Dual-echo Arterial Spin Labeling Research Articles

Semantic verbal fluency brain network: delineating a physiological basis for the functional hubs using dual-echo ASL and graph theory approach

Objective. Semantic verbal fluency (SFV) is a cognitive process that engages and modulates specific brain areas related to language comprehension and production, decision making, response inhibition, and memory retrieval. The impairment of the brain network responsible for these functions is related to various neurological conditions, and different strategies have been proposed to assess SVF-related deficits in such diseases. In the present study, the concomitant changes of brain perfusion and functional connectivity were investigated during the resting state and SVF task performance. Approach. Arterial spin labeling (ASL), a perfusion-based magnetic resonance imaging (MRI) method, was used with a pseudocontinuous labeling approach and dual-echo readout in 28 healthy right-handed Brazilian Portuguese speakers. The acquisition was performed in a resting state condition and during the performance of a SVF task. Main results. During task performance, a significant increase in cerebral blood flow (CBF) was observed in language-related regions of the frontal lobe, including Brodmann’s areas 6, 9, 45, and 47, associated with semantic processing, word retrieval, and speech motor programming. Such regions, along with the posterior cingulate, showed a crucial role in the SVF functional network, assessed by seed-to-voxel and graph analysis. Our approach successfully overcame the generalization problem regarding functional MRI (fMRI) graph analysis with cognitive, task-based paradigms. Moreover, the CBF maps enabled the functional assessment of orbital frontal and temporal regions commonly affected by magnetic susceptibility artifacts in conventional T2*-weighted fMRI approaches. Significance. Our results demonstrated the capability of ASL to evaluate perfusion alterations and functional patterns simultaneously regarding the SVF network providing a quantitative physiological basis to functional hubs in this network, which may support future clinical studies.

Compromised Resting Cerebral Metabolism After Sport-Related Concussion: A Calibrated MRI Study

Use calibrated MRI to model baseline cerebrovascular physiology parameters and investigate whether changes in resting cerebral blood flow (CBF0) following sport-related concussion (SRC) are concordant with changes in resting and dynamic cerebral physiologic markers, within two weeks of the injury. Altered CBF0 in the acute phase post-concussion may contribute to neurobehavioral deficiencies, often reported weeks after the injury. However, in addition to changes in CBF0, little is known about other physiologic mechanisms that may be disturbed within the cerebrovasculature. The aim of this study was to assess whether changes in baseline perfusion following SRC were co-localized with changes in cerebral metabolic demand. Forty-two subjects (15 SRC patients 8.0 ± 4.6 days post-injury and 27 age-matched healthy control athletes) were studied cross-sectionally. CBF0, cerebrovascular reactivity (CVR), resting oxygen extraction (OEF0) and cerebral metabolic rate of oxygen consumption (CMRO2|0) were measured using a combination of hypercapnic and hyperoxic breathing protocols, and the biophysical model developed in calibrated MRI. Blood Oxygenation Level Dependent and Arterial Spin Labelling data were acquired simultaneously using a dual-echo arterial spin labelling sequence. SRC patients showed significant decreases in CBF0 spread across the grey-matter (p < 0.05, corrected), and these differences were also confounded by the effects of baseline end-tidal CO2 (p < 0.0001). Lower perfusion was co-localized with reductions in regional CMRO2|0 (p = 0.006) post-SRC, despite finding no group-differences in OEF0 (p = 0.800). Higher CVR within voxels showing differences in CBF0 was also observed in the SRC group (p = 0.001), compared to controls. Reductions in metabolic demand despite no significant changes in OEF0 suggests that hypoperfusion post-SRC may reflect compromised metabolic function after the injury. These results provide novel insight about the possible pathophysiologic mechanisms underlying concussion that may affect the clinical recovery of athletes after sport-related head injuries.

Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = –0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Compromised resting cerebral metabolism after sport-related concussion: A calibrated MRI study

Altered resting cerebral blood flow (CBF0) in the acute phase post-concussion may contribute to neurobehavioral deficiencies, often reported weeks after the injury. However, in addition to changes in CBF0, little is known about other physiological mechanisms that may be disturbed within the cerebrovasculature. The aim of this study was to assess whether changes in baseline perfusion following sport-related concussion (SRC) were co-localized with changes in cerebral metabolic demand. Forty-two subjects (15 SRC patients 8.0 ± 4.6days post-injury and 27 age-matched healthy control athletes) were studied cross-sectionally. CBF0, cerebrovascular reactivity (CVR), resting oxygen extraction (OEF0) and cerebral metabolic rate of oxygen consumption (CMRO2|0) were measured using a combination of hypercapnic and hyperoxic breathing protocols, and the biophysical model developed in calibrated MRI. Blood oxygenation level dependent and perfusion data were acquired simultaneously using a dual-echo arterial spin labelling sequence. SRC patients showed significant decreases in CBF0 spread across the grey-matter (P < 0.05, corrected), and these differences were also confounded by the effects of baseline end-tidal CO2 (P < 0.0001). Lower perfusion was co-localized with reductions in regional CMRO2|0 (P = 0.006) post-SRC, despite finding no group-differences in OEF0 (P = 0.800). Higher CVR within voxels showing differences in CBF was also observed in the SRC group (P = 0.001), compared to controls. Reductions in metabolic demand despite no significant changes in OEF0 suggests that hypoperfusion post-SRC may reflect compromised metabolic function after the injury. These results provide novel insight about the possible pathophysiological mechanisms underlying concussion that may affect the clinical recovery of athletes after sport-related head injuries.

