Pain response measured with arterial spin labeling

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.

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.

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.

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

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

Arterial blood stealing as a mechanism of negative BOLD response: From the steady-flow with nonlinear phase separation to a windkessel-based model

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.

Technical aspects and utility of fMRI using BOLD and ASL

Background:Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.Methods:Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated.Results:A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal.Conclusions:These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.

For the past 10 years, functional MRI (fMRI) has seen rapid progress in both clinical and basic science research. Most of the imaging techniques are based on the blood oxygenation level-dependent (BOLD) contrast which arises from the field perturbation of the paramagnetic deoxyhemoglobin due to the mismatch between the local oxygen demand and delivery. Because the changes of oxygenation level take place mostly in the veins, the dominant signal sources of the BOLD signal are intra- and extravascular proton pools of the veins. Perfusion imaging methods, developed parallel to the BOLD technique, seek to quantify the blood flow and perfusion. Recently, perfusion imaging using arterial spin tagging methods have been used to study brain function by investigating the changes of the blood flow and perfusion during brain activation, thereby generating an alternative contrast mechanism to the functional brain imaging. Since most of these methods require tagging pulse and wait time for blood to be delivered to the imaged slice, the temporal resolution may not be optimal. Dynamic intravoxel incoherent motion (IVIM) weighting schemes using apparent diffusion coefficient (ADC) contrast were suggested to image the relative changes of the in-plane blood flow during brain function. In this report, it was demonstrated that, in addition to the spatial discrepancies of the activated areas, the time course based on the ADC contrast consistently precedes that from the BOLD contrast with timing offset on the order of 1 sec. Since arterial networks would have different spatial locations and preceding temporal characters, the findings in this report are indicative that the ADC contrast is sensitive to the arterial blood flow changes.

A conceptual model for CO2-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI

We present a new method for the calculation of a blood oxygen level dependent (BOLD) signal which is meaningful for a quantitative comparison with near infrared spectroscopy (NIRS) data. Since optical tomography of the human brain still poses several difficulties, in this study we propose a way to project the BOLD signal on a two-dimensional (2D) map for comparison with NIRS data. The underlying assumption is that fMRI and NIRS are sensitive to similar aspects of the hemodynamic changes occurring during a functional task, and therefore they should have similar spatial and temporal features. We present a case study of functional activation during a finger-tapping test where we used the new method for the calculation of BOLD signal. For every optical source-detector pair we calculated a weighted BOLD signal by using a photon hitting-density weight function, and by using a simple back-projection algorithm we were able to generate BOLD 2D maps. We found that the weighted BOLD signals calculated from different source-detector pairs scale in a similar way to the corresponding oxy and deoxy-hemeoglobin concentration changes calculated from NIRS data, for most of the time range of the task. Therefore the BOLD 2D maps were quantitatively similar to the optical maps calculated at different times during the protocol.

Comment on “The physiology of developmental changes in BOLD functional imaging signals” by Harris, Reynell, and Attwell

Both transcranial direct current stimulation (tDCS) and acupuncture are promising methods for managing chronic low back pain (cLBP), however, their underlying mechanisms remain unclear. To explore the neural mechanisms of tDCS and acupuncture on cLBP, we examined how real and sham tDCS applied to the bilateral motor cortex (M1), combined with real or sham acupuncture, influenced cerebral blood flow (CBF) using pulsed continuous arterial spin labeling (pCASL) imaging. tDCS was administered over six sessions, combined with real or sham acupuncture, over one month. Following real tDCS, we observed increased CBF in the bilateral occipital cortex, precuneus, left hippocampus, and parahippocampal gyrus/posterior cingulate cortex. After sham tDCS, CBF decreased in regions including the bilateral superior parietal lobule, precuneus, bilateral precentral and postcentral gyri, and left angular gyrus. Real acupuncture led to reduced CBF in the bilateral occipital cortex and hippocampus, and left posterior cingulate gyrus, and increased CBF in the right postcentral gyrus, superior parietal lobule, and frontal areas. Sham acupuncture was associated with decreased CBF in the bilateral hippocampus and anterior cingulate gyrus. These results suggest both shared and distinct patterns of CBF changes between real and sham tDCS, as well as between real and sham acupuncture, reflecting mode-dependent effects on brain networks involved in pain processing and modulation. Our findings highlight the different neural circuits implicated in the therapeutic mechanisms of tDCS and acupuncture in the management of cLBP.

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)