Search

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Blood-brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer’s disease (AD), making non-invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB-ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population-based BBB-ASL permeability reference maps, and aimed to investigate associations between BBB-ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume

Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and ADrelated pathologies. Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, and the mechanisms by which it has been extended. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Gadolinium-based contrast agents (GBCA) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect of tumor grade, GBCA is repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is unwanted or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging, especially in vulnerable patient groups such as children, minimize risks of putative side effects, as well as benefit costs, logistics, and the environmental footprint. This review presents standard imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors, including the effect of prolonging follow-up intervals and omitting contrast-enhanced sequences. The potential of novel pulse sequences, such as arterial spin labeling, and upcoming artificial intelligence methods, e.g., to generate synthetic post-contrast images, promise to replace GBCA-dependent approaches. To attain a concise summary of the knowledge in the field, gliomas and meningiomas as typical representatives of primary brain tumors are the review’s focus. Special attention is paid to study quality and real-life applicability.

Purpose: Arterial Spin Labeling (ASL) is widely used in clinical research as a contrast-free MRI method for assessment of cerebral blood flow (CBF). While the recommended guideline for ASL acquisition is generally adopted to standardize quantification of CBF, ASL analysis still produces wide variability in CBF estimates, limiting research and clinical interpretation of ASL results. This study explored the extent of variability in ASL CBF quantification through the ISMRM OSIPI ASL MRI Challenge. The goal of the challenge was to minimize sources of variability in ASL analysis by establishing best practice in ASL data processing to make ASL analysis more reproducible and clinically meaningful. Methods: Eight international teams analyzed the challenge data consisting of a high-resolution T1- weighted anatomical image and ten pseudo-continuous ASL (PCASL) datasets. The datasets were simulated using an ASL digital reference object to produce ground-truth CBF values in normal and pathological states. The accuracy of CBF quantification from each team’s analysis was compared to ground-truth values across all voxels and within pre-defined brain regions. Reproducibility of CBF estimates across analysis pipelines was assessed using intra-class correlation coefficient (ICC), the limits of agreement (LOA) and the replicability of generating similar CBF estimates from the image processing approaches as documented. Results: The absolute errors in CBF estimates compared to the ground-truth synthetic data ranged from 18.36 to 48.12 ml/100g/min. Realistic motion incorporated in three of the ten synthetic data produced the largest absolute CBF error, largest variability between teams, and the least agreement (ICC and LOA) with ground truth results. Fifty percent (4/8) of the teams’ methods were replicated, and one method produced three times larger CBF errors (46.59 ml/100g/min) compared to submitted results. Conclusions: The apparent variability in CBF measurements, influenced by diff

BACKGROUND Breast cancer patients may experience cognitive difficulties after chemotherapy. PURPOSE To investigate whether an exercise intervention can affect cerebral blood flow (CBF) in breast cancer patients and if CBF changes relate to memory function. STUDY TYPE Prospective. POPULATION Chemotherapy-treated breast cancer patients with cognitive problems, and with relatively low physical activity levels were randomized to an exercise intervention (n=91) or control group (n=90). FIELDSTRENGTH/SEQUENCE A 3-T arterial spin labeling CBF scan was performed. ASSESSMENT The 6-month intervention consisted of (supervised) aerobic and strength training, 4x1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after six months included the arterial spin labeling CBF scan, from which we calculated gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Furthermore, we measured physical fitness and memory functioning. STATISTICAL TESTS Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS We observed significant improvement in physical fitness (VO2peak) in the intervention group (n=53) compared to controls (n=51, B1.47, 95%CI:0.44; 2.50), nevertheless no intervention effects on CBF were found (e.g. whole brain: B0.98, 95%CI:-2.38; 4.34). Highly fatigued patients showed larger, but not significant, treatment effects. Additionally, change in physical fitness, from baseline to post-intervention, was positively associated with changes in CBF (e.g., whole brain: B0.75, 95%CI:0.07; 1.43). However, we observed no relation between CBF changes and change in memory performance. DATA CONCLUSION The exercise intervention did not affect CBF of cognitively affected breast cancer patients. However, a change in physical fitness was related to a change in CBF, but a change in CBF was not associated with memory functioning.

The 2015 consensus statement published by the ISMRM Perfusion Study Group and the EU COST Action ‘ASL in Dementia’ aimed to encourage the implementation of robust Arterial Spin Labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task-Force has been working on the development of an ‘ASL Lexicon and Reporting Recommendations’ for perfusion imaging and analysis, aiming to 1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as the physiological constants required for quantitative analysis, and 2) provide a community-endorsed recommendation on the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/articles. In this manuscript, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Purpose: To create an inventory of automated image processing pipelines of Arterial Spin Labeling (ASL) and summarize their features and accessibility for users to choose an optimal pipeline to fit their needs. Methods: Pipeline developers were invited to self-assess their pipelines using a questionnaire developed by the Task Force 1.1 of the Open Science Initiative for Perfusion Imaging (OSIPI). Additionally, publicly available pipelines were evaluated by two independent testers using an objective unified scoring system. The testing focused on the capability, flexibility, and ease of use of the pipelines on various datasets. Results: The developers of twenty-one pipelines filled in the questionnaire. Most pipelines support data from the three major vendors, i.e., GE (n=15), Philips (n=15), and Siemens (n=16), are free for research (n=18), work with the standard neuroimaging data format NIfTI (n=15), and can process standard 3D single PLD pseudo-continuous ASL images (n=21). Pipelines mainly differed in their support of advanced sequences and advanced features. Nine publicly available pipelines were included in the independent testing. Whereas certain pipelines were easy to use for users without programming skills, other pipelines offered more flexibility for configuring advanced processing options. Conclusion: ASL data from the most commonly used ASL sequences saved in the standard neuroimaging data formats can be easily processed using publicly available pipelines. A specific choice of a pipeline should consider specific requirements on features and users’ skills, and the ASL inventory can serve as a valuable guide to facilitate this choice.

