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Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3.

This study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in participants without or with either heart failure, carotid occlusive disease, or vascular cognitive impairment. Neighbourhood walkability at baseline was positively associated with global cognition and attention-psychomotor speed. These associations were stronger in patients with vascular cognitive impairment. Individuals who live in residential areas with higher walkability levels were less likely to have impairments in language and executive functioning at two-year follow-up. These findings highlight the importance of the built environment for cognitive functioning in healthy and vulnerable groups.

Background: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer’s disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co-morbidity with Alzheimer’s disease. So far, DMVs have not been evaluated in CAA. Objective: To evaluate DMVs in Dutch-type hereditary CAA (D-CAA) mutation carriers and controls, in relation to MRI markers associated with D-CAA. Methods: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density were quantified on 7 Tesla 3D susceptibility weighted MRI in pre-symptomatic D-CAA mutation carriers (n = 8), symptomatic D-CAA mutation carriers (n = 8), and controls (n = 25). Hemorrhagic MRI markers (cerebral microbleeds, intracerebral hemorrhages, cortical superficial siderosis, convexity subarachnoid hemorrhage), non-hemorrhagic MRI markers (white matter hyperintensities, enlarged perivascular spaces, lacunar infarcts, cortical microinfarcts), cortical grey matter perfusion, and diffusion tensor imaging parameters were assessed in D-CAA mutation carriers. Univariate general linear analysis was used to determine associations between DMV parameters and MRI markers. Results: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density did not differ between pre-symptomatic D-CAA mutation carriers, symptomatic D-CAA mutation carriers, and controls. No associations were found between DMV parameters and MRI markers associated with D-CAA. Conclusion: This study indicates that vascular amyloid-β deposition does not affect DMV parameters. In patients with CAA, DMVs do not seem to play a role in the pathogenesis of MRI markers associated with CAA.

Background Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable. Purpose To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue. Study type Prospective. Population Eight breast cancer patients. Field strength/sequence A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout. Assessment VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam. Statistical tests Intra-class correlation coefficient (ICC) for interobserver agreement. Results The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score. Data conclusion We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients. Evidence level 1 TECHNICAL EFFICACY: Stage 1.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive, life-saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined cardiac output and cerebral blood flow in patients undergoing TAVI to test the hypothesis that improved cardiac output after TAVI is associated with an increase in cerebral blood flow. DESIGN: Prospective cohort study. SETTING: European high-volume tertiary multidisciplinary cardiac care. PARTICIPANTS: Thirty-one patients (78.3 ± 4.6 years; 61% female) with severe symptomatic aortic valve stenosis. MEASUREMENTS: Noninvasive prospective assessment of cardiac output (L/min) by inert gas rebreathing and cerebral blood flow of the total gray matter (mL/100 g per min) using arterial spin labeling magnetic resonance imaging in resting state less than 24 hours before TAVI and at 3-month follow-up. Cerebral blood flow change was defined as the difference relative to baseline. RESULTS: On average, cardiac output in patients with severe aortic valve stenosis increased from 4.0 ± 1.1 to 5.4 ± 2.4 L/min after TAVI (P =.003). The increase in cerebral blood flow after TAVI strongly varied between patients (7% ± 24%; P =.41) and related to the increase in cardiac output, with an 8.2% (standard error = 2.3%; P =.003) increase in cerebral blood flow per every additional liter of cardiac output following the TAVI procedure. CONCLUSION: Following TAVI, there was an association of increase in cardiac output with increase in cerebral blood flow. These findings encourage future larger studies to determine the influence of TAVI on cerebral blood flow and cognitive function.

