Estimated gray matter volume rapidly changes after a short motor task.

Skill learning induces changes in estimates of gray matter volume (GMV) in the human brain, commonly detectable with magnetic resonance imaging (MRI). Rapid changes in GMV estimates while executing tasks may however confound between- and within-subject differences. Fluctuations in arterial blood flow are proposed to underlie this apparent task-related tissue plasticity. To test this hypothesis, we acquired multiple repetitions of structural T1-weighted and functional blood-oxygen level-dependent (BOLD) MRI measurements from 51 subjects performing a finger-tapping task (FTT; á 2 min) repeatedly for 30-60 min. Estimated GMV was decreased in motor regions during FTT compared with rest. Motor-related BOLD signal changes did not overlap nor correlate with GMV changes. Nearly simultaneous BOLD signals cannot fully explain task-induced changes in T1-weighted images. These sensitive and behavior-related GMV changes pose serious questions to reproducibility across studies, and morphological investigations during skill learning can also open new avenues on how to study rapid brain plasticity.

CS-MRI Reconstruction Using an Improved GAN with Dilated Residual Networks and Channel Attention Mechanism.

Compressed sensing (CS) MRI has shown great potential in enhancing time efficiency. Deep learning techniques, specifically generative adversarial networks (GANs), have emerged as potent tools for speedy CS-MRI reconstruction. Yet, as the complexity of deep learning reconstruction models increases, this can lead to prolonged reconstruction time and challenges in achieving convergence. In this study, we present a novel GAN-based model that delivers superior performance without the model complexity escalating. Our generator module, built on the U-net architecture, incorporates dilated residual (DR) networks, thus expanding the network's receptive field without increasing parameters or computational load. At every step of the downsampling path, this revamped generator module includes a DR network, with the dilation rates adjusted according to the depth of the network layer. Moreover, we have introduced a channel attention mechanism (CAM) to distinguish between channels and reduce background noise, thereby focusing on key information. This mechanism adeptly combines global maximum and average pooling approaches to refine channel attention. We conducted comprehensive experiments with the designed model using public domain MRI datasets of the human brain. Ablation studies affirmed the efficacy of the modified modules within the network. Incorporating DR networks and CAM elevated the peak signal-to-noise ratios (PSNR) of the reconstructed images by about 1.2 and 0.8 dB, respectively, on average, even at 10× CS acceleration. Compared to other relevant models, our proposed model exhibits exceptional performance, achieving not only excellent stability but also outperforming most of the compared networks in terms of PSNR and SSIM. When compared with U-net, DR-CAM-GAN's average gains in SSIM and PSNR were 14% and 15%, respectively. Its MSE was reduced by a factor that ranged from two to seven. The model presents a promising pathway for enhancing the efficiency and quality of CS-MRI reconstruction.

Functional connectivity in reward-related networks is associated with individual differences in gambling strategies in male Lister hooded rats.

Individuals with gambling disorder display deficits in decision-making in the Iowa Gambling Task. The rat Gambling Task (rGT) is a rodent analogue that can be used to investigate the neurobiological mechanisms underlying gambling behaviour. The aim of this explorative study was to examine individual strategies in the rGT and investigate possible behavioural and neural correlates associated with gambling strategies. Thirty-two adult male Lister hooded rats underwent behavioural testing in the multivariate concentric square field™ (MCSF) and the novel cage tests, were trained on and performed the rGT and subsequently underwent resting-state functional magnetic resonance imaging (R-fMRI). In the rGT, stable gambling strategies were found with subgroups of rats that preferred the suboptimal safest choice as well as the disadvantageous choice, that is, the riskiest gambling strategy. R-fMRI results revealed associations between gambling strategies and brain regions central for reward networks. Moreover, rats with risky gambling strategies differed from those with strategic and intermediate strategies in brain functional connectivity. No differences in behavioural profiles, as assessed with the MCSF and novel cage tests, were observed between the gambling strategy groups. In conclusion, stable individual differences in gambling strategies were found. Intrinsic functional connectivity using R-fMRI provides novel evidence to support the notion that individual differences in gambling strategies are associated with functional connectivity in brain regions important for reward networks.

Viewing Pictures Triggers Rapid Morphological Enlargement in the Human Visual Cortex.

Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals' current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.

Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia: a case report.

BACKGROUND: Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies. CASE PRESENTATION: Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. CONCLUSIONS: We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.

Behavioral correlates of changes in hippocampal gray matter structure during acquisition of foreign vocabulary.

Experience can affect human gray matter volume. The behavioral correlates of individual differences in such brain changes are not well understood. In a group of Swedish individuals studying Italian as a foreign language, we investigated associations among time spent studying, acquired vocabulary, baseline performance on memory tasks, and gray matter changes. As a way of studying episodic memory training, the language learning focused on acquiring foreign vocabulary and lasted for 10weeks. T1-weighted structural magnetic resonance imaging and cognitive testing were performed before and after the studies. Learning behavior was monitored via participants' use of a smartphone application dedicated to the study of vocabulary. A whole-brain analysis showed larger changes in gray matter structure of the right hippocampus in the experimental group (N=33) compared to an active control group (N=23). A first path analyses revealed that time spent studying rather than acquired knowledge significantly predicted change in gray matter structure. However, this association was not significant when adding performance on baseline memory measures into the model, instead only the participants' performance on a short-term memory task with highly similar distractors predicted the change. This measure may tap similar individual difference factors as those involved in gray matter plasticity of the hippocampus.

Changes in perceptual speed and white matter microstructure in the corticospinal tract are associated in very old age.

The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103 years) assessed twice with a retest interval of 2.3 years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition.

CHANGES IN FUNCTIONAL CONNECTIVITY FOLLOWING INTENSIVE ATTENTION TRAINING IN PATIENTS WITH TRAUMATIC BRAIN INJURY. A PILOT STUDY.

Objective: To explore functional connectivity after intensive attention training in the chronic phase after traumatic brain injury as clinical evidence indicates that intensive attention training improves attention dysfunction in persons with traumatic brain injury. Design and subjects: A case series study. Two young adults, 13- and 18-months post traumatic brain injury, with traumatic brain injury induced attention deficits were assigned to 20 h of intensive attention training and neuroimaging. Methods: Functional magnetic resonance imaging during a psychomotor vigilance test was conducted pre- and post-intervention. Results: The neuroimaging indicated both increased and decreased connectivity density in frontal, posterior and subcortical brain regions, for some regions with separate change patterns for left and right hemisphere respectively, and an overall reduction in variability in functional connectivity. Conclusion: The changed and decreased variability of functional connectivity in various brain regions, captured by fMRI during a psychomotor vigilance test after direct attention training in a small sample of persons with traumatic brain injury, suggests further studies of functional connectivity changes in neural networks.

Age-dependent effects of oxytocin in brain regions enriched with oxytocin receptors.

Although intranasal oxytocin administration to tap into central functions is the most commonly used non-invasive means for exploring oxytocin's role in human cognition and behavior, the way by which intranasal oxytocin acts on the brain is not yet fully understood. Recent research suggests that brain regions densely populated with oxytocin receptors may play a central role in intranasal oxytocin's action mechanisms in the brain. In particular, intranasal oxytocin may act directly on (subcortical) regions rich in oxytocin receptors via binding to these receptors while only indirectly affecting other (cortical) regions via their neural connections to oxytocin receptor-enriched regions. Aligned with this notion, the current study adopted a novel approach to test 1) whether the connections between oxytocin receptor-enriched regions (i.e., the thalamus, pallidum, caudate nucleus, putamen, and olfactory bulbs) and other regions in the brain were responsive to intranasal oxytocin administration, and 2) whether oxytocin-induced effects varied as a function of age. Forty-six young (24.96 ± 3.06 years) and 44 older (69.89 ± 2.99 years) participants were randomized, in a double-blind procedure, to self-administer either intranasal oxytocin or placebo before resting-state fMRI. Results supported age-dependency in the effects of intranasal oxytocin administration on connectivity between oxytocin receptor-enriched regions and other regions in the brain. Specifically, compared to placebo, oxytocin decreased both connectivity density and connectivity strength of the thalamus for young participants while it increased connectivity density and connectivity strength of the caudate for older participants. These findings inform the mechanisms underlying the effects of exogenous oxytocin on brain function and highlight the importance of age in these processes.

Altered empathy processing in frontotemporal dementia A task-based fMRI study.

