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.

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.

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.

Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood-brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD. In this study, a case-control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively. Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P < 0.007). In the CADASIL group, decreased kw in the whole brain (ß = -0.634, P = 0.001), normal-appearing white matter (ß = -0.599, P = 0.002) and temporal lobe (ß = -0.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (ß = 0.458, P = 0.001; ß = 0.884, P = 0.008). This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients, suggesting a common pathophysiological mechanism underlying the two types of hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation-related CSVD, a possibility which should be tested in future research.

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.

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-based local SAR prediction using B1 maps and structural MRI of the head for parallel transmission at 7 T.

PURPOSE: To predict subject-specific local specific absorption rate (SAR) distributions of the human head for parallel transmission (pTx) systems at 7 T. THEORY AND METHODS: Electromagnetic energy deposition in tissues is nonuniform at 7 T, and interference patterns due to individual channels of pTx systems may result in increased local SAR values, which can only be estimated with very high safety margins. We proposed, designed, and demonstrated a multichannel 3D convolutional neural network (CNN) architecture to predict local SAR maps as well as peak-spatial SAR (ps-SAR) levels. We hypothesized that utilizing a three-channel 3D CNN, in which each channel is fed by a B 1 + $$ {B}_1^{+} $$ map, a phase-reversed B 1 + $$ {B}_1^{+} $$ map, and an MR image, would improve prediction accuracies and decrease uncertainties in the predictions. We generated 10 new head-neck body models, along with 389 3D pTx MRI data having different RF shim settings, with their B1 and local SAR maps to support efforts in this field. RESULTS: The proposed three-channel 3D CNN predicted ps-SAR10g levels with an average overestimation error of 20%, which was better than the virtual observation points-based estimation error (i.e., 152% average overestimation). The proposed method decreased prediction uncertainties over 20% (i.e., 22.5%-17.7%) compared to other methods. A safety factor of 1.20 would be enough to avoid underestimations for the dataset generated in this work. CONCLUSION: Multichannel 3D CNN networks can be promising in predicting local SAR values and perform predictions within a second, making them clinically useful as an alternative to virtual observation points-based methods.

Quantification of blood-brain barrier water exchange and permeability with multidelay diffusion-weighted pseudo-continuous arterial spin labeling.

PURPOSE: To present a pulse sequence and mathematical models for quantification of blood-brain barrier water exchange and permeability. METHODS: Motion-compensated diffusion-weighted (MCDW) gradient-and-spin echo (GRASE) pseudo-continuous arterial spin labeling (pCASL) sequence was proposed to acquire intravascular/extravascular perfusion signals from five postlabeling delays (PLDs, 1590-2790 ms). Experiments were performed on 11 healthy subjects at 3 T. A comprehensive set of perfusion and permeability parameters including cerebral blood flow (CBF), capillary transit time (τc ), and water exchange rate (kw ) were quantified, and permeability surface area product (PSw ), total extraction fraction (Ew ), and capillary volume (Vc ) were derived simultaneously by a three-compartment single-pass approximation (SPA) model on group-averaged data. With information (i.e., Vc and τc ) obtained from three-compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual kw quantification, and Ew and PSw can be estimated from long PLD (2490/2790 ms) signals. MCDW-pCASL was compared with a previously developed diffusion-prepared (DP) pCASL sequence, which calculates kw by a two-compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements. RESULTS: Using three-compartment SPA modeling, group-averaged CBF = 51.5/36.8 ml/100 g/min, kw = 126.3/106.7 min-1 , PSw = 151.6/93.8 ml/100 g/min, Ew = 94.7/92.2%, τc = 1409.2/1431.8 ms, and Vc = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW-pCASL perfusion signals increased 3-fold, and individual kw maps calculated by the LRL method achieved higher spatial resolution (3.5 mm3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm3 ). CONCLUSION: MCDW-pCASL allows visualization of intravascular/extravascular ASL signals across multiple PLDs. The three-compartment SPA model provides a comprehensive measurement of blood-brain barrier water dynamics from group-averaged data, and a simplified LRL method was proposed for individual kw quantification.

Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.

This 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 ASL consensus paper. Although 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 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, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. 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.

Diffusion prepared pseudo-continuous arterial spin labeling reveals blood-brain barrier dysfunction in patients with CADASIL.

OBJECTIVES: Diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of the blood-brain barrier (BBB). We aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and to analyze the association between the BBB water exchange rate and MRI/clinical features of these patients. METHODS: Forty-one patients with CADASIL and thirty-six age- and sex-matched controls were scanned with DP-pCASL MRI to estimate the BBB water exchange rate (kw). The MRI lesion burden, the modified Rankin scale (mRS), and the neuropsychological scales were also examined. The association between kw and MRI/clinical features was analyzed. RESULTS: Compared with that in the controls, kw in patients with CADASIL was decreased at normal-appearing white matter (NAWM) (t = - 4.742, p < 0.001), cortical gray matter (t = - 5.137, p < 0.001), and deep gray matter (t = - 3.552, p = 0.001). After adjustment for age, gender, and arterial transit time, kw at NAWM was negatively associated with the volume of white matter hyperintensities (ß = - 0.754, p = 0.001), whereas decreased kw at NAWM was independently associated with an increased risk of abnormal mRS scale (OR = 1.058, 95% CI: 1.013-1.106, p = 0.011) in these patients. CONCLUSIONS: This study found that the BBB water exchange rate was decreased in patients with CADASIL. The decreased BBB water exchange rate was associated with an increased MRI lesion burden and functional dependence of the patients, suggesting the involvement of BBB dysfunction in the pathogenesis of CADASIL. CLINICAL RELEVANCE STATEMENT: DP-pCASL reveals BBB dysfunction in patients with CADASIL. The decreased BBB water exchange rate is associated with MRI lesion burden and functional dependence, indicating the potential of DP-pCASL as an evaluation method for disease severity. KEY POINTS: • DP-pCASL reveals blood-brain barrier dysfunction in patients with CADASIL. • Decreased BBB water exchange rate, an indicator of BBB dysfunction detected by DP-pCASL, was associated with MRI/clinical features of patients with CADASIL. • DP-pCASL can be used as an evaluation method to assess the severity of disease in patients with CADASIL.

Modulation of brain networks during MR-compatible transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

BACKGROUND: Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR. METHODS: Independently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales. RESULTS: Thirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia. DISCUSSION: Perivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity.

Regional homogeneity (ReHo) is a measure of local functional brain connectivity that has been reported to be altered in a wide range of neuropsychiatric disorders. Computed from brain resting-state functional MRI time series, ReHo is also sensitive to fluctuations in cerebral blood flow (CBF) that in turn may be influenced by cerebrovascular health. We accessed cerebrovascular health with Framingham cardiovascular risk score (FCVRS). We hypothesize that ReHo signal may be influenced by regional CBF; and that these associations can be summarized as FCVRS→CBF→ReHo. We used three independent samples to test this hypothesis. A test-retest sample of N = 30 healthy volunteers was used for test-retest evaluation of CBF effects on ReHo. Amish Connectome Project (ACP) sample (N = 204, healthy individuals) was used to evaluate association between FCVRS and ReHo and testing if the association diminishes given CBF. The UKBB sample (N = 6,285, healthy participants) was used to replicate the effects of FCVRS on ReHo. We observed strong CBF→ReHo links (p<2.5 × 10-3) using a three-point longitudinal sample. In ACP sample, marginal and partial correlations analyses demonstrated that both CBF and FCVRS were significantly correlated with the whole-brain average (p<10-6) and regional ReHo values, with the strongest correlations observed in frontal, parietal, and temporal areas. Yet, the association between ReHo and FCVRS became insignificant once the effect of CBF was accounted for. In contrast, CBF→ReHo remained significantly linked after adjusting for FCVRS and demographic covariates (p<10-6). Analysis in N = 6,285 replicated the FCVRS→ReHo effect (p = 2.7 × 10-27). In summary, ReHo alterations in health and neuropsychiatric illnesses may be partially driven by region-specific variability in CBF, which is, in turn, influenced by cardiovascular factors.