Purpose Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of intravascular from tissue signal. The bipolar gradient technique measures the intravascular fraction by removing flowing spins. The T2 -relaxation-under-spin-tagging (TRUST) technique modulates the TE to differentiate between intravascular and extravascular spins based on T2 . These modules were combined into a single time-encoded pseudo-continuous arterial spin labeling sequence to compare their mechanisms of action as well as their assessment of water transition across the blood-brain barrier. Methods This protocol was acquired on a scanner with 9 healthy volunteers who provided written, informed consent. The sequence consisted of a Hadamard-encoded pseudo-continuous arterial spin labeling module, followed by the TRUST module (effective TEs of 0, 40, and 80 ms) and bipolar flow-crushing gradients (2, 4, and ∞ cm/s). An additional experiment was performed with TRUST and a 3D gradient and spin-echo readout. Results Gradients imperfectly canceled the intravascular signal, as evidenced by the presence of residual signal in the arteries at early postlabeling delays as well as the underestimation of the intravascular fraction as compared with the TRUST method. The TRUST module allowed us to detect the transport of water deeper into the vascular tree through changes in T2 than the used crusher gradients could, with their limited b-value. Conclusion Of the implemented techniques, TRUST allowed us to follow intravascular signal deeper into the vascular tree than the approach with (relatively weak) crusher gradients when quantifying the transport time of water across the blood-brain barrier.

Cerebral vein thrombosis (CVT) is a rare presentation of venous thromboembolism. Prompt and accurate diagnosis is essential as delayed recognition and treatment may lead to permanent disability or even death. Since no validated diagnostic algorithms exist, the diagnosis of CVT mainly relies on neuroimaging. Digital subtraction angiography (DSA) is the historical diagnostic standard for CVT, but is rarely used nowadays and replaced by computed tomography (CT) and magnetic resonance imaging (MRI). High quality studies to evaluate the diagnostic test characteristics of state of the art imaging modalities are however unavailable to date. This review provides an overview of the best available evidence regarding the diagnostic performance of CT and MRI for the diagnosis of CVT. Notably, available studies are observational, mostly small, outdated, and with a high risk of bias. Therefore, direct comparison between studies is difficult due to large diversity in study design, imaging method, reference standard, patient selection and sample size. In general, contrast-enhanced techniques are more accurate for the diagnosis of CVT then non-contrast-enhanced techniques. CT venography and MRI have been both reported to be adequate for establishing a final diagnosis of CVT, but choice of modality as used in clinical practice depends on availability, local preference and experience, as well as patient characteristics. Our review underlines the need for high-quality diagnostic studies comparing CT venography and MRI in specific settings, to improve clinical care and standardize clinical trials.

The Dutch prospective multicenter cohort study COPE (Cognitive decline in Older Patients with End stage renal disease) aimed to investigate the association of cardiovascular structure and function with cerebrovascular changes and cognitive function in 85 older patients with chronic kidney disease stage 4 and 5, awaiting either dialysis or conservative care. MRI was performed measuring aortic stiffness (pulse wave velocity [PWV]) and cardiac systolic function (ejection fraction and cardiac index). Outcomes were MRI-derived cerebrovascular changes (microbleeds, lacunes and white matter hyperintensities) and cognitive function (memory, executive function and psychomotor speed). Mean age was 76 years and 66% were male. No statistically significant associations were observed between cardiovascular parameters and cerebrovascular changes. Cognitive function was worse in patients with high compared to low PWV in all three cognitive domains. Although there were clinically relevant associations of high PWV with poor cognition in all domains, after adjustment for age, sex and education only the Trail Making Test A remained statistically significant (p=0.030). In conclusion, this study suggests that a higher PWV might be associated with lower cognitive function, suggesting that arterial stiffness may be an underlying mechanism of development of cognitive impairment in older patients with ESRD. Larger studies should replicate and extend these findings.