Dual-Echo Arterial Spin Labeling for Brain Perfusion Quantification and Functional Analysis

Arterial Spin Labeling (ASL) is a noninvasive MRI-based method to measure cerebral blood flow (CBF). Recently, the study of ASL as a functional tool has emerged once CBF fluctuation comes from capillaries in brain tissue, giving a more spatially specific response when compared to the standard functional MRI method, based on the blood oxygenation level-dependent (BOLD) contrast. Although the BOLD effect could be desirable to study brain function, if one aims to quantify CBF, such effect is considered contamination that can be more attenuated if short TE value is used in the image acquisition. An approach that provides both CBF and function information in a simultaneous acquisition is the use of a dual-echo ASL (DE-ASL) readout. Our purpose was to evaluate the information provided by DE-ASL regarding CBF quantification and functional connectivity with a motor task. Pseudocontinuous ASL of twenty healthy subjects (age: 32.4 ± 10.2 years, 13 male) was acquired at a 3T scanner. We analyzed the influence of TE on CBF values and brain connectivity provided by CBF and concurrent BOLD (cc-BOLD) time series. Brain networks were obtained by the general linear model and independent component analysis. Connectivity matrices were generated using a bivariate correlation (Fisher Z values). No effect of the sequence readout, but significant effect of the TE value, was observed on gray matter CBF values. Motor networks with reduced extension and more connections with important regions for brain integration were observed for CBF data acquired with short TE, proving its higher spatial specificity. Therefore, it was possible to use a dual-echo readout provided by a standard commercial ASL pulse sequence to obtain reliable quantitative CBF values and functional information simultaneously.

Dual-echo ASL based assessment of motor networks: a feasibility study

Objective. Dual-echo arterial spin labeling (DE-ASL) technique has been recently proposed for the simultaneous acquisition of ASL and blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) data. The assessment of this technique in detecting functional connectivity at rest or during motor and motor imagery tasks is still unexplored both per-se and in comparison with conventional methods. The purpose is to quantify the sensitivity of the DE-ASL sequence with respect to the conventional fMRI sequence (cvBOLD) in detecting brain activations, and to assess and compare the relevance of node features in decoding the network structure. Approach. Thirteen volunteers were scanned acquiring a pseudo-continuous DE-ASL sequence from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. The approach consists of two steps: (i) model-based analyses for assessing brain activations at individual and group levels, followed by statistical analysis for comparing the activation elicited by the three sequences under two conditions (motor and motor imagery), respectively; (ii) brain connectivity graph-theoretical analysis for assessing and comparing the network models properties. Main results. Our results suggest that cvBOLD and ccBOLD have comparable sensitivity in detecting the regions involved in the active task, whereas ASL offers a higher degree of co-localization with smaller activation volumes. The connectivity results and the comparative analysis of node features across sequences revealed that there are no strong changes between rest and tasks and that the differences between the sequences are limited to few connections. Significance. Considering the comparable sensitivity of the ccBOLD and cvBOLD sequences in detecting activated brain regions, the results demonstrate that DE-ASL can be successfully applied in functional studies allowing to obtain both ASL and BOLD information within a single sequence. Further, DE-ASL is a powerful technique for research and clinical applications allowing to perform quantitative comparisons as well as to characterize functional connectivity.

Effects of background suppression on the sensitivity of dual-echo arterial spin labeling MRI for BOLD and CBF signal changes

Dual-echo arterial spin labeling (DE-ASL) enables the simultaneous acquisition of BOLD and CBF fMRI data and is often used for calibrated BOLD and cerebrovascular CO2 reactivity measurements. DE-ASL, like all ASL techniques, suffers from a low intrinsic CBF SNR, which can be improved by suppressing the background signal via the inclusion of additional inversion pulses. However, until now this approach has been considered to be undesirable for DE-ASL, because the BOLD signal is extracted from the background signal and attenuating the background signal could decrease the sensitivity of DE-ASL scans for BOLD changes. In this study, the effect of background suppression on the sensitivity of DE-ASL MRI for BOLD and CBF signal changes with a visual stimulation paradigm was studied. Results showed that with an average background suppression level of 70% the BOLD sensitivity of DE-ASL MRI decreases slightly (15%), while the CBF sensitivity of the scans increased by almost a factor-of-two (81%). These findings support the conclusion that the gains in CBF sensitivity of DE-ASL MRI due to background suppression outweigh the slight decrease in sensitivity of these scans for BOLD changes, and thus that background suppression is highly recommended for DE-ASL.