Optimization of pseudo-continuous arterial spin labeling at 7T with parallel transmission B1 shimming.

PURPOSE: To optimize pseudo-continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 ( B1+ ) shimming. METHODS: pCASL parameters were optimized based on B1+/B0 field distributions at 7 T with simulation. To increase labeling efficiency, the B1+ amplitude at inflowing arteries was increased with parallel RF transmission B1+ shimming. The "indv-shim" with shimming weights calculated for each individual subject, and the "univ-shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B1+ shimming modes (indv-shim, univ-shim, and CP-shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B1+ amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. RESULTS: The optimal pCASL parameter set (RF duration/gap = 300/250 us, Gave=0.6mT/m,gRatio=10 ) achieved robust perfusion measurement in the presence of B1+/B0 inhomogeneities. Both indv-shim and univ-shim significantly increased B1+ amplitude compared with CP-shim in simulation and in vivo experiment (P < .01). Compared with CP-shim, perfusion signal was increased by 9.5% with indv-shim (P < .05) and by 5.3% with univ-shim (P = .35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. CONCLUSION: The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv-shim and univ-shim further increased labeling efficiency.

Multi-echo balanced SSFP with a sequential phase-encoding order for functional MR imaging at 7T.

PURPOSE: To develop a 2D multi-echo passband balanced SSFP (bSSFP) sequence using an echo-train readout with a sequential phase-encoding order (sequential multi-echo bSSFP), and evaluate its performance in fast functional brain imaging at 7 T. METHODS: As images of sequential multi-echo bSSFP exhibit multiple ghosts due to periodic k-space modulations, a GRAPPA-based reconstruction method was proposed to eliminate ghosting artifacts. MRI experiments were performed to compare the image quality of multi-echo bSSFP and conventional single-echo bSSFP. Submillimeter-resolution fMRI using a checkerboard visual stimulus was conducted to compare the activation characteristics of multi-echo bSSFP, conventional single-echo bSSFP and standard gradient-echo EPI (GE-EPI). RESULTS: A higher mean structural similarity index was found between images of single-echo bSSFP and multi-echo bSSFP with a shorter echo train length (ETL). Multi-echo bSSFP (ETL = 3) showed higher temporal SNR (tSNR) values than GRAPPA-accelerated single-echo bSSFP (R = 2). In submillimeter-resolution fMRI experiments, multi-echo bSSFP (ETL = 3) approached the imaging speed of GRAPPA-accelerated single-echo bSSFP (R = 2), but without tSNR penalty and reduced activation due to acceleration. The median t-value and the number of significantly activated voxels were comparable between GE-EPI and multi-echo bSSFP (ETL = 3) that provides virtually distortion-free functional images and inherits the activation patterns of conventional bSSFP. CONCLUSION: Sequential multi-echo bSSFP (ETL = 3) is suitable for fast fMRI with submillimeter in-plane resolution, and offers an option to accelerate bSSFP imaging without tSNR penalty like parallel imaging.

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla.

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling (pCASL) technique at 7T that offers the capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 ms shorter than in middle/deep layers revealing the time course of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge.