In the 1980's some of the earliest studies of arterial spin labeling (ASL) MRI have demonstrated its ability to generate MR angiography (MRA) images. Thanks to many technical improvements, ASL has been success-fully moving its position from the realm of research into the clinical area, albeit more known as perfusion imaging than as MRA. For MRA imaging, other techniques such as time-of-flight, phase contrast MRA and contrast-enhanced (CE) MRA are more popular choices for clinical applications. In the last decade, however, ASL-MRA has been experiencing a remarkable revival, especially because of its non-invasive nature, i.e. the fact that it does not rely on the use of contrast agent. Very importantly, there are additional benefits of using ASL for MRA. For example, its higher flexibility to achieve both high spatial and temporal resolution than CE dynamic MRA, and the capability of vessel specific visualization, in which the vascular tree arising from a selected artery can be exclusively visualized. In this article, the implementation and recent developments of ASI,-based MRA are discussed; not only focusing on the basic sequences based upon pulsed ASL or pseudo-continuous ASL, but also including more recent labeling approaches, such as vessel-selective labeling, velocity-selective ASL, vessel-encoded ASL and time-encoded ASL. Although these ASL techniques have been already utilized in perfusion imaging and their usefulness has been suggested by many studies, some additional considerations should be made when employing them for MRA, since there is something more than the difference of the spatial resolution of the readout sequence. Moreover, extensive discussion is included on what readout sequence to use, especially by highlighting how to achieve high spatial resolution while keeping scan-time reasonable such that the ASL-MRA sequence can easily be included into a clinical examination.

Background and Purpose: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy–related intracerebral hemorrhage. Methods: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis). Results: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy–related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2–18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1–17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0–8]) patients with deep perforating arteriopathy–related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5–3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6–47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable. Conclusions: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.

Purpose: To develop a method for MR Fingerprinting (MRF) sequence optimization that takes both the applied undersampling pattern and a realistic reference map into account. Methods: A predictive model for the undersampling error leveraging on perturbation theory was exploited to optimize the MRF flip angle sequence for improved robustness against undersampling artifacts. In this framework parameter maps from a previously acquired MRF scan were used as reference. Sequences were optimized for different sequence lengths, smoothness constraints and undersampling factors. Numerical simulations and in vivo measurements in eight healthy subjects were performed to assess the effect of the performed optimization. The optimized MRF sequences were compared to a conventionally shaped flip angle pattern and an optimized pattern based on the Cramér–Rao lower bound (CRB). Results: Numerical simulations and in vivo results demonstrate that the undersampling errors can be suppressed by flip angle optimization. Analysis of the in vivo results show that a sequence optimized for improved robustness against undersampling with a flip angle train of length 400 yielded significantly lower median absolute errors in (Formula presented.) : (Formula presented.) and (Formula presented.) : (Formula presented.) compared to the conventional ((Formula presented.) : (Formula presented.), (Formula presented.) : (Formula presented.)) and CRB-based ((Formula presented.) : (Formula presented.), (Formula presented.) : (Formula presented.)) sequences. Conclusion: The proposed method is able to optimize the MRF flip angle pattern such that significant mitigation of the artifacts from strong k-space undersampling in MRF is achieved.

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R-2((*)) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time-consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R-2((*)) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open-source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient-echo sequence (proof-of-concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient-echo and spin-echo sequences. The results show that for both gradient-echo and spin-echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R-2((*)) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.

The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, ‘uncorrected’, images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.

Purpose Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo, while mitigating the MTC. Methods VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three-pool Lorentzian fitting. Different B-1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates. Results The results show the importance of removing MTC when applying VDMP in vivo and the influence of B-1 for distinguishing different pools. Finally, the optimal B-1 and mixing times to effectively saturate slow- and fast-exchanging components are also reported. Slow-exchanging amides and rNOE components could be distinguished when using B-1 = 1 mu T and t(mix) = 10 ms and 40 ms, respectively. Fast-exchanging components reached the highest saturation when using a B-1 = 2.8 mu T and t(mix) = 0 ms. Conclusion VDMP is a powerful CEST-editing tool, exploiting chemical exchange-rate differences. After MTC removal, it allows separate assessment of slow- and fast-exchanging solute pools in in vivo human brain.

PURPOSE In this paper, the ability to quantify cerebral blood flow by arterial spin labeling (ASL) was studied by investigating the separation of the macrovascular and tissue component using a 2-component model. Underlying assumptions of this model, especially the inclusion of dispersion in the analysis, were studied, as well as the temporal resolution of the ASL datasets. METHODS Four different datasets were acquired: (1) 4D ASL angiography to characterize the macrovascular component and to study dispersion modeling within this component, (2) high temporal resolution ASL data to investigate the separation of the 2 components and the effect of dispersion modelling on this separation, (3) low temporal resolution ASL dataset to study the effect of the temporal resolution on the separation of the 2 components, and (4) low temporal resolution ASL data with vascular crushing. RESULTS The model that included a gamma dispersion kernel had the best fit to the 4D ASL angiography. For the high temporal resolution ASL dataset, inclusion of the gamma dispersion kernel led to more signal included in the arterial blood volume map, which resulted in decreased cerebral blood flow values. The arterial blood volume and cerebral blood flow maps showed overall higher arterial blood volume values and lower cerebral blood flow values for the high temporal resolution dataset compared to the low temporal resolution dataset. CONCLUSION Inclusion of a gamma dispersion kernel resulted in better fitting of the model to the data. The separation of the macrovascular and tissue component is affected by the inclusion of a gamma dispersion kernel and the temporal resolution of the ASL dataset.

Purpose To develop a new water-fat separation and B-0 estimation algorithm to effectively suppress the multiple resonances of fat signal in EPI. This is especially relevant for DWI where fat is often a confounding factor. Methods Water-fat separation based on chemical-shift encoding enables robust fat suppression in routine MRI. However, for EPI the different chemical-shift displacements of the multiple fat resonances along the phase-encoding direction can be problematic for conventional separation algorithms. This work proposes a suitable model approximation for EPI under B-0 and fat off-resonance effects, providing a feasible multi-peak water-fat separation algorithm. Simulations were performed to validate the algorithm. In vivo validation was performed in 6 volunteers, acquiring spin-echo EPI images in the leg (B-0 homogeneous) and head-neck (B-0 inhomogeneous) regions, using a TE-shifted interleaved EPI sequence with/without diffusion sensitization. The results are numerically and statistically compared with voxel-independent water-fat separation and fat saturation techniques to demonstrate the performance of the proposed algorithm. Results The reference separation algorithm without the proposed spatial shift correction caused water-fat ambiguities in simulations and in vivo experiments. Some spectrally selective fat saturation approaches also failed to suppress fat in regions with severe B-0 inhomogeneities. The proposed algorithm was able to achieve improved fat suppression for DWI data and ADC maps in the head-neck and leg regions. Conclusion The proposed algorithm shows improved suppression of the multi-peak fat components in multi-shot interleaved EPI applications compared to the conventional fat saturation approaches and separation algorithms.

PurposeTo study placental function—both perfusion and an oxygenation surrogate (T*2)—simultaneously and quantitatively in‐vivo.MethodsFifteen pregnant women were scanned on a 3T MR scanner. For perfusion measurements, a velocity selective arterial spin labeling preparation module was placed before a multi‐echo gradient echo EPI readout to integrate T*2 and perfusion measurements in 1 joint perfusion‐oxygenation (PERFOX) acquisition. Joint motion correction and quantification were performed to evaluate changes in T*2 and perfusion over GA.ResultsThe optimized integrated PERFOX protocol and post‐processing allowed successful visualization and quantification of perfusion and T*2 in all subjects. Areas of high T*2 and high perfusion appear to correspond to placental sub‐units and show a systematic offset in location along the maternal‐fetal axis. The areas of highest perfusion are consistently closer to the maternal basal plate and the areas of highest T*2 closer to the fetal chorionic plate. Quantitative results show a strong negative correlation of gestational age with T*2 and weak negative correlation with perfusion.ConclusionsA strength of the joint sequence is that it provides truly simultaneous and co‐registered estimates of local T*2 and perfusion, however, to achieve this, the time per slice is prolonged compared to a perfusion only scan which can potentially limit coverage. The achieved interlocking can be particularly useful when quantifying transient physiological effects such as uterine contractions. PERFOX opens a new avenue to elucidate the relationship between maternal supply and oxygen uptake, both of which are central to placental function and dysfunction.

Purpose Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low‐perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise‐induced perfusion changes in muscle in two distant slices. Methods Label around and between two 7‐cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split‐label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting‐state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single‐slice FAIR as a reference. Results We show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split‐label multislice approach shows good agreement with separate single‐slice FAIR acquisitions in brain, as well as in muscle following exercise. Conclusion Split‐label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice.

Purpose: To monitor the complete passage of the labeled blood through the vascular tree into tissue and improve the quantification of ASL maps, we evaluated the effect of 3D gradient and spin -echo (GRASE) readout segments on temporal SNR (tSNR) and image blurriness for time -encoded pseudo -continuous arterial spin labeling and the effect of flow -compensation gradients on the presence of intravascular signal.Methods: Fifteen volunteers were scanned using time -encoded pCASL with 2D EPI and single -segment, two -segments, and three -segments 3D-GRASE readouts with first -order flow compensation (FC) gradients. Two -segments 3D-GRASE scans were acquired with 25%, 50%, 75%, and 100% of full first -order FC. Temporal SNR was assessed, and cerebral blood flow and arterial blood volume were quantified for all readout strategies.Results: For single -segment 3D GRASE, tSNR was comparable to 2D EPI for perfu sion signal but worse for the arterial signal. Two -segments and three -segments 3D GRASE resulted in higher tSNR than 2D EPI for perfusion and arterial signal. The arterial signal was not well visualized for 3D-GRASE data without. FC. Visualization of the intravascular signal at postlabeling delays of 660 ms and 1060 ms was restored with EC. Adequate visualization of the intravascular signal was achieved from 75% of FC gradient strength at a postlabeling delay of 660 ms. For a postlabeling delay of 1060 ms, full-FC gradients were the best option to depict intravascularConclusion: Segmented GRASE provided higher effective tSNR compared with 2D-EPI and single -segment GRASE. Flow compensation with GRASE readout should be carefully controlled when applying for time -encoded pCASL to visualize intravascular signal.

The objective of the current study was to combine a time‐encoded pseudocontinuous arterial spin labeling (te‐pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset, both in a highly flexible single‐slice approach as well as within a multislice setting. A te‐pCASL preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single‐slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single‐slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase, only the densely sampled center of k‐space was included in the reconstruction. For a multislice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te‐pCASL preparation was used as the only source for dynamic information. The multislice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te‐pCASL preparation with a golden angle radial readout, single‐slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions allows for multislice acquisition., A time‐encoded pseudocontinuous arterial spin labeling scheme was combined with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset. This allows for retrospectively changing the temporal window, because the golden angle readout was optimized as a temporal resolution tool. Optimizing this readout for different spatial resolutions shows the ability to display the inflow of labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage.

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ0-thal), 20 patients with mild SCD (HbSC and HbSβ+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.

Background and Purpose: Cortical calcifications have been reported in patients with cerebral amyloid angiopathy (CAA), although their prevalence and pathophysiology are unknown. We investigated the frequency of calcifications on computed tomography, their association with intracerebral hemorrhage (ICH) and their coexistence with a striped pattern of the occipital cortex reflecting microcalcifications on ultra-high-field 7T-magnetic resonance imaging in Dutch-type hereditary CAA (D-CAA) and sporadic CAA. Methods: We included D-CAA mutation carriers with a proven APP (amyloid precursor protein) mutation or ≥1 lobar ICH and ≥1 first-degree relative with D-CAA and sporadic CAA patients with probable CAA according to the modified Boston criteria. D-CAA carriers were regarded symptomatic when they had a history of symptomatic ICH. We assessed the presence, location, and progression of calcifications and their association with ICH and the striped occipital cortex. Results: We found cortical calcifications in 15/81 (19% [95% CI, 11–29]) D-CAA mutation carriers (15/69 symptomatic and 0/12 presymptomatic) and in 1/59 (2% [95% CI, 0–9]) sporadic CAA patients. Calcifications were all bilateral located in the occipital lobes. In 3/15 (20%) of the symptomatic D-CAA patients the calcifications progressed over a period up to 10 years. There was evidence of an association between cortical calcifications and new ICH development (hazard ratio, 7.1 [95% CI, 0.9–54.9], log-rank P =0.03). In 7/25 D-CAA symptomatic carriers in whom a 7T-magnetic resonance imaging was performed, a striped pattern of the occipital cortex was present; in 3/3 (100%) of those with calcifications on computed tomography and 4/22 (18%) of those without calcifications. Conclusions: Occipital cortical calcifications are frequent in D-CAA but seem to be rare in sporadic CAA. Their absence in presymptomatic carriers and their association with ICH might suggest that they are a marker for advanced CAA. Cortical calcifications on computed tomography seem to be associated with the striped occipital cortex on 7T-magnetic resonance imaging which may possibly represent an early stage of calcification.

International audience; Impaired cerebrovascular function is an early biomarker for cerebral amyloid angiopathy (CAA), a neurovascular disease leading to stroke and dementia. The transgenic Swedish Dutch Iowa (Tg-SwDI) mouse model is a model for microvascular CAA, but the extent to which the model reflects similar impairments in cerebrovascular function is not yet fully understood. We used arterial spin labeling (ASL)-MRI and laser Doppler flowmetry (LDF) for extensive functional assessment of the Tg-SwDI brain vasculature using a longitudinal study design. Mice were followed-up until 1 year of age, when extensive amyloid-✂ pathology was visible. Unexpectedly, baseline cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to a hypercapnia challenge in Tg-SwDI mice showed similar estimates as age-matched wild type control mice. The preserved vascular function was found irrespective of the anesthesia protocol applied, i.e., isoflurane or a combination of urethane and-chloralose. Changes in CBF and CVR were however observed as an effect of age and anesthesia. Our findings contradict earlier results obtained in the same mouse model and question to what extent microvascular CAA as seen in Tg-SwDI mice is representative for cerebrovascular dysfunction observed in CAA patients.

Purpose: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). Methods: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. Results: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P .05) with good correlations on subject level. Conclusion: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR.

Background: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function. Objective: To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function. Methods: 160 outpatient clinic patients (68.8±8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker). Results: Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05). Conclusion: Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns.

Purpose Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]). Methods Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney). Results In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B1 -inhomogeneity. All ASL techniques were relatively robust to respiratory motion. Conclusion In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B1 -sensitivity of VSI-ASL is necessary to match the performance of FAIR.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners.The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice.ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow.ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P

Background The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT). Methods The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed. Results The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed. Conclusion Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.

Purpose Arterial transit time uncertainties and challenges during planning are potential issues for renal perfusion measurement using spatially selective arterial spin labeling techniques. To mitigate these potential issues, a spatially non-selective technique, such as velocity-selective arterial spin labeling (VSASL), could be an alternative. This article explores the influence of VSASL sequence parameters and respiratory induced motion on VS-label generation. Methods VSASL data were acquired in human subjects (n= 15), with both single and dual labeling, during paced-breathing, while essential sequence parameters were systematically varied; (1) cutoff velocity, (2) labeling gradient orientation and (3) post-labeling delay (PLD). Pseudo-continuous ASL was acquired as a spatially selective reference. In an additional free-breathing single VSASL experiment (n= 9) we investigated respiratory motion influence on VS-labeling. Absolute renal blood flow (RBF), perfusion weighted signal (PWS), and temporal signal-to-noise ratio (tSNR) were determined. Results (1) With decreasing cutoff velocity, tSNR and PWS increased. However, undesired tissue labeling occurred at low cutoff velocities (

Purpose: Placental function is key for successful human pregnancies. Perfusion may be a sensitive marker for the in vivo assessment of placental function. Arterial spin labeling (ASL) MRI enables noninvasive measurement of tissue perfusion and it was recently suggested that ASL with velocity-selective (VS) labeling could be advantageous in the placenta. We systematically evaluated essential VS-ASL sequence parameters to determine optimal settings for efficient placental perfusion measurements.Methods: Eleven pregnant women were scanned at 3T using VS-ASL with 2D multislice echo planar imaging (EPI)-readout. One reference VS-ASL scan was acquired in all subjects; within subgroups the following parameters were systematically varied: cutoff velocity, velocity encoding direction, and inflow time. Visual evaluation and region of interest analyses were performed to compare perfusion signal differences between acquisitions.Results: In all subjects, a perfusion pattern with clear hyperintense focal regions was observed. Perfusion signal decreased with inflow time and cutoff velocity. Subject-specific dependence on velocity encoding direction was observed. High temporal signal-to-noise ratios with high contrast on the perfusion images between the hyperintense regions and placental tissue were seen at similar to 1.6 cm/s cutoff velocity and similar to 1000 ms inflow time. Evaluation of measurements at multiple inflow times revealed differences in blood flow dynamics between placental regions.Conclusion: Placental perfusion measurements are feasible at 3T using VS-ASL with 2D multislice EPI-readout. A clear dependence of perfusion signal on VS labeling parameters and inflow time was demonstrated. Whereas multiple parameter combinations may advance the interpretation of placental circulation dynamics, this study provides a basis to select an effective set of parameters for the observation of placenta perfusion natural history and its potential pathological changes.

Purpose: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was investigated.Methods: A short-PLD sequence was developed where a single VSASL- or AccASL-module was preceded by pCASL labeling to isolate the arterial blood pool. ASL subtraction was performed with label/control images with similar cardiac phase and time-of-measurement, followed by retrospective binning in 10 cardiac phase bins. ASL signal variation over the heart cycle was evaluated and tested for significance using a permutation test.Results: VSASL and AccASL showed significant arterial signal fluctuations over the cardiac cycle of up to similar to 36% and similar to 64%, respectively, mainly in areas containing large arteries. pCASL also showed significant signal fluctuations, of up to similar to 25% in arteries. Raw label/control images confirmed that the observed signal fluctuations were caused by the amount of label produced during the cardiac cycle, rather than inflow-effects, because the raw images did not all show equal cardiac phase dependence. No significant effects of the cardiac cycle were found on the gray matter ASL-signal.Conclusion: Significant influence of the cardiac cycle on the generated label was found for spatially nonselective ASL-sequences. Hence, to become independent of the cardiac cycle, sufficient averages need to be taken. Alternatively, these findings could be highly interesting for the purpose of quantifying pulsatility more distally in the vascular tree.

Adaptive intelligence aims at empowering machine learning techniques with the additional use of domain knowledge. In this work, we present the application of adaptive intelligence to accelerate MR acquisition. Starting from undersampled k-space data, an iterative learning-based reconstruction scheme inspired by compressed sensing theory is used to reconstruct the images. We developed a novel deep neural network to refine and correct prior reconstruction assumptions given the training data. The network was trained and tested on a knee MRI dataset from the 2019 fastMRI challenge organized by Facebook AI Research and NYU Langone Health. All submissions to the challenge were initially ranked based on similarity with a known groundtruth, after which the top 4 submissions were evaluated radiologically. Our method was evaluated by the fastMRI organizers on an independent challenge dataset. It ranked #1, shared #1, and #3 on respectively the $8\times $ accelerated multi-coil, the $4\times $ multi-coil, and the $4\times $ single-coil tracks. This demonstrates the superior performance and wide applicability of the method.

Introduction: We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]).Methods: We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains.Results: CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning.Discussion: We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart-brain axis.