Search

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. METHODS: We included Dutch‐type hereditary CAA (D‐CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age‐matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI‐cSVD burden and cognition. RESULTS: D‐CAA ICH− mutation carriers exhibited poorer global cognition and executive function compared to age‐matched controls. Patients with sCAA performed worse across all cognitive domains compared to D‐CAA ICH+ mutation carriers and age‐matched controls. MRI‐cSVD burden is associated with decreased processing speed. DISCUSSION: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI‐cSVD burden being associated with slower processing speed. Highlights: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH).Presymptomatic Dutch‐type CAA (D‐CAA) mutation carriers show worse cognition than age‐matched controls.More early awareness of cognitive dysfunction in CAA before first sICH is needed.Increased cerebral small vessel disease CAA‐burden on magnetic resonance imaging is linked to a decrease in processing speed. [ABSTRACT FROM AUTHOR]

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL‐MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL‐MRI and DSC‐MRI scans were acquired at 3 months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL‐MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow‐up until 9 months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL‐MRI and DSC‐MRI was observed only for ASL images with moderate ATT severity (30%–65%). The perfusion assessment showed ASL‐MRI tending more towards hyperperfusion than DSC‐MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL‐MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p = 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL‐MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium‐based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme – Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast‐enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF. [ABSTRACT FROM AUTHOR]

Non-invasive perfusion imaging by Arterial spin labeling (ASL) can be advantageous at Ultra-high field (UHF) MRI, since the image SNR and the T1 relaxation time both increase with the static field. However, ASL implementation, especially at 7T, is not trivial. Especially for ASL, UHF MRI comes with many challenges, mainly due to B1+ inhomogeneities. This study aimed to investigate the effects of different transmit coil configurations on perfusion-weighted imaging at 7T using a flow-sensitive alternating inversion recovery (FAIR) technique with time-resolved frequency offset corrected inversion (TR-FOCI) pulses for labeling and background suppression. We conducted a performance comparison between a parallel transmit (pTx) system equipped with 32 receive (Rx) and 8 transmit (Tx) channels and a standard setup with 32Rx and 2Tx channels. Our findings demonstrate that the pTx system, characterized by a more homogeneous B1 transmit field, resulted in a significantly higher contrast-to-noise ratio, temporal signal-to-noise ratio, and lower coefficient of variance (CoV) than the standard 2Tx setup. Additionally, both setups demonstrated comparable capabilities for functional mapping of the hand region in the motor cortex, achieving reliable results within a short acquisition time of approximately 5 minutes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time‐encoded arterial spin labeling (te‐ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. METHODS: We compared te‐ASL with single‐postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aβ) negative (−), CU Aβ positive (+), and CI Aβ+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. RESULTS: te‐ASL was more sensitive at detecting CBF reduction in the CU Aβ+ and CI Aβ+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aβ, tau, synaptic dysfunction, and neurodegeneration. DISCUSSION: CBF reduction occurs early in the AD continuum. te‐ASL is more sensitive than single‐PLD ASL at detecting CBF changes in AD. Highlights: Lower CBF can be detected in CU subjects in the early AD continuum.te‐ASL is more sensitive than single‐PLD ASL at detecting CBF alterations in AD.CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is a barrier protecting the brain and a milieu of continuous exchanges between blood and brain. There is emerging evidence that the BBB plays a major role in epileptogenesis and drug‐resistant epilepsy, through several mechanisms, such as water homeostasis dysregulation, overexpression of drug transporters, and inflammation. Studies have shown abnormal water homeostasis in epileptic tissue and altered aquaporin‐4 water channel expression in animal epilepsy models. This review focuses on abnormal water exchange in epilepsy and describes recent non‐invasive MRI methods of quantifying water exchange. Plain Language Summary: Abnormal exchange between blood and brain contribute to seizures and epilepsy. The authors describe why correct water balance is necessary for healthy brain functioning and how it is impacted in epilepsy. This review also presents recent MRI methods to measure water exchange in human brain. These measures would improve our understanding of factors leading to seizures. [ABSTRACT FROM AUTHOR]