A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex.

Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task performance.

Neural mechanisms of age-related slowing: the ΔCBF/ΔCMRO2 ratio mediates age-differences in BOLD signal and human performance.

The precise mechanisms that give rise to the blood-oxygen-level-dependent (BOLD) activation differences that accompany age-related cognitive slowing remain fundamentally unknown. We sought to isolate the origin of age-related BOLD changes by comparing blood-flow and oxygen-metabolic constituents of the BOLD response using dual-echo arterial spin labeling during visual stimulation and CO2 ingestion. We hypothesized, and our results confirmed, that age-related changes in the ratio of fractional cerebral blood flow to fractional cerebral metabolic rate of oxygen consumption (ΔCBF/ΔCMRO2) lead to the BOLD changes that are observed in older adults. ΔCBF/ΔCMRO2 was also significantly related to performance, suggesting that age-related cognitive slowing results from neural cell assemblies that operate less efficiently, requiring greater oxygen metabolism that is not matched by blood-flow changes relative to younger adults. Age-related changes in ΔCBF/ΔCMRO2 are sufficient to explain variations in BOLD responding and performance cited throughout the literature, assuming no bias based on physiological baseline CMRO2.

Thirty minute transcutaneous electric acupoint stimulation modulates resting state brain activities: A perfusion and BOLD fMRI study

Increasing neuroimaging studies have focused on the sustained after effects of acupuncture, especially for the changes of brain activities in rest. However, short-period stimuli have mostly been chosen in these works. The present study aimed to investigate how the resting state brain activities in healthy subjects were modulated by relatively long-period (30min) acupuncture, a widely used modality in clinical practice. Transcutaneous electric acupoint stimulation (TEAS) or intermittent minimal TEAS (MTEAS) were given for 30min to 40 subjects. Functional MRI (fMRI) data were collected including the pre-stimulation resting state and the post-stimulation resting state, using dual-echo arterial spin labeling (ASL) techniques, representing both cerebral blood flow (CBF) signals and blood oxygen-dependent level (BOLD) signals simultaneously. Following 30min TEAS, but not MTEAS, the mean global CBF decreased, and a significant decrease of regional CBF was observed in SI, insula, STG, MOG and IFG. Functional connectivity analysis showed more secure and spatially extended connectivity of both the DMN and SMN after 30min TEAS. Our results implied that modulation of the regional brain activities and network connectivity induced by thirty minute TEAS may associate with the acupuncture-related therapeutic effects. Furthermore, the resting state regional CBF quantified by ASL perfusion fMRI may serve as a potential biomarker in future acupuncture studies.

SNR and functional sensitivity of BOLD and perfusion-based fMRI using arterial spin labeling with spiral SENSE at 3 T

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies using parallel imaging to reduce the readout window have reported a loss in temporal signal-to-noise ratio (SNR) that is less than would be expected given a purely thermal noise model. In this study, the impact of parallel imaging on the noise components and functional sensitivity of both BOLD and perfusion-based fMRI data was investigated. Dual-echo arterial spin labeling data were acquired on five subjects using sensitivity encoding (SENSE), at reduction factors (R) of 1, 2 and 3. Direct recording of cardiac and respiratory activity during data acquisition enabled the retrospective removal of physiological noise. The temporal SNR of the perfusion time series closely followed the thermal noise prediction of a radicalR loss in SNR as the readout window was shortened, with temporal SNR values (relative to the R=1 data) of 0.72 and 0.56 for the R=2 and R=3 data, respectively, after accounting for physiological noise. However, the BOLD temporal SNR decreased more slowly than predicted even after accounting for physiological noise, with relative temporal SNR values of 0.80 and 0.63 for the R=2 and R=3 data, respectively. Spectral analysis revealed that the BOLD trends were dominated by low-frequency fluctuations, which were not dominant in the perfusion data due to signal processing differences. The functional sensitivity, assessed using mean F values over activated regions of interest (ROIs), followed the temporal SNR trends for the BOLD data. However, results for the perfusion data were more dependent on the threshold used for ROI selection, most likely due to the inherently low SNR of functional perfusion data.

Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated BOLD fMRI study

Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO 2). In this study, we implemented a quantitative R 2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO 2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+ 46.6%, ± 11.3, mean and standard error), visual stimulation increased both CBF (+ 47.9%, ± 2.9) and CMRO 2 (+ 20.7%, ± 1.4), and caffeine decreased CBF (− 34.5%, ± 2.6) with a non-significant change in CMRO 2 (+ 5.2%, ± 6.4). The coupling between CBF and CMRO 2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R 2∗ is a promising approach for evaluating CBF and CMRO 2 changes in response to pharmacological interventions.