Arterial Spin Labeling Perfusion MRI Research Articles

IC‐P‐056: Cerebral blood flow changes in early Alzheimer's disease: A high‐field arterial spin labeling perfusion MRI study

IC‐P‐056: Cerebral blood flow changes in early Alzheimer's disease: A high‐field arterial spin labeling perfusion MRI study

IC‐P‐118: Cerebral blood flow measured with arterial spin–labeled perfusion MRI at 3T and structural brain changes in Alzheimer's disease

IC‐P‐118: Cerebral blood flow measured with arterial spin–labeled perfusion MRI at 3T and structural brain changes in Alzheimer's disease

P2‐252: Cerebral blood flow changes in early Alzheimer's disease: A high‐field arterial spin labeling perfusion MRI study

P2‐252: Cerebral blood flow changes in early Alzheimer's disease: A high‐field arterial spin labeling perfusion MRI study

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia

While our previous work suggests that the midazolam-induced memory impairment results from the inhibition of new association formation, little is known about the neural correlates underlying these effects beyond the effects of GABA agonists on the brain. We used arterial spin-labeling perfusion MRI to measure cerebral blood flow changes associated with the effects of midazolam on ability to learn arbitrary word-pairs. Using a double-blind, within-subject cross-over design, subjects studied word-pairs for a later cued-recall test while they were scanned. Lists of different word-pairs were studied both before and after an injection of either saline or midazolam. As expected, recall was severely impaired under midazolam. The contrast of MRI signal before and after midazolam administration revealed a decrease in CBF in the left dorsolateral prefrontal cortex (DLPFC), left cingulate gyrus and left posterior cingulate gyrus/precuneus. These effects were observed even after controlling for any effect of injection. A strong correlation between the midazolam-induced changes in neural activity and memory performance was found in the left DLPFC. These findings provide converging evidence that this region plays a critical role in the formation of new associations and that low functioning of this region is associated with anterograde amnesia.

Stroke: Highlights of Selected Articles

<i>Stroke:</i> Highlights of Selected Articles

Assessment of Cholinergic and Cognitive Function in Healthy Young Adults Using Pharmacologic ASL Perfusion MRI (S29.003)

Objective: To examine the cholinergic system in vivo using pharmacologic arterial spin-labeling (ASL) perfusion MRI. Background In vivo imaging of cholinergic function has the potential of advancing our understanding of the important role it plays in cognition. Pharmacologic MRI, by examining changes in cerebral blood flow (CBF) following drug administration, can elucidate physiological effects with high anatomic resolution in vivo and thereby link the cognitive effects of cholinergic modulation to specific anatomical structures. Design/Methods: Healthy young adults participated in a randomized, placebo-controlled crossover study (n=15). Each underwent four pharmacologic conditions (placebo, mecamylamine, scopolamine, mecamylamine+scopolamine) on four separate days. ASL scans were obtained at the time of peak drug concentration, and cognitive performance was assessed with a neuropsychological battery. SPM was used to identify regions of significantly altered CBF in clusters of at least 1800 voxels. Cognitive performance was analyzed with repeated measures ANOVA. Results: With scopolamine, CBF was decreased bilaterally in thalamus, frontal cortex, and supplementary motor area and increased in occipital cortex, postcentral gyrus, insula, hippocampus, and superior temporal pole (corrected p-value Conclusions: These results confirm previous findings of decreased frontal and thalamic perfusion and cognitive deficits with scopolamine and reveal other areas implicated in cognition with cholinergically modulated blood flow, suggesting that ASL may be more sensitive to the perfusion changes under study. The cognitive impairments with cholinergic antagonism, including impaired attention and encoding, are consistent with disruption of the attention network (eg. frontal cortex, supplementary motor area, thalamus, basal ganglia). Likewise memory deficits could result from disruptions of known memory structures (eg. hippocampus) or decreased activity of inhibitory thalamic projections to cortical structures. Supported by: This project was funded by the American Federation for Aging Research Medical Student Training in Aging Research (MSTAR) Program, NIH/NIA grants T35AG038027, T32AG023480, K23AG031320, the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, and the American Academy of Neurology Medical Student Summer Research Scholarship. Disclosure: Dr. Huang has nothing to disclose. Dr. Dai has nothing to disclose. Dr. Alsop has nothing to disclose. Dr. Waterston has nothing to disclose. Dr. Inouye has nothing to disclose. Dr. Fong has nothing to disclose.

Whole-Brain Arterial Spin Labeling Perfusion MRI in Patients With Acute Stroke

Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging. Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion-perfusion mismatches. One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0-17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10-116] versus 114 [41-225] mL; P=0.01). ASL can depict large perfusion deficits and perfusion-diffusion mismatches in correspondence with DSC. Our findings show that a fast 2&frac12;-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents.

The Value of Arterial Spin-Labeled Perfusion Imaging in Acute Ischemic Stroke

The purpose of this study was to evaluate the potential clinical value of arterial spin-labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) through comparison with dynamic susceptibility contrast (DSC) enhanced perfusion MRI. Pseudocontinuous ASL with 3-dimensional background-suppressed gradient and spin echo readout was applied with DSC perfusion MRI on 26 patients with AIS. ASL cerebral blood flow and multiparametric DSC perfusion maps were rated for image quality and lesion severity/conspicuity. Mean ASL cerebral blood flow and DSC perfusion values were obtained in main vascular territories. Kendall coefficient of concordance was calculated to evaluate the reliability of ratings. Spearman correlation coefficients were calculated to compare ratings and quantitative perfusion values between ASL and DSC perfusion maps. ASL cerebral blood flow and DSC perfusion maps provided largely consistent results in delineating hypoperfused brain regions in AIS. Hyperemic lesions, which also appeared frequently in the AIS cases studied, were more conspicuous on ASL cerebral blood flow than on DSC cerebral blood flow, mean transit time and time to the maximum of the tissue residual function maps. As a rapid, noninvasive, and quantitative technique, ASL has clinical use in detecting blood flow abnormalities in patients with AIS.

Abstract 1905: Arterial Spin-Labeled MRI of Leptomeningeal Collateral Perfusion in Acute Ischemic Stroke

Background: Leptomeningeal collaterals and associated cortical perfusion downstream from a proximal arterial occlusion or stenosis are potent predictors of outcome in acute stroke. Arterial spin-labeled (ASL) MRI may depict delayed arterial transit effects (DATE) of these collaterals and cerebral blood flow (CBF), utilizing noninvasive techniques without the use of contrast. We conducted a prospective validation study of ASL DATE and CBF as biomarkers of leptomeningeal collateral perfusion compared to digital subtraction angiography (DSA) and dynamic susceptibility contrast (DSC) perfusion MRI in acute ischemic stroke. Methods: Consecutive anterior circulation acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL, DSA and DSC perfusion MRI within 12 hours of symptom onset. ASL DATE extent was scored using a 3-point scale and angiographic collaterals on the DSA graded using the ASITN/SIR collateral score. ASL CBF and DSC CBF maps were co-registered to derive comparative ROI statistics on perfusion in the symptomatic territory. ASL CBF lesions &lt; 15 mL/100 g/min were used to measure DSC CBF values within coregistered ROIs. Results: Among 39 patients meeting entry criteria, mean age was 66±19 years and 51% were male. All 39 patients were imaged with ASL and DSA, with DSC perfusion MRI in a subset of 27. Sites of vascular occlusion or stenosis were: terminal ICA - 10, M1 MCA - 20, M2 MCA - 5 and more distal MCA - 4. ASL DATE scores ranged from 0-2, with a median of 1. DSA collateral grade ranged from 0-4, with a median of 2. Overall, there was strong correlation (r=0.702, p&lt;0.001) between the ASL and DSA measures of leptomeningeal collateral supply. In the downstream territory from these leptomeningeal collaterals, ASL CBF and DSC CBF maps both revealed hypoperfusion in regions that closely matched. Only limited correlation, however, was noted between exact ASL CBF and DSC CBF values within the co-registered ROIs. Conclusions: ASL MRI provides an accurate, noninvasive measure of leptomeningeal collateral perfusion in acute ischemic stroke due to anterior circulation stenosis or occlusion. ASL CBF measures of collateral perfusion likely are arterially weighted, like DSA collateral grades, and unlike conventional DSC perfusion MRI CBF values.

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease

We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. Fifteen patients with AD (mean age 72 ± 6 years, Mini-Mental State Examination score [MMSE] 20 ± 6) and 19 age-matched controls (mean age 68 ± 6 years, MMSE 29 ± 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies.

Imaging of Experimental Stroke Models

The ischemic penumbra is the target of acute stroke therapy. It can be approximated on diffusion/perfusion MRI as the ischemic region with abnormal perfusion and normal diffusion imaging. Using arterial spin labeling perfusion MRI and diffusion MRI, our group has studied the evolution of the diffusion/perfusion mismatch in rat stroke models. Additionally, we have evaluated the effects of high-flow oxygen on the natural history of penumbral evolution, demonstrating that high-flow oxygen "freezes" the evolution of the mismatch and allows for later beneficial use of intravenous tissue plasminogen activator (tPA). Two neuroprotective drugs, Granulocyte colony stimulating factor and a PSD95 inhibitor both impeded the evolution of the mismatch into infarcted tissue in vivo and by histological analysis. Employing a novel technique of clot imaging, our group was able to demonstrate that the combination of tPA plus Annexin-2 was superior to tPA alone in dissolving an embolus and also in reducing the extent of hypoperfused brain tissue of perfusion imaging. The use of these advanced MRI techniques in animal experiments will help to advance clinical imaging of the ischemic penumbra and hopefully contribute to the extension of the therapeutic time window in stroke patients.