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the controls activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The controls rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informants ratings of the patients empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient's self-ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patients capacity to experience affective empathy.

Cortical responses to amphetamine exposure studied by pCASL MRI and pharmacokinetic/pharmacodynamic dose modeling.

INTRODUCTION: Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for pharmaceutical magnetic resonance imaging (phMRI) studies to investigate how drugs change the cerebral perfusion status and further, neuronal activity. MATERIALS AND METHOD: Twelve healthy normal male volunteers participated in the study which was based on a double blinded design. Six subjects were randomly selected to receive a single oral dose of 20mg d-amphetamine and six were given placebo. Perfusion measurements by pseudo-continuous ASL (pCASL) technique were repeatedly performed at 10 different time points with a 3T clinical MRI scanner during a 10 hour period after dose together with physiologic data and blood sample collections. The dynamic changes in cerebral perfusion in response to the plasma concentration variations of d-amphetamine were analyzed at voxel-level and for regions of interest. RESULTS: Compared to the placebo group a 20% reduction in cerebral blood flow (CBF) was observed in gray matter for the subjects that received d-amphetamine. The most significant reduction of regional CBF (rCBF) was detected in the basal ganglia, frontal region and insular cortex using voxel based analysis. A relation between d-amphetamine exposure and CBF response was found using PK/PD modeling, which predicted on average a 15% decrease of the CBF in gray matter at a plasma concentration of 30 ng/ml. CONCLUSION: In this study we have demonstrated that repeated perfusion measurements by pCASL technique was sufficiently robust to differentiate the neurological response between the groups that received d-amphetamine and placebo. Quantitative and repetitive CBF measurements can be used for PK/PD modeling of CNS drug responses in humans.

The dimensionality of between-person differences in white matter microstructure in old age.

Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60-87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general.

Pseudo-continuous arterial spin labeling at 7 T for human brain: estimation and correction for off-resonance effects using a Prescan.

Pseudo-continuous arterial spin labeling (ASL) can provide best signal-to-noise ratio efficiency with a sufficiently long tag at high fields such as 7 T, but it is very sensitive to off-resonance fields at the tagging location. Here, a robust Prescan procedure is demonstrated to estimate the pseudo-continuous ASL radiofrequency phase and gradients parameters required to compensate the off-resonance effects at each vessel location. The Prescan is completed in 1-2 min and is based on acquisition of label/control pair-wise ASL data as a function of the radiofrequency phase increment applied to the pseudo-continuous ASL train. It is shown that this approach can be used to acquire high quality whole-brain pseudo-continuous ASL perfusion data of the human brain at 7 T.

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast.

Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region's myeloarchitecture and forms the dominant source of the observed MRI contrast.

Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance.

Myalgic encephalomyelitis (ME) previously also known as chronic fatigue syndrome is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here, we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation targeting nerve endings in the nasal cavity, likely from the trigeminal nerve, possibly activating additional centers in the brainstem of ME patients and correlating with a ∼30% reduction in overall symptom scores after 8 weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover signs of chronic immune activation in ME, as well as immunological correlates of improvement that center around gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remain to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We believe that these results are suggestive of ME as a condition explained by a maladaptive disease tolerance response following infection.

Accelerating Dynamic MRI Reconstruction Using Adaptive Sequentially Truncated Higher-Order Singular Value Decomposition.

BACKGROUND: Dynamic magnetic resonance imaging (dMRI) plays an important role in cardiac perfusion and functional clinical exams. However, further applications are limited by the speed of data acquisition. OBJECTIVE: A low-rank plus sparse decomposition approach is often introduced for reconstructing dynamic magnetic resonance imaging (dMRI) from highly under-sampling K-space data. In this paper, the reconstruction problem of DMR is transformed into a low-rank tensor plus sparse tensor recovery problem. METHODS: A sequentially truncated higher-order singular value decomposition method is proposed to quickly approximate the low-rank tensor space structure and learn sparse components by adding a tensor kernel norm to the low-rank tensor and a l1 norm to the sparse tensor to constrain the two parts at the same time. The optimization problem is solved by using the iterative soft-thresholding algorithm; therefore, under the premise of ensuring the accuracy of the data, the amount of computation can be effectively reduced. RESULTS: Compared with the state-of-the-art methods, the experimental results show that the proposed method can achieve better performance in terms of reconstruction speed and reconstruction quality on 3D and 4D dMRI datasets. CONCLUSION: The multidimensional MRI time series is represented by the tensor tool and decomposed into low rank tensor terms and sparse tensor terms. The low rank spatial structure is captured by the adaptive ST-HOSVD for fast approximation and the sparse component is constrained efficiently with a sparsity transform and l1 norm. The optimization problem is solved by an iterative soft-thresholding algorithm. Through extensive 3D and 4D dMRI experiments, it is demonstrated that our method can achieve superior reconstruction performance and efficiency compared with the other three state-of-theart methods reported in the literature.