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate the reliability of CO2-CVR quantification in three studies. First, the inter-rater reliability of CO2-CVR data processing was evaluated by having raters from 5 MarkVCID sites process the same 30 CVR datasets using a cloud-based CVR data processing pipeline. Second, the inter-scanner reproducibility of CO2-CVR quantification was assessed in 10 young subjects across two scanners of different vendors. Third, test-retest repeatability was evaluated in 20 elderly subjects from 4 sites with a scan interval of less than 2 weeks. In all studies, the CO2 CVR measurements were performed using the fixed inspiration method, where the subjects wore a nose clip and a mouthpiece and breathed room air and 5% CO2 air contained in a Douglas bag alternatively through their mouth. The results showed that the inter-rater CoV of CVR processing was 0.08 ± 0.08% for whole-brain CVR values and ranged from 0.16% to 0.88% in major brain regions, with ICC of absolute agreement above 0.9959 for all brain regions. Inter-scanner CoV was found to be 6.90 ± 5.08% for whole-brain CVR values, and ranged from 4.69% to 12.71% in major brain regions, which are comparable to intra-session CoVs obtained from the same scanners on the same day. ICC of consistency between the two scanners was 0.8498 for whole-brain CVR and ranged from 0.8052 to 0.9185 across major brain regions. In the test-retest evaluation, test-retest CoV across different days was found to be 18.29 ± 17.12% for whole-brain CVR values, and ranged from 16.58% to 19.52% in major brain regions, with ICC of absolute agreement ranged from 0.6480 to 0.7785. These results demonstrated good inter-rater, inter-scanner, and test-retest reliability in healthy volunteers, and suggested that CO2-CVR has suitable instrumental properties for use as an imaging biomarker of cerebrovascular function in multi-site and longitudinal observational studies and clinical trials.

Optimization of adiabatic pulses for pulsed arterial spin labeling at 7 tesla: Comparison with pseudo-continuous arterial spin labeling.

PURPOSE: To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla. METHODS: Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated. RESULTS: Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest B1+ amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate. CONCLUSION: Optimized wideband uniform rate smooth truncation pulse with the highest B1+ amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling.

Semiautomatic cerebrovascular territory mapping based on dynamic ASL MR angiography without vessel-encoded labeling.

PURPOSE: Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time-resolved 4D magnetic resonance angiography (MRA). METHODS: Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA-derived arterial arrival time maps of intracranial vessels. RESULTS: Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA-based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. CONCLUSION: The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user-defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies.

Assessment of carotid stiffness by measuring carotid pulse wave velocity using a single-slice oblique-sagittal phase-contrast MRI.

PURPOSE: Increased arterial stiffness has been shown to be one of the earliest markers of cerebrovascular dysfunction. As a surrogate marker of arterial stiffness, pulse wave velocity (PWV) quantifications are generally carried out on central and peripheral arteries. The purpose of this study was to develop and evaluate an MRI approach to assess carotid stiffness by measuring carotid PWV (cPWV) using a fast oblique-sagittal phase-contrast MRI sequence. METHODS: In 29 volunteers, a single-slice oblique-sagittal phase-contrast MRI sequence with retrospective cardiac gating was used to quantify blood velocity waveforms along a vessel segment covering the common carotid artery (CCA) and the internal carotid artery (ICA). The CCA-ICA segment length was measured from a region of interest selected on the magnitude image. Phase-contrast MRI-measured velocities were also used to quantify the ICA pulsatility index along with cPWV quantification. RESULTS: The mean value of cPWV calculated using the middle upslope area algorithm was 2.86 ± 0.71 and 3.97 ± 1.14 m/s in young and elderly subjects, respectively. Oblique-sagittal phase-contrast MRI-derived cPWV measurements showed excellent intrascan and interscan repeatability. cPWV and ICA pulsatility index were significantly greater in older subjects compared to those in the young subjects (P < .01 and P = .01, respectively). Also, increased cPWV values were associated with elevated systolic blood pressure (ß = 0.05, P = .03). CONCLUSION: This study demonstrated that oblique-sagittal phase-contrast MRI is a feasible technique for the quantification of both cPWV and ICA pulsatility index and showed their potential utility in evaluating cerebroarterial aging and age-related neurovascular disorders.