The brain's network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer's disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid β—a key culprit in CAA—from the brain to draining lymphatics and systemic circulation remains poorly understood. This knowledge gap is critically important to bridge for understanding the pathophysiology of CAA and accelerate development of targeted therapeutics. The authors of this review recently converged their diverse expertise in the field of perivascular physiology to specifically address this problem within the framework of a Leducq Foundation Transatlantic Network of Excellence on Brain Clearance. This review discusses the overarching goal of the consortium and explores the evidence supporting or refuting the role of impaired perivascular clearance in the pathophysiology of CAA with a focus on translating observations from rodents to humans. We also discuss the anatomical features of perivascular channels as well as the biophysical characteristics of fluid and solute transport. [ABSTRACT FROM AUTHOR]

Metabolite‐weighted chemical exchange saturation transfer MRI can be used to indirectly image metabolites such as creatine and glutamate. This study aims to further explore the contrast of CEST at 2 ppm in the human brain at 7T and investigate the metabolite correlates of CEST at 2 ppm via correlations with magnetic resonance spectroscopy (MRS). Simulations were performed to establish the optimal acquisition parameters, such as total saturation time (tsat) and B1 root mean squared (B1rms) for CEST at 2 ppm in the human brain. Parameters were validated via in vitro phantom studies at 7T using concentrations, pH and temperature comparable to what is found in the human brain. Finally, 10 healthy volunteers were scanned at 7T for comparison with MRS. Our results show that the optimal parameters to acquire CEST at 2 ppm images are: B1rms = 2.14 μT & tsat = 1500 ms, respectively. Comparison with MRS showed no significant correlation between CEST at 2 ppm and total Creatine measured by MRS (R = 0.19; p‐value = 0.273). However, a significant correlation was found between CEST at 2 ppm and Glu (R = 0.39; p‐value = 0.033), indicating the broad Glutamate‐weighted CEST as the main measurable contributor to CEST at 2 ppm. We identified and confirmed optimal CEST at 2 ppm sequence parameters and validated CEST at 2 ppm measurements in a controlled in vitro environment. Our findings suggest that glutamate is a substantial contributor to the CEST at 2 ppm contrast observed in the human brain, whereas the creatine contribution to CEST at 2 ppm in the brain did not show a measurable contribution. [ABSTRACT FROM AUTHOR]

Background: Magnetic Resonance acquisition is a time consuming process, making it susceptible to patient motion during scanning. Even motion in the order of a millimeter can introduce severe blurring and ghosting artifacts, potentially necessitating re‐acquisition. Magnetic Resonance Imaging (MRI) can be accelerated by acquiring only a fraction of k‐space, combined with advanced reconstruction techniques leveraging coil sensitivity profiles and prior knowledge. Artificial intelligence (AI)‐based reconstruction techniques have recently been popularized, but generally assume an ideal setting without intra‐scan motion. Purpose: To retrospectively detect and quantify the severity of motion artifacts in undersampled MRI data. This may prove valuable as a safety mechanism for AI‐based approaches, provide useful information to the reconstruction method, or prompt for re‐acquisition while the patient is still in the scanner. Methods: We developed a deep learning approach that detects and quantifies motion artifacts in undersampled brain MRI. We demonstrate that synthetically motion‐corrupted data can be leveraged to train the convolutional neural network (CNN)‐based motion artifact estimator, generalizing well to real‐world data. Additionally, we leverage the motion artifact estimator by using it as a selector for a motion‐robust reconstruction model in case a considerable amount of motion was detected, and a high data consistency model otherwise. Results: Training and validation were performed on 4387 and 1304 synthetically motion‐corrupted images and their uncorrupted counterparts, respectively. Testing was performed on undersampled in vivo motion‐corrupted data from 28 volunteers, where our model distinguished head motion from motion‐free scans with 91% and 96% accuracy when trained on synthetic and on real data, respectively. It predicted a manually defined quality label ('Good', 'Medium' or 'Bad' quality) correctly in 76% and 85% of the time when trained on synthetic and real data, respectively. When used as a selector it selected the appropriate reconstruction network 93% of the time, achieving near optimal SSIM values. Conclusions: The proposed method quantified motion artifact severity in undersampled MRI data with high accuracy, enabling real‐time motion artifact detection that can help improve the safety and quality of AI‐based reconstructions. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers as they do not require a procedure as invasive as a lumbar puncture. This article aimed to provide an overview of the present clinical data concerning fluid biomarkers associated with CAA and point out the direction of future studies. Among all the biomarkers discussed, amyloid β, neurofilament light chain, matrix metalloproteinases, complement 3, uric acid, and lactadherin demonstrated the most promising evidence. However, the field of fluid biomarkers for CAA is an under-researched area, and in most cases, there are only one or two studies on each of the biomarkers mentioned in this review. Additionally, a small sample size is a common limitation of the discussed studies. Hence, it is hard to reach a solid conclusion on the clinical significance of each biomarker at different stages of the disease or in various subpopulations of CAA. In order to overcome this issue, larger longitudinal and multicentered studies are needed. [ABSTRACT FROM AUTHOR]

Purpose: Multi‐shot diffusion‐weighted EPI allows an increase in image resolution and reduced geometric distortions and can be combined with chemical‐shift encoding (Dixon) to separate water/fat signals. However, such approaches suffer from physiological motion‐induced shot‐to‐shot phase variations. In this work, a structured low‐rank‐based navigator‐free algorithm is proposed to address the challenge of simultaneously separating water/fat signals and correcting for physiological motion‐induced shot‐to‐shot phase variations in multi‐shot EPI‐based diffusion‐weighted MRI. Theory and Methods: We propose an iterative, model‐based reconstruction pipeline that applies structured low‐rank regularization to estimate and eliminate the shot‐to‐shot phase variations in a data‐driven way, while separating water/fat images. The algorithm is tested in different anatomies, including head–neck, knee, brain, and prostate. The performance is validated in simulations and in‐vivo experiments in comparison to existing approaches. Results: In‐vivo experiments and simulations demonstrated the effectiveness of the proposed algorithm compared to extra‐navigated and an alternative self‐navigation approach. The proposed algorithm demonstrates the capability to reconstruct in the multi‐shot/Dixon hybrid space domain under‐sampled datasets, using the same number of acquired EPI shots compared to conventional fat‐suppression techniques but eliminating fat signals through chemical‐shift encoding. In addition, partial Fourier reconstruction can also be achieved by using the concept of virtual conjugate coils in conjunction with the proposed algorithm. Conclusion: The proposed algorithm effectively eliminates the shot‐to‐shot phase variations and separates water/fat images, making it a promising solution for future DWI on different anatomies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to investigate the association between white matter hyperintensity (WMH) shape and volume and the long‐term dementia risk in community‐dwelling older adults. METHODS: Three thousand seventy‐seven participants (mean age: 75.6 ± 5.2 years) of the Age Gene/Environment Susceptibility (AGES)‐Reykjavik study underwent baseline 1.5T brain magnetic resonance imaging and were followed up for dementia (mean follow‐up: 9.9 ± 2.6 years). RESULTS: More irregular shape of periventricular/confluent WMH (lower solidity (hazard ratio (95% confidence interval) 1.34 (1.17 to 1.52), p <.001) and convexity 1.38 (1.28 to 1.49), p <.001); higher concavity index 1.43 (1.32 to 1.54), p <.001) and fractal dimension 1.45 (1.32 to 1.58), p <.001)), higher total WMH volume (1.68 (1.54 to 1.87), p <.001), higher periventricular/confluent WMH volume (1.71 (1.55 to 1.89), p <.001), and higher deep WMH volume (1.17 (1.08 to 1.27), p <.001) were associated with an increased long‐term dementia risk. DISCUSSION: WMH shape markers may in the future be useful in determining patient prognosis and may aid in patient selection for future preventive treatments in community‐dwelling older adults. [ABSTRACT FROM AUTHOR]

Cerebral vascular reactivity quantified using blood oxygen level‐dependent functional MRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid angiopathy. This work investigates the influence of different postprocessing methods on the outcome of such vascular reactivity measurements. Three methods for defining the region of interest (ROI) over which the reactivity is measured are investigated: structural (transformed V1), functional (template based on the activation of a subset of subjects), and percentile (11.5 cm3 most responding voxels). Evaluation is performed both in a test–retest experiment in healthy volunteers (N = 12), as well as in 27 Dutch‐type cerebral amyloid angiopathy patients and 33 age‐ and sex‐matched control subjects. The results show that the three methods select a different subset of voxels, although all three lead to similar outcome measures in healthy subjects. However, in (severe) pathology, the percentile method leads to higher reactivity measures than the other two, due to circular analysis or "double dipping" by defining a subject‐specific ROI based on the strongest responses within each subject. Furthermore, while different voxels are included in the presence of lesions, this does not necessarily result in different outcome measures. In conclusion, to avoid bias created by the method, either a structural or a functional method is recommended. Both of these methods provide similar reactivity measures, although the functional ROI appears to be less reproducible between studies, because slightly different subsets of voxels were found to be included. On the other hand, the functional method did include fewer lesion voxels than the structural method. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of probable cerebral amyloid angiopathy (CAA) is currently mostly based on characteristics of brain MRI. Blood biomarkers would be a cost-effective, easily accessible diagnostic method that may complement diagnosis by MRI and aid in monitoring disease progression. We studied the diagnostic potential of plasma Aβ38, Aβ40, and Aβ42 in patients with hereditary Dutch-type CAA (D-CAA) and sporadic CAA (sCAA). Methods: All Aβ peptides were quantified in the plasma by immunoassays in a discovery cohort (11 patients with presymptomatic D-CAA and 24 patients with symptomatic D-CAA, and 16 and 24 matched controls, respectively) and an independent validation cohort (54 patients with D-CAA, 26 presymptomatic and 28 symptomatic, and 39 and 46 matched controls, respectively). In addition, peptides were quantified in the plasma in a group of 61 patients with sCAA and 42 matched controls. We compared Aβ peptide levels between patients and controls using linear regression adjusting for age and sex. Results: In the discovery cohort, we found significantly decreased levels of all Aβ peptides in patients with presymptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.009; Aβ42: p < 0.001) and patients with symptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.01; Aβ42: p < 0.001) compared with controls. In contrast, in the validation cohort, plasma Aβ38, Aβ40, and Aβ42 were similar in patients with presymptomatic D-CAA and controls (Aβ38: p = 0.18; Aβ40: p = 0.28; Aβ42: p = 0.63). In patients with symptomatic D-CAA and controls, plasma Aβ38 and Aβ40 were similar (Aβ38: p = 0.14; Aβ40: p = 0.38), whereas plasma Aβ42 was significantly decreased in patients with symptomatic D-CAA (p = 0.033). Plasma Aβ38, Aβ40, and Aβ42 levels were similar in patients with sCAA and controls (Aβ38: p = 0.092; Aβ40: p = 0.64. Aβ42: p = 0.68). Conclusions: Plasma Aβ42 levels, but not plasma Aβ38 and Aβ40, may be used as a biomarker for patients with symptomatic D-CAA. In contrast, plasma Aβ38, Aβ40, and Aβ42 levels do not appear to be applicable as a biomarker in patients with sCAA. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary brain tumors, most commonly gliomas, are devastating diseases which in adults are generally fatal. Vascularization is an important aspect of the biological behavior of gliomas, and determining it is valuable for the optimal timing of treatment. Magnetic resonance imaging (MRI) is an excellent non-invasive diagnostic technique for tissue characterization. In this study, we propose an advanced MRI technique, MR vascular fingerprinting based on the dynamic passage of a contrast agent, to gather quantitative information on the major vascular biomarkers of gliomas within an acceptable scan time. This technique was evaluated in six patients with gliomas, obtaining the vascular parameters that deliver information on the vascularity of the tumor. The vessel parameters quantified using the proposed technique were also compared to those quantified using a conventional vessel size imaging technique. This study will significantly contribute to further advances in functional imaging for gliomas. Characterization of tumor microvasculature is important in tumor assessment and studying treatment response. This is possible by acquiring vascular biomarkers with magnetic resonance imaging (MRI) based on dynamic susceptibility contrast (DSC). We propose magnetic resonance vascular fingerprinting (MRVF) for hybrid echo planar imaging (HEPI) acquired during the first passage of the contrast agent (CA). The proposed approach was evaluated in patients with gliomas, and we simultaneously estimated vessel radius and relative cerebral blood volume. These parameters were also compared to the respective values estimated using the previously introduced vessel size imaging (VSI) technique. The results of both methods were found to be consistent. MRVF was also found to be robust to noise in the estimation of the parameters. DSC-HEPI-based MRVF provides characterization of microvasculature in gliomas with a short acquisition time and can be further improved in several ways to increase our understanding of tumor physiology. [ABSTRACT FROM AUTHOR]