Quantifying the impact of Pyramid Squeeze Attention mechanism and filtering approaches on Alzheimer's disease classification.

Brain medical imaging and deep learning are important foundations for diagnosing and predicting Alzheimer's disease. In this study, we explored the impact of different image filtering approaches and Pyramid Squeeze Attention (PSA) mechanism on the image classification of Alzheimer's disease. First, during the image preprocessing, we register MRI images and remove skulls, then apply median filtering, Gaussian blur filtering, and anisotropic diffusion filtering to obtain different experimental images. After that, we add the Squeeze and Excitation (SE) mechanism and Pyramid Squeeze Attention (PSA) mechanism to the Fully Convolutional Network (FCN) model respectively, to obtain each MRI image's corresponding feature information of disease probability map. Besides, we also construct Multi-Layer Perceptron (MLP) model's framework, combining feature information of disease probability map with age, gender, and Mini-Mental State Examination (MMSE) of each sample, to get the final classification performance of model. Among them, the accuracy of the MLP-C model combining anisotropic diffusion filtering with the Pyramid Squeeze Attention mechanism can reach 98.85%. The corresponding quantitative experimental results show that different image filtering approaches and attention mechanisms provide effective assistance for the diagnosis and classification of Alzheimer's disease.

The contribution of chemical exchange to MRI frequency shifts in brain tissue.

Recent high-field MRI studies based on resonance frequency contrast have revealed brain structure with unprecedented detail. Although subtle magnetic susceptibility variations caused by iron and myelin seem to be important to this contrast, recent research on protein solutions suggests that chemical exchange between water and macromolecular protons may contribute substantially to the observed gray-white matter frequency contrast. To investigate this, we performed spectroscopic MRI experiments at 14 T on samples of fixed human visual cortex and fresh pig brain. To allow direct observation of any exchange-induced frequency shifts, these samples were soaked in reference chemicals (TSP and dioxane) that are assumed not to be involved in exchange. For both fresh and fixed tissues and with both reference chemicals, substantial negative exchange-induced gray-white matter frequency contrast (-6.3 to -13.5 ppb) was found, whereas intracortical contrast was negligible. The sign of the gray-white matter exchange-induced frequency difference was opposite to the overall gray-white matter frequency difference observed in vivo. This suggests that exchange contributes to, but is not sufficient to explain, the frequency contrast in vivo and tissue susceptibility differences may have a greater contribution than previously thought. The exchange-dependent contribution may report on tissue chemical composition and pH.

Transmit B1-field correction at 7 T using actively tuned coupled inner elements.

When volume coils are used for (1)H imaging of the human head at 7 T, wavelength effects in tissue cause a variation in intensity, that is typically brighter at the center of the head and darker in the periphery. Much of this image nonuniformity can be attributed to variation in the effective transmit B(1) field, which falls by ∼ 50% to the left and right of center at mid-elevation in the brain. Because most of this B(1) loss occurs in the periphery of the brain, we have explored use of actively controlled, off-resonant loop elements to locally enhance the transmit B(1) field in these regions. When tuned to frequencies above the NMR frequency, these elements provide strong local enhancement of the B(1) field of the transmit coil. Because they are tuned off-resonance, some volume coil detuning results, but resistive loading of the coil mode remains dominated by the sample. By digitally controlling their frequency offsets, the field enhancement of each inner element can be placed under active control. Using an array of eight digitally controlled elements placed around a custom-built head phantom, we demonstrate the feasibility of improving the B(1) homogeneity of a transmit/receive volume coil without the need for multiple radio frequency transmit channels.

The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques.

The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel-based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS).