined as 3D-circumferential AWE (3D-CAWE). If the 3D-CAWE value was higher than one, an IA was defined as objectively "enhancing." Inter-rater agreement was analyzed with kappa coefficients. Inter-technique agreement between subjective and objective assessment was performed using kappa statistics. Univariate regressions were performed to identify which morphological characteristics influenced subjective adjudication of enhancement. A total of 113 IAs were analyzed. The agreement of the internal assessment was moderate (k = 0.63), 49.5% of IAs (56) were classified as "enhancing" and 50.5% (57) as "non-enhancing" after consensus. Inter-rater agreement between internal and external adjudication was weak (k = 0.52) for the presence of AWE. There was no agreement between the subjective assessment of AWE and objective 3D-CAWE (k = 0.16, p 0.02). Subjective assessment was less likely to reliably adjudicate enhancement when assessing multiple aneurysms (OR 0.4, 95% CI 0.16 -0.97, p 0.04) and IAs larger than > 7 mm (OR 0.22, 95% CI 0.09 -0.55, p 0.002) despite being objectively "non-enhancing". Subjective adjudication of AWE has poor inter-rater agreement, and no agreement with an objective 3D method of determining AWE. It is also less likely than objective quantification to identify enhancement in aneurysms larger than 7 mm or when multiple aneurysms are present. Objective 3D quantification, such as the technique used in this study, should therefore be considered when assessing AWE, especially in patients with multiple aneurysms and aneurysms larger than 7 mm in size. 3D, three-dimensional; 3D-CAWE, three-dimensional circumferential aneurysm wall enhancement; AWE, aneurysm wall enhancement; Gd, gadolinium; HR-MRI, high resolution MRI; HR 3D T1 VWI, high-resolution 3D T1 weighted black blood vessel wall imaging; IA, intracranial aneurysm; SI, signal intensity.

Radiomic detection of abnormal brain regions in tuberous sclerosis complex.

Radiomics refers to the extraction of quantitative information from medical images and is most commonly utilized in oncology to provide ancillary information for solid tumor diagnosis, prognosis, and treatment response. The traditional radiomic pipeline involves segmentation of volumes of interest with comparison to normal brain. In other neurologic disorders, such as epilepsy, lesion delineation may be difficult or impossible due to poor anatomic definition, small size, and multifocal or diffuse distribution. Tuberous sclerosis complex (TSC) is a rare genetic disease in which brain magnetic resonance imaging (MRI) demonstrates multifocal abnormalities with variable imaging and epileptogenic features. The purpose of this study was to develop a radiomic workflow for identification of abnormal brain regions in TSC, using a whole-brain atlas-based approach with generation of heatmaps based on signal deviation from normal controls. This was a retrospective pilot study utilizing high-resolution whole-brain 3D FLAIR MRI datasets from retrospective enrollment of tuberous sclerosis complex (TSC) patients and normal controls. Subjects underwent MRI including high-resolution 3D FLAIR sequences. Preprocessing included skull stripping, coregistration, and intensity normalization. Using the Brainnetome and Harvard-Oxford atlases, brain regions were parcellated into 318 discrete regions. Expert neuroradiologists spatially labeled all tubers in TSC patients using ITK-SNAP. The pyradiomics toolbox was used to extract 88 radiomic features based on IBSI guidelines, comparing tuber-affected and non-tuber-affected parenchyma in TSC patients, as well as normal brain tissue in control patients. For model training and validation, regions with tubers from 20 TSC patients and 30 normal control subjects were randomly divided into two training sets (80%) and two validation sets (20%). Additional model testing was performed on a separate group of 20 healthy controls. LASSO (least absolute shrinkage and selection operator) was used to perform variable selection and regularization to identify regions containing tubers. Relevant radiomic features selected by LASSO were combined to produce a radiomic score ω, defined as the sum of squared differences from average control group values. Region-specific ω scores were converted to heat maps and spatially coregistered with brain MRI to reflect overall radiomic deviation from normal. The proposed radiomic workflow allows for quantification of deviation from normal in 318 regions of the brain with the use of a summative radiomic score ω. This score can be used to generate spatially registered heatmaps to identify brain regions with radiomic abnormalities. The pilot study of TSC showed radiomic scores ω that were statistically different in regions containing tubers from regions without tubers/normal brain (p<0.0001). Our model exhibits an AUC of 0.81 (95% confidence interval: 0.78-0.84) on the testing set, and the best threshold obtained on the training set, when applied to the testing set, allows us to identify regions with tubers with a specificity of 0.91 and a sensitivity of 0.60. We describe a whole-brain atlas-based radiomic approach to identify abnormal brain regions in TSC patients. This approach may be helpful for identifying specific regions of interest based on relatively greater signal deviation, particularly in clinical scenarios with numerous or poorly defined anatomic lesions.