For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF‐ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF‐ASL signal for blood–CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post‐labeling delay (PLD), and an eight‐echo 3D‐GRASE readout. A dataset was simulated to estimate the effect of CSF‐PVC with known ground‐truth parameters. Differences between the results of CSF‐PVC and non‐CSF‐PVC were estimated for regions of interest (ROIs) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC‐CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long‐TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi‐PLD (model fitting) quantification than for single PLD (~1–5% difference). In the choroid plexus, the difference between CSF‐PVC and non‐CSF‐PVC was much larger, averaging around 30%. Long‐TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of spatio‐temporal encoding (SPEN) readout for pseudo‐continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. Methods: A 2D self‐refocused T2*‐compensated hybrid SPEN scheme, with super‐resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp*Tchirp) was varied and, the aneurysm clip‐induced artifact was evaluated in phantom (label‐images) as well as in vivo (perfusion‐weighted signal (PWS)‐maps and temporal SNR (tSNR)). In vivo results were compared to gradient‐echo EPI (GE‐EPI) and spin‐echo EPI (SE‐EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE‐EPI. SPEN with Q ˜ 75 encodes with the same off‐resonance robustness as EPI. Results: The clip‐induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE‐EPI and GE‐EPI in vivo. tSNR decreased with Q and the tSNR of GE‐EPI and SE‐EPI corresponded to SPEN with a Q‐value of approximately ˜85 and ˜108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE‐EPI did not. tSNR remained relatively stable when the time between SPEN‐excitation and start of the next labeling‐module was more than ˜1000 ms. Conclusion: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE‐EPI and GE‐EPI. However, the SPEN chirp‐pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a self‐navigation strategy to improve scan efficiency and image quality of water/fat‐separated, diffusion‐weighted multishot echo‐planar imaging (ms‐EPI). This is accomplished by acquiring chemical shift‐encoded diffusion‐weighted data and using an appropriate water‐fat and diffusion‐encoded signal model to enable reconstruction directly from k‐space data. Multishot EPI provides reduced geometric distortion and improved signal‐to‐noise ratio in diffusion‐weighted imaging compared with single‐shot approaches. Multishot acquisitions require corrections for physiological motion‐induced shot‐to‐shot phase errors using either extra navigators or self‐navigation principles. In addition, proper fat suppression is important, especially in regions with large B0 inhomogeneity. This makes the use of chemical shift encoding attractive. However, when combined with ms‐EPI, shot‐to‐shot phase navigation can be challenging because of the spatial displacement of fat signals along the phase‐encoding direction. In this work, a new model‐based, self‐navigated water/fat separation reconstruction algorithm is proposed. Experiments in legs and in the head–neck region of 10 subjects were performed to validate the algorithm. The results are compared with an image‐based, two‐dimensional (2D) navigated water/fat separation approach for ms‐EPI and with a conventional fat saturation approach. Compared with the 2D navigated method, the use of self‐navigation reduced the shot duration time by 30%–35%. The proposed algorithm provided improved diffusion‐weighted water images in both leg and head–neck regions compared with the 2D navigator‐based approach. The proposed algorithm also produced better fat suppression compared with the conventional fat saturation technique in the B0 inhomogeneous regions. In conclusion, the proposed self‐navigated reconstruction algorithm can produce superior water‐only diffusion‐weighted EPI images with less artefacts compared with the existing methods. [ABSTRACT FROM AUTHOR]

Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin labeling (ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within muscle, whereas recent literature has reported proximodistal differences in oxidative capacity and perfusion. Here, we acquired pulsed ASL data in 12 healthy volunteers after dorsiflexion exercise in two slices separated distally by 7 cm. We combined this with a Look‐Locker scheme to acquire images at multiple postlabeling delays (PLDs) and with a multiecho readout to measure T2*. This enabled the simultaneous evaluation of quantitative muscle blood flow (MBF), arterial transit time (ATT), and T2* relaxation time in the tibialis anterior muscle during recovery. Using repeated measures analyses of variance we tested the effect of time, slice location, and their interaction on MBF, ATT, and T2*. Our results showed a significant difference as a function of time postexercise for all three parameters (MBF: F = 34.0, p <.0001; T2*: F = 73.7, p <.0001; ATT: F = 13.6, p <.001) and no average differences between slices over the total time postexercise were observed. The interaction effect between time postexercise and slice location was significant for MBF and T2* (F = 5.5, p = 0.02, F = 6.1, p = 0.02, respectively), but not for ATT (F = 2.2, p =.16). The proximal slice showed a higher MBF and a lower ATT than the distal slice during the first 2 min of recovery, and T2* showed a delayed response in the distal slice. These results imply a higher perfusion and faster microvascular response to exercise in the proximal slice, in line with previous literature. Moreover, the differences in ATT indicate that it is difficult to correctly determine perfusion based on a single PLD as is commonly performed in the muscle literature. [ABSTRACT FROM AUTHOR]

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

This review article provides an overview of the current status of velocity‐selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in‐depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo‐) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL. [ABSTRACT FROM AUTHOR]

Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine's mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine's mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions. [ABSTRACT FROM AUTHOR]

Background suppression (BGS) in arterial spin labeling (ASL) magnetic resonance imaging leads to a higher temporal signal‐to‐noise ratio (tSNR) of the perfusion images compared with ASL without BGS. The performance of the BGS, however, depends on the tissue relaxation times and on inhomogeneities of the scanner's magnetic fields, which differ between subjects and are unknown at the moment of scanning. Therefore, we developed a feedback loop (FBL) mechanism that optimizes the BGS for each subject in the scanner during acquisition. We implemented the FBL for 2D pseudo‐continuous ASL scans with an echo‐planar imaging readout. After each dynamic scan, the acquired ASL images were automatically sent to an external computer and processed with a Python processing tool. Inversion times were optimized on the fly using 80 iterations of the Nelder–Mead method, by minimizing the signal intensity in the label image while maximizing the signal intensity in the perfusion image. The performance of this method was first tested in a four‐component phantom. The regularization parameter was then tuned in six healthy subjects (three males, three females, age 24–62 years) and set as λ = 4 for all other experiments. The resulting ASL images, perfusion images, and tSNR maps obtained from the last 20 iterations of the FBL scan were compared with those obtained without BGS and with standard BGS in 12 healthy volunteers (five males, seven females, age 24–62 years) (including the six volunteers used for tuning of λ). The FBL resulted in perfusion images with a statistically significantly higher tSNR (2.20) compared with standard BGS (1.96) (p<5x10−3, two‐sided paired t‐test). Minimizing signal in the label image furthermore resulted in control images, from which approximate changes in perfusion signal can directly be appreciated. This could be relevant to ASL applications that require a high temporal resolution. Future work is needed to minimize the number of initial acquisitions during which the performance of BGS is reduced compared with standard BGS, and to extend the technique to 3D ASL. [ABSTRACT FROM AUTHOR]

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 R2(*) 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 R2(*) 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 R2(*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion. [ABSTRACT FROM AUTHOR]

Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6–13.9%; SD:7.14%; p =.003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2–76; range: 65–80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7–21.3; range: 7–30%). The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects. [ABSTRACT FROM AUTHOR]

In modern society, the widespread use of artificial light at night disrupts the suprachiasmatic nucleus (SCN), which serves as our central circadian clock. Existing models describe excitatory responses of the SCN to primarily blue light, but direct measures in humans are absent. The combination of state-of-the-art neuroimaging techniques and custom-made MRI compatible light-emitting diode devices allowed to directly measure the light response of the SCN. In contrast to the general expectation, we found that blood oxygen level-dependent (BOLD) functional MRI signals in the SCN were suppressed by light. The suppressions were observed not only in response to narrowband blue light (λmax: 470 nm) but remarkably, also in response to green (λmax: 515 nm) and orange (λmax: 590 nm), but not to violet light (λmax: 405 nm). The broadband sensitivity of the SCN implies that strategies on light exposure should be revised: enhancement of light levels during daytime is possible with wavelengths other than blue, while during nighttime, all colors are potentially disruptive. [ABSTRACT FROM AUTHOR]

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 B1 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 B1 for distinguishing different pools. Finally, the optimal B1 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 B1 = 1 μT and tmix = 10 ms and 40 ms, respectively. Fast‐exchanging components reached the highest saturation when using a B1 = 2.8 μT and tmix = 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. [ABSTRACT FROM AUTHOR]

Physical exercise affects hippocampal structure and function, but the underlying neural mechanisms and the effects of exercise intensity remain incompletely understood. Therefore, we undertook a comprehensive, multi-modal 3T and 7T MRI randomized controlled trial (Netherlands Trial Register - NL5847) in which we randomized 52 young, non-athletic volunteers to a 12-week low- or high-intensity exercise program. Using state-of-the-art methods, we investigated changes in hippocampal volume, as well as changes in vasculature, neuro-metabolites, and peripheral growth factors as potential underpinnings. Cardiorespiratory fitness improved over time (p < 0.001), but no interaction with exercise intensity was found (p = 0.48). Accordingly, we did not observe significant interactions between exercise condition and time on MRI measures (all p > 0.06). However, we found a significant decrease in right hippocampal volume (p < 0.01), an increase in left hippocampal glutathione (p < 0.01), and a decrease of left hippocampal cerebral blood volume (p = 0.01) over time, regardless of exercise condition. Additional exploratory analyses showed that changes in brain-derived neurotrophic factor (p = 0.01), insulin-like growth-factor (p = 0.03), and dorsal anterior cingulate cortex N-acetyl-aspartate levels (p = 0.01) were positively associated with cardiorespiratory fitness changes. Furthermore, a trend toward a positive association of fitness and gray-matter cerebral blood flow (p = 0.06) was found. Our results do not provide evidence for differential effects between high-intensity (aerobic) and low-intensity (toning) exercise on hippocampal structure and function in young adults. However, we show small but significant effects of exercise on hippocampal volume, neurometabolism and vasculature across exercise conditions. Moreover, our exploratory results suggest that exercise might not specifically only benefit hippocampal structure and function, but rather has a more widespread effect. These findings suggest that, in agreement with previous MRI studies demonstrating moderate to strong effects in elderly and diseased populations, but none to only mild effects in young healthy cohorts, the benefits of exercise on the studied brain measures may be age-dependent and restorative rather than stimulatory. Our study highlights the importance of a multi-modal, whole-brain approach to assess macroscopic and microscopic changes underlying exercise-induced brain changes, to better understand the role of exercise as a potential non-pharmacological intervention. [ABSTRACT FROM AUTHOR]