Arterial spin labeling perfusion fMRI with very low task frequency.

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. There are two features that make fMRI unique when compared with other imaging modalities used in behavioural neuroscience. First, it can be entirely noninvasive: each animal can serve as its own control over the natural course of its life, vital for following neuroadaptation and other developmental processes critical to understanding behaviour. Second, fMRI has the spatial and temporal resolution to observe patterns of neuronal activity across the entire brain in less than a minute. Although fMRI does not have the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, synchronised changes in neuronal activity across multiple brain areas seen with functional MRI can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviours. Thus, fMRI affords a systems approach to the study of the brain, complementing and building from other neurobiological techniques to understand how behaviour is organised across multiple brain regions. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology.

Technical aspects and utility of fMRI using BOLD and ASL

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method that provides a highly repeatable quantitative measure of cerebral blood flow (CBF). As compared to the more commonly used blood oxygenation level dependent (BOLD) contrast-based methods, ASL techniques measure a more biologically specific correlate of neural activity, with the potential for more accurate estimation of the location and magnitude of neural function. Recent advances in acquisition and analysis methods have improved the somewhat limited sensitivity of ASL to perfusion changes associated with neural activity. In addition, ASL perfusion measures are insensitive to the low-frequency fluctuations commonly observed in BOLD experiments and can make use of imaging sequences that are less sensitive than BOLD contrast to signal loss caused by magnetic susceptibility effects. ASL measures of perfusion can aid in the interpretation of the BOLD signal change and, when combined with BOLD, can measure the change in oxygen utilization accompanying changes in behavioral state. Whether used alone to probe neural activity or in combination with BOLD techniques, ASL methods are contributing to the field's understanding of healthy and disordered brain function.

BackgroundNoninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD).MethodsFifteen healthy young subjects, 14 patients with PAD, and 10 age-matched healthy old subjects underwent ASL, BOLD, and IVIM CMR perfusion imaging. Healthy young and healthy old participants were subjected to a cuff-induced ischemia experiment with pressures of 20 mmHg and 40 mmHg above systolic pressure during imaging. Perfusion-related metrics, including blood flow, T2* relaxation time, perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D*, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Friedman, Mann-Whitney, Wilcoxon signed rank, and Spearman rank correlation tests were used for statistical analysis.ResultsIn cases of significant differences determined by the Friedman test (P < 0.05), blood flow, T2*, and D values gradually decreased, while f values showed a tendency to increase in healthy subjects under cuff compression. No significant correlations were found among the ASL, BOLD, and IVIM parameters (all P > 0.05). Blood flow and T2* values showed significant positive correlations with transcutaneous oxygen pressure measurements (ρ = 0.465 and 0.522, respectively; both P ≤ 0.001), while f values showed a significant negative correlation in healthy young subjects (ρ = − 0.351; P = 0.018). T2* was independent of age in every muscle group. T2* values were significantly decreased in PAD patients compared with healthy old subjects and severe PAD patients compared with mild-to-moderate PAD patients (all P < 0.0125). Significant correlations were found between T2* and ankle–brachial index values in all muscle groups in PAD patients (ρ = 0.644–0.837; all P < 0.0125). Other imaging parameters failed to show benefits towards the diagnosis and disease severity evaluation of PAD.ConclusionsASL, BOLD, and IVIM provide complementary information regarding tissue perfusion. Compared with ASL and IVIM, BOLD may be a more reliable technique for assessing PAD in the resting state and could thus be applied together with angiography in clinical studies as a tool to comprehensively assess microvascular and macrovascular properties in PAD patients.

How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.

BackgroundThe aim of this study was to evaluate whether arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI.MethodsThirty-nine patients with acute ischemic stroke in the anterior circulation territory were recruited. All underwent ASL and DSC MRI perfusion scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI scans. ASL cerebral blood flow (CBF) and DSC time to maximum (Tmax) maps were used to calculate the perfusion defects. The ASL CBF lesion volume was compared to the DSC Tmax lesion volume by Pearson's correlation coefficient and likewise the ASL CBF and DSC Tmax lesion volumes were compared to the final infarct sizes respectively. A repeated measures analysis of variance and least significant difference post hoc test was used to compare the mean lesion volumes among ASL CBF, DSC Tmax >4–6 s and final infarct.ResultsMean patient age was 72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL lesion volume showed significant correlation with the DSC lesion volume for Tmax >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion volume of ASL (50.1 ml) was significantly larger than those for Tmax >5 s (29.2 ml, p<0.01) and Tmax >6 s (21.8 ml, p<0.001), while the mean lesion volumes for Tmax >5 or 6 s were close to mean final infarct size.ConclusionQuantitative measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL perfusion may overestimate the perfusion defects and therefore further refinement of the true penumbra threshold and improved ASL technique are necessary before applying ASL in therapeutic trials.

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level-dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed-continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised.

Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI

MRI offers techniques for non-invasively measuring a range of aspects of brain tissue function. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to assess neural activity, based on the brain's haemodynamic response, while arterial spin labelling (ASL) MRI is a non-invasive method of quantitatively mapping cerebral perfusion. Both techniques can be applied to measure cerebrovascular reactivity (CVR), an important marker of the health of the cerebrovascular system. BOLD, ASL and CVR have been applied to study a variety of disease processes and are already used in certain clinical circumstances. The brainstem is a critical component of the central nervous system and is implicated in a variety of disease processes. However, its function is difficult to study using MRI because of its small size and susceptibility to physiological noise. In this article, we review the physical and biological underpinnings of BOLD and ASL and their application to measure CVR, discuss the challenges associated with applying them to the brainstem and the opportunities for brainstem MRI in the research and clinical settings. With further optimisation, functional MRI techniques could feasibly be used to assess brainstem haemodynamics and neural activity in the clinical setting.

A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease . Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to a cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.

Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques

Vascular component analysis of hyperoxic and hypercapnic BOLD contrast

Arterial spin labeling (ASL) perfusion MRI represents a modern non-invasive approach to assessing tissue perfusion that is gaining increasing importance in clinical and research practice. Unlike traditional contrast-enhanced methods, ASL enables quantitative blood flow evaluation without the need for contrast agents, which is particularly valuable in certain clinical scenarios and for longitudinal patient monitoring. This review synthesizes current data on ASL perfusion applications, including key clinical uses and future development prospects. The topic’s relevance stems from growing interest in functional imaging techniques and the need for ASL protocol standardization to facilitate widespread clinical adoption. Purpose: To evaluate the diagnostic capabilities of ASL perfusion MRI by analyzing current applications and future development trends based on contemporary scientific evidence. Material and methods . A retrospective review of randomized clinical trials and cross-sectional studies was performed from PubMed, EMBASE, LILACS, Scopus, and eLibrary databases (2015–2025) using search terms: «arterial spin labeling,» «pulsed ASL,» «continuous ASL,» «pseudo-continuous ASL,» «diffusion-prepared ASL,» «artificial intelligence ASL,» and their Russian equivalents. Results. From 132 screened publications, 81 were selected for analysis. The review examined ASL technique variations, clinical applications, and emerging trends in the field. Conclusions. ASL perfusion is a promising non-invasive method for tissue blood flow assessment with demonstrated diagnostic utility across multiple pathologies. Future development potential lies in methodological optimization, artificial intelligence integration for data processing, and protocol standardization for routine clinical implementation.

Chapter 46 - Functional Magnetic Resonance Imaging in the Neuromodulation of Pain

A CBF-Based Event-Related Brain Activation Paradigm: Characterization of Impulse–Response Function and Comparison to BOLD