Genetic frontotemporal dementia is most commonly attributable to mutations in the C9orf72, GRN, or MAPT genes. The disease has near-complete penetrance, making presymptomatic carriers an ideal population for ascertaining the earliest changes in disease progression and the identification of suitable biomarkers for designing therapeutic trials when minimal neuronal loss has occurred. Cerebral perfusion, as measured by arterial spin labelling (ASL) MRI, has shown promise in being one such biomarker. However, longitudinal profiles of change in perfusion over time in presymptomatic carriers across all three genetic subgroups are lacking. Using data from the multicenter GENetic Frontotemporal dementia Initiative, we investigated longitudinal profiles of cerebral perfusion using ASL-MRI in C9orf72 (n = 42), GRN (n = 70), and MAPT (n = 31) presymptomatic mutation carriers and non-carrier controls (n = 158). ASL and T1w scans were processed with the ExploreASL pipeline to produce partial volume corrected perfusion images, which were parcellated to extract mean perfusion values from whole brain grey matter and regions defined by the second version of the automated anatomical atlas (AAL2). Linear mixed effects models were used to assess longitudinal perfusion change. Mutation carrier groups and non-carriers were statistically indistinguishable by baseline demographic and clinical measures. Decline in whole brain grey matter perfusion over time was more pronounced in all three carrier subgroups relative to controls, with changes most pronounced in GRN, followed by C9orf72 and MAPT variants. Additionally, GRN and MAPT groups featured global grey matter hypoperfusion relative to non-carrier controls as early as one year after baseline measurement, with C9orf72 featuring significant hypoperfusion after two years. Region of interest analysis demonstrated that each genetic subgroup had its own regional profile in terms of longitudinal perfusion decline. Perfusion decline in C9orf72

Background: Decreased cerebral blood flow (CBF) and deterioration of blood-brain barrier (BBB) are suggested to be precursor conditions of cognitive impairment. Using a novel multi-echo-time arterial spin labelling (ASL) protocol, we examined the time of exchange (Tex) of water across the BBB as a measurement of BBB permeability. We further examined the association of cardiovascular risk factors with Tex in an ongoing cohort study. Method: Data (n=29, mean age: 55.9±6.1years, 69% women) were drawn from Neurological biomarkers of Blood, MRI and Cognition (NEURO-BMC) study performed at National University of Singapore. NEURO-BMC is an ongoing prospective cohort study (age: 45-65 years) on brain changes in a subclinical phase of cognitive impairment. A multi-echo, Hadamard-encoded multi-post-labelling-delay pseudo-continuous ASL (PCASL) protocol was used on a 3T scanner. ExploreASL was used with a modified version of FSL FABBER(4) to quantify cerebral blood flow (CBF), arterial transit time (ATT), and Tex. ASL-extracted parameters were compared with cardiovascular risk parameters such as blood pressure (BP), BMI and smoking status. Result: High systolic and diastolic BP were associated with significantly reduced Tex (Fig 1). Additionally, higher systolic and diastolic BP showed a trend of increased ATT and reduced CBF, though the associations were not statistically significant (Table 1). High BMI had a significant association with increased ATT and reduced CBF. However, no trend was observed between BMI and Tex. Participants who ever smoked were observed to have a reduced Tex and CBF and increased ATT, but statistical significance was only found for CBF (Fig 1). Conclusion: In this pilot study, we showed that BBB-ASL-derived parameters - ATT, CBF, and Tex - were associated with BP, BMI, and smoking status. While the sample size for this preliminary analysis was too small to make a definitive conclusion as not all associations were statistically significant, all studied

Blood-brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer’s disease (AD), making non-invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB-ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population-based BBB-ASL permeability reference maps, and aimed to investigate associations between BBB-ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume

Cardiovascular and cerebrovascular pathology may accelerate brain aging and cognitive decline. Structural cerebrovascular imaging biomarkers, such as white matter hyperintensities, reflect mostly irreversible accumulated damage. In contrast, cerebral blood flow (CBF), measured with arterial spin labelling (ASL) perfusion MRI, is a potential early haemodynamic biomarker of cognitive impairment. However, our understanding of physiological CBF variability and its relation with cognition is limited.

Subtle changes in BBB integrity might be missed by contrast-enhanced T1-weighted MRI. Blood-brain barrier arterial spin labeling (BBB-ASL) is a new technique to assess BBB disruptions. In this work, we measured the cerebral blood flow (CBF) and exchange time (Tex) values of the tumor, normal-appearing white matter, and normal-appearing gray matter regions in gliomas using BBB-ASL technique. Our results indicated higher CBF and leakier BBB in contrast-enhanced regions of gliomas than in the normal-appearing GM.

Arterial transit artifacts (ATAs) in arterial spin labeling (ASL) images are common in populations with prolonged arterial transit time (ATT) and may be associated with vascular insufficiency. The spatial coefficient of variance (sCoV) of ASL images can quantify the presence of these artifacts. Vascular insufficiency could contribute to the development of white matter hyperintensities (WMH), a common marker of cerebral small vessel disease. We demonstrated that baseline sCoV of CBF is associated with WMH at baseline and predicts WMH volume change, in a cognitively unimpaired population of 88 subjects.

Decreased cerebral blood flow (CBF) and deterioration of blood-brain barrier (BBB) are suggested to be precursor conditions of cognitive impairment. Using a novel multi-echo-time arterial spin labelling (ASL) protocol, we examined the time of exchange (Tex) of water across the BBB as a measurement of BBB permeability. We further examined the association of cardiovascular risk factors with Tex in an ongoing cohort study.

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is time of exchange (Tex) of water across the BBB as measured by multi-echo arterial spin labeling MRI. We evaluated Tex across the age spectrum in 40 adults from two cohorts of healthy controls, and demonstrated that Tex is higher in gray than in white matter, higher in females than in males, and that Tex decreases with age. These findings suggest that BBB permeability changes over the lifespan can be investigated using arterial spin labeling approaches.

One of the earliest signs of Alzheimer’s disease (AD) is the loss of blood-brain barrier (BBB) integrity. Arterial spin labeling (ASL) MRI is a non-invasive way to measure perfusion and several other hemodynamic and physiological parameters, including vascular permeability. The DEveloping BBB-ASL as non-Invasive Early biomarker (DEBBIE) consortium aims to develop and integrate innovative techniques to allow robust BBB permeability assessments by ASL to develop a sensitive, non-invasive, and early biomarker for AD and related dementias. This work summarizes our planned efforts to develop and establish an MRI-based BBB permeability biomarker.

While mid-life cardiovascular pathology may lead to late-life cognitive decline, our understanding of the role of cerebrovascular health as an intermediate biomarker is limited. We explored the association between cardiovascular health biomarkers and cross-sectional and longitudinal cerebrovascular health assessed by ASL MRI in Insight46, a well-characterised cognitively normal population-based sample. We found several cross-sectional and longitudinal associations between blood pressure and CBF. These findings suggest that the effects of BP on cerebrovascular health can be imaged with ASL perfusion MRI, possibly offering opportunities to prevent or intervene before cognitive decline sets in.

Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesized to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Arterial spin labeling (ASL) perfusion MRI has recently been adapted to map the BBB permeability non-invasively. This article outlines the study design of the DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium, focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods: DEBBIE-AD consists of 13 cohorts enrolling participants from subjective cognitive decline to AD, as well as healthy controls across the lifespan. The reproducibility and accuracy of BBB-ASL will be evaluated in healthy participants, and its clinical value will be evaluated with both established and novel AD biomarkers. Expected endpoints: DEBBIE-AD aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies, which may provide new targets for treatment.

This review article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 the consensus paper on ASL. While the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and o clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, tumors, neurodegenerative disease, pediatric applications, and seizures/epilepsy, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications where ASL can provide unique diagnostic information. This guidance is intended for anyone interested in using ASL in a routine clinical setting — i.e., on a single-subject basis rather than in cohort studies — building on the previous ASL consensus review.

Background: The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to the brain parenchyma, protecting the brain’s microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Main body: Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging across all settings, particularly in resource-limited settings? Conclusion: BBB imaging holds the potential to enable earlier diagnosis and aid in the recruitment of individuals and rapid assessment of treatment response in clinical trials. Further advances are needed, such as the validation, standardization, and implementation of readily available, low-cost, and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.

To date, perfusion simulations in the human brain have been limited to a relatively small number of patient-specific cases. Here, a pipeline relying on magnetic resonance imaging (MRI) is proposed to overcome this limitation. The computational geometry is adjusted using T1-weighted MRI, whereas the perfusion model parameters are tuned based on arterial spin labeling perfusion MRI. A cohort of 75 patients is considered to demonstrate that the pipeline is suitable to generate virtual patients with statistically realistic cerebral blood flow maps. In the future, in silico clinical trials will be conducted using similar virtual cohorts to improve ischaemic stroke interventions.

BACKGROUND Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications in patients with brain tumors. PURPOSE To investigate whether cerebral APT-CEST is sufficiently reproducible in healthy tissue and glioma for clinical use at 3T. STUDY TYPE Prospective, longitudinal SUBJECTS Twenty-one healthy volunteers (M:F = 10:11; age 39±11 years) and six glioma patients (M:F = 3:3; age 50±17 years: four glioblastomas, one oligodendroglioma, one suspected low-grade glioma). FIELD STRENGTH/SEQUENCE 3T, SPACE-CEST ASSESSMENT APT-CEST measurement reproducibility was assessed within-session (glioma patients, healthy volunteers), and between-sessions and between-days (healthy volunteers). The standard deviation of the within-subject difference (SDdiff) was calculated in tumor regions of interest (ROI), and eight ROIs at relevant locations including a whole-brain ROI. STATISTICAL TESTS Brown-Forsythe tests and variance component analyses (VCA) were used to assess the reproducibility of ROIs for the three reproducibility time intervals. Intraclass correlation coefficient (ICC) was used to assess agreement between the ROIs for the three reproducibility time intervals. RESULTS APT-CEST magnetization transfer ratio asymmetry (MTRasym) was 0.89±0.96% on average in healthy brain tissue and 1.59±0.67% in tumor tissue. Intratumoral mean MTRasym was significantly higher than MTRasym in healthy-appearing tissue in patients (0.5±0.46%; P< 0.001). The APTCEST difference between GBMs and contralateral tissue was 1.11%. The average within-session, between-sessions, and between-days SDdiff of healthy control brains was 0.2%. The within-session SDdiff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. The orbitofrontal gyri were the ROI with the highest within-session SDdiff (0.61%). Within-session reproducibility of ROIs did not differ significantly from between-sessions or

Background: Biological brain age estimates from structural MRI data and their difference from chronological age — the brain age gap (BAG) — have been successfully applied in a range of diseases, but remain limited to capturing structural characteristics only. To incorporate physiological properties, we operationalized ‘Cerebrovascular brain age’ using a combination of structural, and arterial spin labelling (ASL) image data, investigate their optimal feature and algorithm combinations, and evaluate its repeatability. Methods: Healthy participants (n = 341, 62 % female, age 59.7 ± 14.8 years, range: 21 - 95 years) were scanned at baseline and after 1.7 ± 0.5 years (n = 248, 62.9 % female, mean age 62.4 ± 13.3 years, range: 27 - 86). At 3 T MRI, 3D structural T1-weighted (T1w) and Fluid Attenuated Inversion Recovery (FLAIR), and 3D ASL image data were acquired to extract within grey matter (GM) and deep white matter (WM) ROIs: volumetrics, WM hyperintensity volume and count; and cerebral blood flow (CBF) and spatial coefficient of variation (CoV). Multiple combinations of features and machine learning algorithms were evaluated to train brain age algorithms on 70 % of the subjects and evaluated on the remainder, for 300 Monte-Carlo cross-validations, using the Mean Absolute Error (MAE). Feature importance of the best performing model was assessed by determining the feature weights. Model repeatability of the best model was assessed by comparing the BAGs between baseline and follow-up, also using T1w + FLAIR or ASL-only features. Results: The lowest MAE was observed for the ElasticNetCV algorithm using T1w + FLAIR + ASL (MAE = 5.03 ± 0.34 years) and significantly better compared to using T1w + FLAIR (MAE = 6.01 ± 0.39, p < 0.01) and ASL-only features (MAE = 6.04 ± 0.39, R2 = 0.70 ± 0.04, p < 0.01). The three most important features were GM CBF (6.2 ± 1.18), GM/ICV (5.34 ± 0.6), and WM CBF (4.16 ± 0.36). Average baseline and follow-up BAGs were not different (-1.51 ± 6.2

ASL was invented pre-clinically in 19901. The first human applications appeared in 1996 when the post-labeling delay (PLD) was introduced to compensate for the larger distance between labeling in the neck and readout in the brain2. The initially low clinical reliability improved with the implementation of background suppression in 19993,4, the increasing availability of 3T MRI, and the invention of pseudo-continuous ASL in 20085. In 2012, the European COST-action BM1103 "ASL In Dementia” was founded and worked towards reducing the ASL differences between MRI scanners to improve between-center reproducibility. Together with other ISMRM ASL investigators, this resulted in the 2014 consensus paper that recommended single-PLD PCASL with a 3D readout, background suppression, no vascular crushing, the acquisition of a separate M0 image, and a simplified single-compartment quantification model for clinical ASL6.

Dear Editor, We have read the letter to the editor from Long et al. with great interest. 1 The authors of this letter stated two methodological concerns on which we will respond. The first concern is that objective criteria are missing for true trigonocephaly or benign metopic ridge. We only included moderate to severe trigonocephaly patients according to the definitions of Birgfeld et al2. Birgfeld et al. provide both a phenotypical distinction between benign metopic ridge and metopic synostosis in their article, as well as illustrative photographs with corresponding CT-imaging in Figure 1.2 Cho et al. and Anolik et al. described CT measures to assess severity of metopic synostosis. In both articles the cut-off point to determine surgical indication remains subjective and poor consensus for the intermediate presentation of metopic craniosynostosis is found.3, 4 In addition, Sisti et al. recently reviewed all literature in Pubmed on trigonocephaly, relating to 15 anthropometric cranial measurements for surgical indications.5 This study illustrates that most papers have a lack of diagnostic criteria for trigonocephaly.5 At our center, the decision for surgery is made through shared decision making with parents. In 2021 this resulted in surgery for 14 patients (moderate or severe presentation) and a conservative treatment for 40 patients (18 mild, and 22 moderate or severe presentation). The second raised concern is the potential blunting effect of sevoflurane on CBF. If it does, a similar effect on both the patients and controls is expected. In our previous ASL study in patients with syndromic craniosynostosis using the same sedation protocol, we found a difference between the groups.6 This suggests that the normal findings in patients with trigonocephaly reflect normal CBF. Very few studies have investigated the influence of anesthesia on ASL CBF in the pediatric population. Carsin-Vu et al. included 84 subjects from 6 months to 15 years and showed no significant CB

Item does not contain fulltext, BACKGROUND: The arterial spin labeling-spatial coefficient of variation (sCoV) is a new vascular magnetic resonance imaging (MRI) parameter that could be a more sensitive marker for dementia-associated cerebral microvascular disease than the commonly used MRI markers cerebral blood flow (CBF) and white matter hyperintensity volume (WMHV). METHODS: 195 community-dwelling older people with hypertension were invited to undergo MRI twice, with a three-year interval. Cognition was evaluated every two years for 6-8 years using the mini-mental state examination (MMSE). We assessed relations of sCoV, CBF and WMHV with cognitive decline during follow-up. We also registered dementia diagnoses, up to 9 years after the first scan. In an additional analysis, we compared these MRI parameters between participants that did and did not develop dementia. RESULTS: 136/195 completed the second scan. sCoV and CBF were not associated with MMSE changes during 6-8 years of follow-up. Higher WMHV was associated with declining MMSE scores (-0.02 points/year/ml, 95%CI=-0.03 to -0.00). ScOv and CBF did not differ between participants who did (n=15) and did not (n=180) develop dementia, whereas higher WMHV was reported in participants who developed dementia after the first MRI (13.3 vs 6.1mL, p<0.001). There were no associations between longitudinal change in any of the MRI parameters and cognitive decline or subsequent dementia. CONCLUSION: Global sCoV and CBF were less sensitive longitudinal markers of cognitive decline and dementia compared to WMHV in community-dwelling older people with hypertension. Larger longitudinal MRI perfusion studies are needed to identify possible (regional) patterns of cerebral perfusion preceding cognitive decline and dementia diagnosis.

Image-derived phenotypes (IDPs) from multimodal MRI sequences constitute an important resource that allows the characterization of brain alterations in the early stages of Alzheimer diseases and other neurodegenerative conditions. Here, we showed the computation of multimodal IDPs from the European Prevention of Alzheimer Dementia (EPAD) cohort and assessed their relationship with non-imaging markers of neurodegeneration. We demonstrated the clinical relevance of IDPs to uncover early brain alteration in AD by showing expected association with non-imaging data.

Aim/Introduction: Blood-brain barrier (BBB) breakdown has been suggested to be an early biomarker of cognitive dysfunction. Currently, PET using [15O]-water and [11C]-Butanol is the standard for measuring BBB permeability. Arterial Spin Labeling (ASL) MRI is a promising alternative as no exogenous contrast is used. This study will validate BBB-ASL MRI by comparing it with PET and assess if BBB-ASL indeed robustly quantifes BBB permeability. Here we present our protocol and preliminary results using image-derived input function (IDIF) to quantify BBB-PET, noninvasively. Materials and Methods: Integrated PET/MR imaging provides a unique opportunity to assess - for the frst time - the ability of ASL to noninvasively image BBB permeability by comparing it to PET in the same subjects and under the same conditions. First, the BBBASL (1) sensitivity in pigs will be investigated by mimicking BBB dysfunction using an Aquaporin-4 inhibitor that will block the fow of water (2). Absolute BBB measurements (as obtained by arterial sampling) will be compared to BBB-ASL measurements. Second, to determine whether any changes in BBB permeability measured by MRI translate to humans, permeability measured by PET and MRI in 10 ischemic stroke patients will be compared. Third, the accuracy of BBB-ASL will be assessed in humans with subtle BBB dysfunction in 12 patients with Alzheimer’s disease, 12 with mild cognitive impairment and 12 age-matched controls. Results: While the preclinical validation studies are underway, we evaluated our PET/MRI IDIF approach (3) for absolute PET quantifcation to eliminate the need for arterial sampling in the two clinical studies. In three pigs, the [15O]-water PET/MR IDIFs were similar to arterial-sampled input functions with area-under-the-curve ratio (IDIF/AIF) of 1.03 - 1.1, demonstrating the potential of IDIF for BBB permeability estimates. Conclusion: The goal of this work is twofold. On one hand, it will demonstrate the potential of ASL measurement

Recent findings suggest additive effects of cerebrovascular disease and Alzheimer's disease (AD) on cognitive decline. MR imaging of cerebral blood flow holds great promise as an early dementia biomarker. Supply and demand of blood flow in the brain can be affected by, respectively, the loss of vascular health and the decrease of neuronal activity, as a consequence of AD. This study investigates to what extent vascular and AD components affect CBF and how they interact with each other.

The 2015 consensus statement1 published by the ISMRM Perfusion Study Group and the EU COST Action ‘ASL in Dementia’ aimed to encourage the implementation of robust Arterial Spin Labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL (PCASL) sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, both in terms of improving the accuracy of cerebral blood flow (CBF) quantification and providing other output derivatives in addition to CBF. These advances have greatly expanded the scope of ASL, but also bring further divergence of the technique, particularly in the terminology used, which can lead to confusion and hamper research reproducibility. As part of the Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ‘ASL Perfusion Imaging and Analysis Lexicon and Reporting Recommendations’, aiming: 1) to develop standardized nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as the physiological constants required for quantitative analysis, and 2) to provide a community-endorsed recommendation on a minimal list of parameters that should be reported in publications.

Background: Arterial spin-labeling (ASL) is a viable non-invasive alternative to dynamic susceptibility contrast (DSC) for measuring cerebral blood flow (CBF). While quantitative accuracy of ASL and DSC was compared in healthy volunteers and patients, a comparison to a reference standard in patients diagnosed with glioma is still missing. Purpose: To probe the quantitative agreement between perfusion measurements based on ASL and DSC in comparison to the gold standard of PET in patients with glioma. Materials and Methods: This secondary analysis included pre-surgical ASL and DSC perfusion measurements in participants diagnosed with grade 2-4 gliomas drawn from the prospective FRONTIER study (Dutch National Trial Register - NTR5354) and compared the two techniques with the gold-standard perfusion measurement 15O-H2O-PET. The quantitative comparison was performed both in normal-appearing tissue as well as in the tumor region. The mean, maximum, and voxel-wise perfusion values were with and without normalization to normal-appearing tissue. And finally, a qualitative analysis was performed on individual cases to help interpret the quantitative results. Results: Eight patients (age 40.5 ± 17.0 years, 3 women) were analyzed. ASL showed better voxel-wise agreement with PET in the normal-appearing tissue than DSC (mean relative error of 26.8% vs. 33.8%). Within the tumor, cerebral blood flow (CBF) normalized contralateral gray matter showed similar tumor maximum values in both techniques - mean relative error of 23.2% for ASL and 22.0% for DSC. However, the mean relative error on a voxel-wise basis was better for ASL (27.2%) than for DSC (35.0%). Qualitatively, ASL tended to overestimate CBF in macrovessels, and DSC tended to overestimate CBF in non-enhancing tumors with small vessel diameters. Conclusion: While neither ASL nor DSC can readily replace 15O-H2O-PET in tumor quantitative perfusion measurement, ASL CBF presents a viable non-invasive semi-quantitative alternativ

Brain-age estimates the biological brain age from structural MRI images based on changes in brain-tissue integrity and irreversible structural changes [1]. The brain-age offset to the chronological age — the age gap — is associated with cognitive pathology [2]. Adding vascular or functional MRI biomarkers may add sensitivity to physiological and metabolic changes, complementing and improving structural brain-age, and possibly improving its sensitivity to earlier disease changes. Arterial spin labeling (ASL) MRI is a potential early biomarker of cerebrovascular health and correlates with the initial stages of cognitive pathology [3]. Here, we propose the ‘Cerebrovascular Brain-age’ as a combination of T1w, FLAIR, and ASL image features composed of the spatial Coefficient of Variation (CoV) and vascular-territory derived (VT) cerebral blood flow (CBF).

ASL-MRI is reported as an option to assess potentially heterogeneous physiological processes important for tumour treatment. Therefore, we explored the heterogeneity in normalised CBF as an imaging biomarker for assessment of treatment effect in pLGG. There is a noticeable effect of chemotherapy observed as a change in texture of healthy appearing brain tissue. A high difference in texture between treated and non-treated patients for non-enhancing tumour part is observed, suggesting that texture, based on co-occurrence matrices, is suitable as an imaging biomarker for assessment of treatment effect in pLGG.

The OSIPI ASL MRI Challenge is an initiative of the ASL community aiming to characterize the variability of CBF quantification arising from different pipelines. The goal of this challenge is to establish best practice in ASL data processing, understand the sources of variability, make ASL analysis more reproducible, and enable fair comparison between studies. Here, we analyzed 3 submitted entries from 7 teams registered in the challenge. The preliminary results showed pipelines based in different programming languages and analysis tools, leading to important variability in the quantitative CBF maps compared to the ground-truth.

3D PCASL scans were acquired for seventeen aging, retired professional football players with a history of head traumas. Left, right and bilateral CBF and ASL spatial coefficient of variation (sCoV) values were examined for twelve concussion-related ROIs. A Z-scoring approach was applied, with outliers defined as mild, moderate, or severe injury burden (IB). An IB symmetry index was also calculated. Outliers were detected in all 12 ROIs, and the anterior parahippocampal gyrus and inferior frontal gyrus pars opercularis had the highest CBF and ASL sCoV IB, respectively. IB was not biased towards the left or right hemisphere.

Cerebral perfusion models were found to be promising research tools to predict the impact of acute ischaemic stroke and related treatments on cerebral blood flow (CBF) linked to patients’ functional outcome. To provide insights relevant to clinical trials, perfusion simulations need to become suitable for group-level investigations, but computational studies to date have been limited to a few patient-specific cases. This study set out to overcome issues related to automated parameter inference, that restrict the sample size of perfusion simulations, by integrating neuroimaging data. Seventy-five brain models were generated using measurements from a cohort of 75 healthy elderly individuals to model resting-state CBF distributions. Computational perfusion model geometries were adjusted using healthy reference subjects’ T1-weighted MRI. Haemodynamic model parameters were determined from CBF measurements corresponding to arterial spin labelling perfusion MRI. Thereafter, perfusion simulations were conducted for 150 acute ischaemic stroke cases by simulating an occlusion and cessation of blood flow in the left and right middle cerebral arteries. The anatomical (geometrical) fitness of the brain models was evaluated by comparing the simulated grey and white matter (GM and WM) volumes to measurements in healthy reference subjects. Statistically significant, strong positive correlations were found in both cases (GM: Pearson’s r 0.74, P-value< 0.001; WM: Pearson’s r 0.84, P-value< 0.001). Haemodynamic parameter tuning was verified by comparing total volumetric blood flow rate to the brain in reference subjects and simulations resulting in Pearson’s r 0.89, and P-value< 0.001. In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based proxy was 197±25 ml. Computational results showed excellent agreement with anatomical and haemodynamic literature data corresponding to T1-weighted, T2-weighted, and phase-contrast MRI measurements both in healthy scen

Arterial spin labeling (ASL) is a non-invasive and cost-effective MRI technique for brain perfusion measurements. While it has developed into a robust technique for scientific and clinical use, its image processing can still be daunting. The 2019 Ann Arbor ISMRM ASL working group established that education is one of the main areas that can accelerate the use of ASL in research and clinical practice. Specifically, the post-acquisition processing of ASL images and their preparation for region- of-interest or voxel-wise statistical analyses is a topic that has not yet received much educational attention. This educational review is aimed at medical and technical researchers with an interest in ASL image processing and analysis. We provide summaries of all typical ASL processing steps on both single-subject and group levels. The readers are assumed to have a basic understanding of cerebral perfusion (patho)physiology; a basic level of programming or image analysis is not required. Starting with an introduction of the physiology and MRI technique behind ASL, and how they interact with the image processing, we present an overview of processing pipelines and explain the specific ASL processing steps. Example video and image illustrations of ASL studies of different cases, as well as model calculations, help the reader develop an understanding of which processing steps to check for their own studies. Some of the educational content can be extrapolated to the processing of other MRI data. We anticipate that this educational review will help accelerate the application of ASL MRI for clinical brain research.

Background: Cognitive decline in older adults has been attributed to reduced cerebral blood flow (CBF). Recently, the spatial coefficient of variation (sCoV) of ASL has been proposed as a proxy marker of cerebrovascular insufficiency. We investigated the association between baseline ASL parameters with cognitive decline, incident cerebrovascular disease and risk of vascular events and mortality. Design, Setting and Participants: 368 memory-clinic patients underwent three-annual neuropsychological assessments and brain MRI scans at baseline and follow-up. MRIs were graded for white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), cortical infarcts and intracranial stenosis. Baseline gray (GM) and white matter (WM) CBF and GM-sCoV were obtained with ExploreASL from 2D-EPI pseudo-continuous ASL images. Cognitive assessment was done using a validated neuropsychological battery. Data on incident vascular events (heart disease, stroke, transient ischemic attack) and mortality were obtained. Results: Higher baseline GM-sCoV was associated with decline in the memory domain over three years of follow-up. Furthermore, higher GM-sCoV was associated with a decline in the memory domain only in participants without dementia. Higher baseline GM-sCoV was associated with progression of WMH and incident CMBs. During a mean follow-up of 3 years, 29 (7.8%) participants developed vascular events and 18 (4.8%) died. Participants with higher baseline mean GM-sCoV were at increased risk of vascular events. Conclusions: Higher baseline GM-sCoV of ASL was associated with a decline in memory and risk of incident cerebrovascular disease and vascular events, suggesting that cerebrovascular insufficiency may contribute to accelerated cognitive decline and worse clinical outcomes in memory clinic participants.

Background. The arterial spin labeling-spatial coefficient of variation (sCoV) is a new vascular magnetic resonance imaging (MRI) parameter that could be a more sensitive marker for dementia-associated cerebral microvascular disease than the commonly used MRI markers cerebral blood flow (CBF) and white matter hyperintensity volume (WMHV). Methods. 195 community-dwelling older people with hypertension underwent MRI twice with a three-year interval. Cognition was evaluated every two years for 6-8 years using the mini-mental state examination (MMSE). Dementia diagnoses were registered up to 9 years after the first scan. We assessed relations of sCoV, CBF and WMHV with cognitive decline during follow-up, and compared MRI parameters between participants that did and did not develop dementia. Results. sCoV and CBF were not associated with MMSE changes during 6-8 years of follow-up and did not differ between participants who did (n=15) and did not (n=180) develop dementia. Higher WMHV was associated with declining MMSE scores (-0.15 points/year/ml, 95%CI=-0.30; -0.01), and with participants who developed dementia after the first MRI (13.3 vs 6.1mL, p<0.001). There were no associations between longitudinal change in any of the MRI parameters and cognitive decline or subsequent dementia. Conclusion. Global sCoV and CBF were less sensitive longitudinal markers of cognitive decline and dementia compared to WMHV in community-dwelling older people with hypertension. Larger longitudinal MRI perfusion studies are needed to identify possible (regional) patterns of cerebral perfusion preceding cognitive decline and dementia diagnosis.

