All-optics technique for monitoring absolute cerebral blood flow: validation against magnetic resonance imaging perfusion.

Significance: The ability to monitor cerebral blood flow (CBF) at the bedside is essential to managing critical-care patients with neurological emergencies. Diffuse correlation spectroscopy (DCS) is ideal because it is non-invasive, portable, and inexpensive. We investigated a near-infrared spectroscopy (NIRS) approach for converting DCS measurements into physiological units of blood flow. Aim: Using magnetic resonance imaging perfusion as a reference, we investigated the accuracy of absolute CBF measurements from a bolus-tracking NIRS method that used transient hypoxia as a flow tracer and hypercapnia-induced increases in CBF measured by DCS. Approach: Twelve participants (7 female, 28 ± 6 years) completed a hypercapnia protocol with simultaneous CBF recordings from DCS and arterial spin labeling (ASL). Nine participants completed the transient hypoxia protocol while instrumented with time-resolved NIRS. The estimate of baseline CBF was subsequently used to calibrate hypercapnic DCS data. Results: Moderately strong correlations at baseline ( slope = 0.79 and R 2 = 0.59 ) and during hypercapnia ( slope = 0.90 and R 2 = 0.58 ) were found between CBF values from calibrated DCS and ASL (range 34 to 85 mL / 100 g / min ). Conclusions: Results demonstrated the feasibility of an all-optics approach that can both quantify CBF and perform continuous perfusion monitoring.

Measurement of blood-brain barrier water exchange rate using diffusion-prepared and multi-echo arterial spin labelling: Comparison of quantitative values and age dependence.

Water exchange rate (Kw) across the blood-brain barrier (BBB) is an important physiological parameter that may provide new insight into ageing and neurodegenerative disease. Recently, two non-invasive arterial spin labelling (ASL) MRI methods have been developed to measure Kw, but results from the different methods have not been directly compared. Furthermore, the association of Kw with age for each method has not been investigated in a single cohort. Thirty participants (70% female, 63.8 ± 10.4 years) were scanned at 3 T with Diffusion-Prepared ASL (DP-ASL) and Multi-Echo ASL (ME-ASL) using previously implemented acquisition and analysis protocols. Grey matter Kw, cerebral blood flow (CBF) and arterial transit time (ATT) were extracted. CBF values were consistent; approximately 50 ml/min/100 g for both methods, and a strong positive correlation in CBF from both methods across participants (r = 0.82, p < 0.001). ATT was significantly different between methods (on average 147.7 ms lower when measured with DP-ASL compared to ME-ASL) but was positively correlated across participants (r = 0.39, p < 0.05). Significantly different Kw values of 106.6 ± 19.7 min-1 and 306.8 ± 71.7 min-1 were measured using DP-ASL and ME-ASL, respectively, and DP-ASL Kw and ME-ASL Kw were negatively correlated across participants (r = -0.46, p < 0.01). Kw measured using ME-ASL had a significant linear relationship with age (p < 0.05). In conclusion, DP-ASL and ME-ASL provided estimates of Kw with significantly different quantitative values and inconsistent dependence with age. We propose future standardisation of modelling and fitting methods for DP-ASL and ME-ASL, to evaluate the effect on Kw quantification. Also, sensitivity and bias analyses should be performed for both approaches, to assess the effect of varying acquisition and fitting parameters. Lastly, comparison with independent measures of BBB water transport, and with physiological and clinical biomarkers known to be associated with changes in BBB permeability, are essential to validate the ASL methods, and to demonstrate their clinical utility.

Effect of Genetic Risk on the Relationship Between rs-fMRI Complexity and Tau and Amyloid PET in Alzheimer's Disease.

Reduced functional magnetic resonance imaging (fMRI)-complexity in Alzheimer's disease (AD) progression has been demonstrated and found to be associated with tauopathy and cognition. However, association of fMRI-complexity with amyloid and influence of genetic risk (APOEɛ4) remain unknown. Here we investigate the association between fMRI-complexity, tau-PET, and amyloid-PET as well as influence of APOE genotype using multivariate generalized linear models. We show that fMRI-complexity has a strong association with tau but not amyloid deposition and that the presence of an APOEɛ4 allele enhances this effect. Thus fMRI-complexity provides a surrogate marker of impaired brain functionality in AD progression.

Compromised Cerebral Arterial Perfusion, Altered Brain Tissue Integrity, and Cognitive Impairment in Adolescents with Complex Congenital Heart Disease.

(1) Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injuries in regions associated with cognitive deficits. Alteration in cerebral arterial perfusion (CAP), as measured by arterial transit time (ATT), may lead to perfusion deficits and potential injury. Our study aims to compare ATT values between CCHD patients and controls and assess the associations between ATT values, MD values, and cognitive scores in adolescents with CCHD. (2) Methods: 37 CCHD subjects, 14-18 years of age, who had undergone surgical palliation and 30 healthy controls completed cognitive testing and brain MRI assessments using a 3.0-Tesla scanner. ATT values and regional brain mean diffusivity [MD] were assessed for the whole brain using diffusion tensor imaging. (3) Results: The mean MoCA values [23.1 ± 4.1 vs. 28.1 ± 2.3; p < 0.001] and General Memory Index, with a subscore of WRAML2 [86.8 ± 15.4 vs. 110.3 ± 14.5; p < 0.001], showed significant cognitive deficits in CCHD patients compared to controls. The mean global ATT was significantly higher in CCHD patients versus controls (mean ± SD, s, 1.26 ± 0.11 vs. 1.19 ± 0.11, p = 0.03), respectively. The partial correlations between ATT values, MD values, and cognitive scores (p < 0.005) showed significant associations in areas including the hippocampus, prefrontal cortices, cerebellum, caudate, anterior and mid cingulate, insula, thalamus, and lingual gyrus. (4) Conclusions: Adolescents with CCHD had prolonged ATTs and showed correlation with clinical measurements of cognitive impairment and MRI measurements of brain tissue integrity. This suggests that altered CAP may play a role in brain tissue injury and cognitive impairment after surgical palliation.

MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults.

Vascular risk factors contribute to cognitive aging, with one such risk factor being dysfunction of the blood brain barrier (BBB). Studies using non-invasive magnetic resonance imaging (MRI) techniques, such as diffusion prepared arterial spin labeling (DP-ASL), can estimate BBB function by measuring water exchange rate (kw). DP-ASL kw has been associated with cognition, but the directionality and strength of the relationship is still under investigation. An additional variable that measures water in extracellular space and impacts cognition, MRI free water (FW), may help explain prior findings. A total of 94 older adults without dementia (Mean age = 74.17 years, 59.6% female) underwent MRI (DP-ASL, diffusion weighted imaging (DWI)) and cognitive assessment. Mean kw was computed across the whole brain (WB), and mean white matter FW was computed across all white matter. The relationship between kw and three cognitive domains (executive function, processing speed, memory) was tested using multiple linear regression. FW was tested as a mediator of the kw-cognitive relationship using the PROCESS macro. A positive association was found between WB kw and executive function [F(4,85) = 7.81, p < .001, R2= 0.269; ß = .245, p = .014]. Further, this effect was qualified by subsequent results showing that FW was a mediator of the WB kw-executive function relationship (indirect effect results: standardized effect = .060, bootstrap confidence interval = .0006 to .1411). Results suggest that lower water exchange rate (kw) may contribute to greater total white matter (WM) FW which, in turn, may disrupt executive function. Taken together, proper fluid clearance at the BBB contributes to higher-order cognitive abilities.

Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: Multi-site validation in the MarkVCID Consortium.

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis. METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. HIGHLIGHTS: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Deep Learning Denoising Improves CT Perfusion Image Quality in the Setting of Lower Contrast Dosing: A Feasibility Study.

BACKGROUND AND PURPOSE: Considering recent iodinated contrast shortages and a focus on reducing waste, developing protocols with lower contrast dosing while maintaining image quality through artificial intelligence is needed. This study compared reduced iodinated contrast media and standard dose CTP acquisitions, and the impact of deep learning denoising on CTP image quality in preclinical and clinical studies. The effect of reduced X-ray mAs dose was also investigated in preclinical studies. MATERIALS AND METHODS: Twelve swine underwent 9 CTP examinations each, performed at combinations of 3 different x-ray (37, 67, and 127 mAs) and iodinated contrast media doses (10, 15, and 20 mL). Clinical CTP acquisitions performed before and during the iodinated contrast media shortage and protocol change (from 40 to 30 mL) were retrospectively included. Eleven patients with reduced iodinated contrast media dosages and 11 propensity-score-matched controls with the standard iodinated contrast media dosages were included. A residual encoder-decoder convolutional neural network (RED-CNN) was trained for CTP denoising using k-space-weighted image average filtered CTP images as the target. The standard, RED-CNN-denoised, and k-space-weighted image average noise-filtered images for animal and human studies were compared for quantitative SNR and qualitative image evaluation. RESULTS: The SNR of animal CTP images decreased with reductions in iodinated contrast media and milliampere-second doses. Contrast dose reduction had a greater effect on SNR than milliampere-second reduction. Noise-filtering by k-space-weighted image average and RED-CNN denoising progressively improved the SNR of CTP maps, with RED-CNN resulting in the highest SNR. The SNR of clinical CTP images was generally lower with a reduced iodinated contrast media dose, which was improved by the k-space-weighted image average and RED-CNN denoising (P < .05). Qualitative readings consistently rated RED-CNN denoised CTP as the best quality, followed by k-space-weighted image average and then standard CTP images. CONCLUSIONS: Deep learning-denoising can improve image quality for low iodinated contrast media CTP protocols, and could approximate standard iodinated contrast media dose CTP, in addition to potentially improving image quality for low milliampere-second acquisitions.

Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases.

INTRODUCTION: We explored how blood-brain barrier (BBB) leakage rate of gadolinium chelates (Ktrans) and BBB water exchange rate (kw) varied in cerebral small vessel disease (cSVD) subtypes. METHODS: Thirty sporadic cSVD, 40 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 13 high-temperature requirement factor A serine peptidase 1 (HTRA) -related cSVD subjects were investigated parallel to 40 healthy individuals. Subjects underwent clinical, cognitive, and MRI assessment. RESULTS: In CADASIL, no difference in Ktrans, but lower kw was observed in multiple brain regions. In sporadic cSVD, no difference in kw, but higher Ktrans was found in the whole brain and normal-appearing white matter. In HTRA1-related cSVD, both higher Ktrans in the whole brain and lower kw in multiple brain regions were observed. In each patient group, the altered BBB measures were correlated with lesion burden or clinical severity. DISCUSSION: In cSVD subtypes, distinct alterations of kw and Ktrans were observed. The combination of Ktrans and kw can depict the heterogeneous BBB dysfunction. HIGHLIGHTS: We measured BBB leakage to gadolinium-based contrast agent (Ktrans) and water exchange rate (kw) across BBB in three subtypes of cSVD. CADASIL is characterized by lower kw, HTRA1-related cSVD exhibits both higher Ktrans and lower kw, while sporadic cSVD is distinguished by higher Ktrans. There are distinct alterations in kw and Ktrans among subtypes of cSVD, indicating the heterogeneous nature of BBB dysfunction.

Older adults with reduced cerebrovascular reactivity exhibit high white matter hyperintensity burden.

Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer's disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = -.02, 95% CI (-.04, -.008), p =.003] and in APOE4 carriers [B = -.03, 95% CI (-.06, -.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Functional connectivity and complexity analyses of resting-state fMRI in pre-adolescents demonstrating the behavioral symptoms of ADHD.

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), reward and motivation-related circuits (RMN), and salience network (SAL). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with the behavioral symptoms of ADHD, for pathology-relevant networks. We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children demonstrating the behavioral features of ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in the relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated. We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents demonstrating the behavior symptoms of ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in the FPN and RMN in the healthy controls however the association was absent in the participants demonstrating the behavior symptoms of ADHD. The current findings of complexity and FC in ADHD pathology support hypotheses of altered function of inhibitory control networks in ADHD.

Vessel density mapping of small cerebral vessels on 3D high resolution black blood MRI.

Small cerebral blood vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of small cerebral blood vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5 mm spatial resolution (interpolated from 0.51×0.51×0.64 mm3) at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Small cerebral blood vessels including small artery, arterioles, small veins, and venules on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of small cerebral blood vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

Regional differences in the link between water exchange rate across the blood-brain barrier and cognitive performance in normal aging.

The blood-brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61-84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Transformer-based deep learning denoising of single and multi-delay 3D arterial spin labeling.

PURPOSE: To present a Swin Transformer-based deep learning (DL) model (SwinIR) for denoising single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) and other Transformer-based methods. METHODS: SwinIR and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 66 subjects (119 scans) and tested on 39 subjects (44 scans) from three different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL, respectively. The performance was evaluated using similarity metrics, spatial SNR and quantification accuracy of cerebral blood flow (CBF), and arterial transit time (ATT). RESULTS: SwinIR outperformed CNN and other Transformer-based networks, whereas pseudo-3D models performed better than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models and further improved when using M0 as input, but introduced greater biases for CBF quantification. Pseudo-3D models with three slices achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay ASL, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps. CONCLUSIONS: SwinIR provided better performance than CNN and other Transformer-based methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.

Multi-Site Cross-Site Inter-Rater and Test-Retest Reliability and Construct Validity of the MarkVCID White Matter Hyperintensity Growth and Regression Protocol.

BACKGROUND: White matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease. OBJECTIVE: Conducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol. METHODS: The NINDS-supported MarkVCID Consortium evaluated a neuroimaging biomarker developed to track WMH change. Test-retest and cross-site inter-rater reliability of the protocol were assessed. Cognitive test scores were analyzed in relation to WMH changes to explore its construct validity. RESULTS: ICC values for test-retest reliability of WMH growth and regression were 0.969 and 0.937 respectively, while for cross-site inter-rater ICC values for WMH growth and regression were 0.995 and 0.990 respectively. Word list long-delay free-recall was negatively associated with WMH growth (p < 0.028) but was not associated with WMH regression. CONCLUSIONS: The present data demonstrate robust ICC validity of a WMH growth/regression protocol over a one-year period as measured by cross-site inter-rater and test-retest reliability. These data suggest that this approach may serve an important role in clinical trials of disease-modifying agents for VCID that may preferentially affect WMH growth, stability, or regression.

Functional Connectivity and Complexity Analyses of Resting-State fMRI in Pre-Adolescents with ADHD.

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), and reward and motivation-related circuits (RMN). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with ADHD for pathology-relevant networks. We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children with ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated. We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents with ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in fewer regions in the participants with ADHD than in the controls. The observation of reduced entropy is consistent with existing literature using rsfMRI and other neuroimaging modalities. The current findings of complexity and FC in ADHD support hypotheses of altered function of inhibitory control networks in ADHD.

Effect of corticosubcortical iron deposition on dysfunction in CADASIL is mediated by white matter microstructural damage.

Iron dysregulation may attenuate cognitive performance in patients with CADASIL. However, the underlying pathophysiological mechanisms remain incompletely understood. Whether white matter microstructural changes mediate these processes is largely unclear. In the present study, 30 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients were confirmed via genetic analysis and 30 sex- and age-matched healthy controls underwent multimodal MRI examinations and neuropsychological assessments. Quantitative susceptibility mapping and peak width of skeletonized mean diffusivity (PSMD) were analyzed. Mediation effect analysis was performed to explore the interrelationship between iron deposition, white matter microstructural changes and cognitive deficits in CADASIL. Cognitive deterioration was most affected in memory and executive function, followed by attention and working memory in CADASIL. Excessive iron in the temporal-precuneus pathway and deep gray matter specific to CADASIL were identified. Mediation analysis further revealed that PSMD mediated the relationship between iron concentration and cognitive profile in CADASIL. The present findings provide a new perspective on iron deposition in the corticosubcortical circuit and its contribution to disease-related selective cognitive decline, in which iron concentration may affect cognition by white matter microstructural changes in CADASIL.