Radiomic profiling of high-risk aneurysms with blebs: an exploratory study

BackgroundBlebs significantly increase rupture risk of intracranial aneurysms. Radiomic analysis offers a robust characterization of the aneurysm wall. However, the unique radiomic profile of various compartments, including blebs, remains unexplored....

Morphometry of medial temporal lobe subregions using high-resolution T2-weighted MRI in ADNI3: Why, how, and what's next?

This paper for the 20th anniversary of the Alzheimer's Disease Neuroimaging Initiative (ADNI) provides an overview of magnetic resonance imaging (MRI) of medial temporal lobe (MTL) subregions in ADNI using a dedicated high-resolution T2-weighted sequence. A review of the work that supported the inclusion of this imaging modality into ADNI Phase 3 is followed by a brief description of the ADNI MTL imaging and analysis protocols and a summary of studies that have used these data. This review is supplemented by a new study that uses novel surface-based tools to characterize MTL neurodegeneration across biomarker-defined AD stages. This analysis reveals a pattern of spreading cortical thinning associated with increasing levels of tau pathology in the presence of elevated amyloid beta, with apparent epicenters in the transentorhinal region and inferior hippocampal subfields. The paper concludes with an outlook for high-resolution imaging of the MTL in ADNI Phase 4. HIGHLIGHTS: As of Phase 3, the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) protocol includes a high-resolution T2-weighted MRI scan optimized for imaging hippocampal subfields and medial temporal lobe (MTL) subregions. These scans are processed by the ADNI core to obtain automatic segmentations of MTL subregions and to derive morphologic measurements. More detailed granular examination of MTL neurodegeneration in response to disease progression is achieved by applying surface-based modeling techniques. Surface-based analysis of gray matter loss in MTL subregions reveals increasing and spatially expanding patterns of neurodegeneration with advancing stages of Alzheimer's disease (AD), as defined based on amyloid and tau positron emission tomography biomarkers in accordance with recently proposed criteria. These patterns closely align with post mortem literature on spread of pathological tau in AD, supporting the role of tau pathology in the presence of elevated levels of amyloid beta as the driver of neurodegeneration.

A novel GAN-based three-axis mutually supervised super-resolution reconstruction method for rectal cancer MR image

Background and objectiveThis study aims to enhance the resolution in the axial direction of rectal cancer magnetic resonance (MR) imaging scans to improve the accuracy of visual interpretation and quantitative analysis. MR imaging is a critical technique for the diagnosis and treatment planning of rectal cancer. However, obtaining high-resolution MR images is both time-consuming and costly. As a result, many hospitals store only a limited number of slices, often leading to low-resolution MR images, particularly in the axial plane. Given the importance of image resolution in accurate assessment, these low-resolution images frequently lack the necessary detail, posing substantial challenges for both human experts and computer-aided diagnostic systems. Image super-resolution (SR), a technique developed to enhance image resolution, was originally applied to natural images. Its success has since led to its application in various other tasks, especially in the reconstruction of low-resolution MR images. However, most existing SR methods fail to account for all anatomical planes during reconstruction, leading to unsatisfactory results when applied to rectal cancer MR images. MethodsIn this paper, we propose a GAN-based three-axis mutually supervised super-resolution reconstruction method tailored for low-resolution rectal cancer MR images. Our approach involves performing one-dimensional (1D) intra-slice SR reconstruction along the axial direction for both the sagittal and coronal planes, coupled with inter-slice SR reconstruction based on slice synthesis in the axial direction. To further enhance the accuracy of super-resolution reconstruction, we introduce a consistency supervision mechanism across the reconstruction results of different axes, promoting mutual learning between each axis. A key innovation of our method is the introduction of Depth-GAN for synthesize intermediate slices in the axial plane, incorporating depth information and leveraging Generative Adversarial Networks (GANs) for this purpose. Additionally, we enhance the accuracy of intermediate slice synthesis by employing a combination of supervised and unsupervised interactive learning techniques throughout the process. ResultsWe conducted extensive ablation studies and comparative analyses with existing methods to validate the effectiveness of our approach. On the test set from Shanxi Cancer Hospital, our method achieved a Peak Signal-to-Noise Ratio (PSNR) of 34.62 and a Structural Similarity Index (SSIM) of 96.34 %. These promising results demonstrate the superiority of our method.

High-resolution diffusion MRI of the cortico-cortical connections between lower visual areas reveals divergence of connections and enhanced connectivity of the central visual field representation

High-resolution diffusion MRI of the cortico-cortical connections between lower visual areas reveals divergence of connections and enhanced connectivity of the central visual field representation

Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI.

Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner. Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APPNL-F/NL-F: n = 36) and wild-type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (1H-MRS) in hippocampus and thalamus/hypothalamus using 9.4T preclinical MR scanner. GluCEST measurements revealed significant (p≤0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73±2.12%), hippocampus (11.29±2.41%), and hippocampal fimbriae (19.15±2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22±2.33%; p = 0.01) was also observed in 1H-MRS. GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism. Glutamate levels were monitored in different brain regions of early-stage Alzheimer's disease (AD) and wild-type male and female mice using glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI). Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus. Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause. These findings demonstrate previously unreported sex-specific glutamate changes in hippocampal sub-regions using high-resolution GluCEST MRI.

Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities).

Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort. We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors. The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD. ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline.

Diffusion Tensor Imaging in Boys With Adrenoleukodystrophy: Identification of Cerebral Disease and Association With Neurocognitive Outcomes.

Childhood cerebral adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease that must be treated at an early stage to prevent permanent brain injury and neurocognitive decline. In standard clinical practice, C-ALD lesions are detected and characterized by a neuroradiologist reviewing anatomical MRI scans. We aimed to assess whether diffusion tensor imaging (DTI) is sensitive to the presence and severity of C-ALD lesions and to investigate associations with neurocognitive outcomes after hematopoietic cell therapy (HCT). In this retrospective cohort study, we analyzed high-resolution anatomical MRI, DTI, and neurocognitive assessments from boys with C-ALD undergoing HCT at the University of Minnesota between 2011 and 2021. Longitudinal DTI data were compared with an age-matched group of boys with ALD and no lesion (NL-ALD). DTI metrics were obtained for atlas-based regions of interest (ROIs) within 3 subdivisions of the corpus callosum (CC), corticospinal tract (CST), and total white matter (WM). Between-group baseline and slope differences in fractional anisotropy (FA) and axial (AD), radial (RD), and mean (MD) diffusivities were compared using analysis of covariance accounting for age, MRI severity (Loes score), and lesion location. Among patients with NL-ALD (n = 14), stable or increasing FA, stable AD, and stable or decreasing RD and MD were generally observed during the 1-year study period across all ROIs. In comparison, patients with mild posterior lesions (Loes 1-2; n = 13) demonstrated lower baseline FA in the CC splenium (C-ALD 0.50 ± 0.08 vs NL-ALD 0.58 ± 0.04; pBH = 0.022 adjusted Benjamini-Hochberg p-value), lower baseline AD across ROIs (e.g., C-ALD 1.34 ± 0.03 ×10-9 m2/s in total WM vs NL-ALD 1.38 ± 0.04 ×10-9 m2/s; pBH = 0.005), lower baseline RD in CC body and CST, and lower baseline MD across ROIs except CC splenium. Longitudinal slopes in CC splenium showed high sensitivity and specificity in differentiating early C-ALD from NL-ALD. Among all patients with C-ALD (n = 38), baseline Loes scores and DTI metrics were associated with post-HCT neurocognitive functions, including processing speed (e.g., FA WM Spearman correlation coefficient R = 0.64) and visual-motor integration (e.g., FA WM R = 0.71). DTI was sensitive to lesion presence and severity as well as clinical neurocognitive effects of C-ALD. DTI metrics quantify C-ALD even at an early stage.

Assessing Cerebral Microvascular Volumetric Pulsatility with High-Resolution 4D CBV MRI at 7T.

Arterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.

Rare RNF213 variants is related to early-onset intracranial atherosclerosis: A Chinese community-based study

BackgroundThe relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. MethodsThe present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. ResultsNinety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (β = 0.150, P = 0.025) and numerical count of variants (β = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (β = 0.154, P = 0.014) and variant count (β = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. ConclusionsRare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.

Super-Resolving and Denoising 4D flow MRI of Neurofluids Using Physics-Guided Neural Networks.

To obtain high-resolution velocity fields of cerebrospinal fluid (CSF) and cerebral blood flow by applying a physics-guided neural network (div-mDCSRN-Flow) to 4D flow MRI. The div-mDCSRN-Flow network was developed to improve spatial resolution and denoise 4D flow MRI. The network was trained with patches of paired high-resolution and low-resolution synthetic 4D flow MRI data derived from computational fluid dynamic simulations of CSF flow within the cerebral ventricles of five healthy cases and five Alzheimer's disease cases. The loss function combined mean squared error with a binary cross-entropy term for segmentation and a divergence-based regularization term for the conservation of mass. Performance was assessed using synthetic 4D flow MRI in one healthy and one Alzheimer' disease cases, an in vitro study of healthy cerebral ventricles, and in vivo 4D flow imaging of CSF as well as flow in arterial and venous blood vessels. Comparison was performed to trilinear interpolation, divergence-free radial basis functions, divergence-free wavelets, 4DFlowNet, and our network without divergence constraints. The proposed network div-mDCSRN-Flow outperformed other methods in reconstructing high-resolution velocity fields from synthetic 4D flow MRI in healthy and AD cases. The div-mDCSRN-Flow network reduced error by 22.5% relative to linear interpolation for in vitro core voxels and by 49.5% in edge voxels. The results demonstrate generalizability of our 4D flow MRI super-resolution and denoising approach due to network training using flow patches and physics-based constraints. The mDCSRN-Flow network can facilitate MRI studies involving CSF flow measurements in cerebral ventricles and association of MRI-based flow metrics with cerebrovascular health.