Arterial spin labeling (ASL) is a non-invasive MRI technique, allowing quantitative measurement of cerebral perfusion. Incomplete or inaccurate reporting of acquisition parameters complicates quantification, analysis, and sharing of ASL data, particularly for studies across multiple sites, platforms, and ASL methods. Therefore, there is a strong need for standardization of ASL data storage, including acquisition metadata. Recently ASL-BIDS, the BIDS extension for ASL, was developed and released in BIDS 1.5.0. This manuscript provides an overview of the development and design choices of this first ASL-BIDS extension, which is mainly aimed at clinical ASL applications. The structure of the ASL data, focusing on storage order of the ASL time series and implementation of calibration approaches, unit scaling, ASL-related BIDS fields, and storage of the labeling plane information, are discussed. Additionally, an overview of ASL-BIDS compatible conversion and ASL analysis software and ASL example datasets in BIDS format is provided. It is anticipated that large-scale adoption of ASL-BIDS will improve the reproducibility of ASL research.

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer’s Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI pre- processing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features — i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features — Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) — were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses.

Background: Craniofacial surgery is the standard of treatment for children with moderate to severe trigonocephaly. However, assessing the risk of suboptimal neurodevelopment and added value of surgery is difficult in individual cases. In this study we aim to address the hypothesis that brain development is restricted in trigonocephaly patients by investigating cerebral blood flow in the frontal lobe. Methods: Between 2018 and 2020, we prospectively included trigonocephaly patients for whom a surgical correction was considered in an MRI study measuring cerebral perfusion with arterial spin labeling (ASL). The mean value of cerebral blood flow (CBF) in the frontal lobe was calculated for each subject and compared between the trigonocephaly patients and healthy controls. Results: MRI scans of 36 trigonocephaly patients (median age 0.5y, IQR 0.3, 11 females) were included and compared with 16 controls without cerebral pathology (median age 0.83y, IQR 0.56, 10 females). The mean CBF values in the frontal lobe of the trigonocephaly patients (73.0 ml/100g/min) did not appear to be significantly different in comparison with controls (70.5 ml/100g/min, p = 0.6479). The superior, middle, and inferior part of the frontal lobe showed no significant differences either. Conclusions: Before surgery, the frontal lobe of trigonocephaly patients aged under 18 months old has a normal CBF. In addition to the previously reported very low prevalence of papilledema or impaired skull growth, this finding further supports our hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. 1 . It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of non-perfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultra-high field ASL. We aim to provide a high level understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics that are outside the scope of this article, and are reviewed at length in separate articles, include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as ‘chemo fog’. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well-established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially allow to take these treatment side-effects into account and pave the way towards a more personalized treatment planning. This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side-effects of cancer therapy in normal-appearing brain tissue. Sixty-six studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The reviewed studies were assessed for risk of bias using a modified QUADAS-2 tool, of which findings were summarized. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research.

Non-invasive measurement of cerebral perfusion is promising for identifying individuals at high risk of cerebrovascular disease for prevention strategies. We tested whether the new and easily calculated arterial spin labelling (ASL) MRI parameter for vascular and tissue signal distribution - ‘spatial coefficient of variation’ (ASL-sCoV) - correlates better as a radiological marker with atherosclerotic risk than the more courant markers white matter hyperintensity volume (WMHV) and cerebral blood flow (CBF). Methods 195 participants of the preDIVA trial, aged 72-80 years with systolic hypertension (>140 mmHg) were invited for 2 MRI-scans 2-3 years apart. WMHV was derived from 3D FLAIR; grey matter CBF and ASL-sCoV from ASL. The ASL-sCoV was defined as the standard deviation of CBF divided by the mean CBF in the entire region of interest. Atherosclerotic risk was operationalized as 10-year cardiovascular risk by the Systematic COronary Risk Evaluation Older Persons (SCORE O.P.) and calculated at baseline and follow-up. Data were analysed using linear regression. Results CBF was associated with atherosclerotic risk scores at baseline (standardized-beta=-0.26, 95%CI=-0.40,-0.13, p<0.001) but not on follow-up (standardized-beta=-0.14, 95%CI=-0.33,0.04, p=0.12). ASL-sCoV was associated with atherosclerotic risk scores at both time points (baseline standardized-beta=0.23, 95%CI=0.10,0.36, p<0.0001, follow-up standardized beta= 0.20, 95%CI=0.03,0.36, p=0.02). WMHV was not significantly associated with atherosclerotic risk scores at either time-points (p>0.25). There were no longitudinal associations between changes in MRI parameters and baseline atherosclerotic risk scores. Imputation of missing values, exclusion of outliers, and repeating analyses using the Framingham- and ASCVD risk scores instead of the SCORE O.P. gave similar results. Conclusions Our findings suggest that ASL-sCoV correlates better with atherosclerotic risk than the more conventional markers CBF and WMH