Reduced resolution transit delay prescan for quantitative continuous arterial spin labeling perfusion imaging

Arterial spin labeling perfusion MRI can suffer from artifacts and quantification errors when the time delay between labeling and arrival of labeled blood in the tissue is uncertain. This transit delay is particularly uncertain in broad clinical populations, where reduced or collateral flow may occur. Measurement of transit delay by acquisition of the arterial spin labeling signal at many different time delays typically extends the imaging time and degrades the sensitivity of the resulting perfusion images. Acquisition of transit delay maps at the same spatial resolution as perfusion images may not be necessary, however, because transit delay maps tend to contain little high spatial resolution information. Here, we propose the use of a reduced spatial resolution arterial spin labeling prescan for the rapid measurement of transit delay. Approaches to using the derived transit delay information to optimize and quantify higher resolution continuous arterial spin labeling perfusion images are described. Results in normal volunteers demonstrate heterogeneity of transit delay across different brain regions that lead to quantification errors without the transit maps and demonstrate the feasibility of this approach to perfusion and transit delay quantification.

Cortical hypoperfusion in Parkinson's disease assessed using arterial spin labeled perfusion MRI

Alterations in cerebral perfusion and metabolism in Parkinson's disease have been assessed in several studies, using nuclear imaging techniques and more recently magnetic resonance imaging. However, to date there is no consensus in the literature regarding the extent and the magnitude of these alterations. In this work, arterial spin labeled perfusion MRI was employed to quantify absolute cerebral blood flow in a group of early-to-moderate Parkinson's disease patients and age-matched healthy controls. Perfusion comparisons between the two groups showed that Parkinson's disease is characterized by wide-spread cortical hypoperfusion. Subcortically, hypoperfusion was also found in the caudate nucleus. This pattern of hypoperfusion could be related to cognitive dysfunctions that have been previously observed even at the disease early stages. The present results were obtained by means of whole brain voxel-wise comparisons of absolute perfusion values, using statistical parametric mapping, thus avoiding the potentially biased global mean normalization procedure. In addition, this work demonstrates that between-group comparison of relative perfusion values after global mean normalization, introduced artifactual relative perfusion increases, where absolute perfusion was in fact preserved. This has implications for perfusion studies of other brain disorders.

Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI

Arterial spin labeling (ASL) perfusion MRI is a relatively novel technique that can allow for quantitative measurement of cerebral blood flow (CBF) by using magnetically labeled arterial blood water as an endogenous tracer. Available data on resting CBF in schizophrenia primarily come from invasive and expensive nuclear medicine techniques that are often limited to small samples and yield mixed results. The noninvasive nature of ASL offers promise for larger-scale studies. The utility of this approach was examined in 24 healthy controls and 30 patients with schizophrenia. Differences between groups in quantitative CBF were assessed, as were relationships between CBF and psychiatric symptoms. Group comparisons demonstrated greater CBF for controls in several regions including bilateral precuneus and middle frontal gyrus. Patients showed increased CBF in left putamen/superior corona radiata and right middle temporal gyrus. For patients, greater severity of negative symptoms was associated with reduced CBF in bilateral superior temporal gyrus, cingulate gyrus, and left middle frontal gyrus. Increased severity of positive symptoms was related to both higher CBF in cingulate gyrus and superior frontal gyrus and decreased CBF in precentral gyrus/middle frontal gyrus. These findings support the feasibility and utility of implementing ASL in schizophrenia research and expand upon previous results.

Posterior hypoperfusion in parkinson's disease With and without dementia measured with arterial spin labeling MRI

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD.

Altered cerebral blood flow patterns associated with pathologic worry in the elderly

Generalized anxiety disorder (GAD) is the most prevalent anxiety disorder among the elderly and has high functional and cognitive morbidity. However, late-life GAD is relatively understudied and its functional neuroanatomy is uncharted. Several imaging studies have suggested abnormalities in the cognitive control systems of emotion regulation in anxiety disorders in young adults. The aim of this study was to examine the neural correlates of emotion regulation in late-life GAD. We compared 7 elderly GAD subjects and 10 elderly nonanxious comparison subjects using functional MRI. Regional cerebral blood flow (rCBF) was measured using pulsed arterial spin labeling perfusion MRI at rest and during an emotion regulation paradigm. Relative to the rest condition, elderly nonanxious comparison subjects had increased rCBF during worry induction (WI) in the right insula, bilateral amygdala, and associative temporooccipital areas. Elderly GAD subjects had increased rCBF during WI in the associative temporooccipital areas, but not in the insula or the amygdala. During worry suppression (WS), elderly nonanxious comparison subjects had increased rCBF in the prefrontal cortex (PFC) and dorsal ACC. Elderly GAD subjects had no changes in rCBF during WS in the PFC. When attempting to regulate their emotional responses, elderly anxious subjects failed to activate prefrontal regions involved in the downregulation of negative emotions. These results, showing that elderly anxious subjects are not effectively engaging the PFC in suppressing worry, may be clinically relevant for developing personalized therapeutic strategies for the treatment of late-life GAD.

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

Pharmacological magnetic resonance imaging (phMRI) is increasingly being used in drug discovery and development to speed the translation from the laboratory to the clinic. The two primary methods in phMRI include blood-oxygen-level-dependent (BOLD) contrast and arterial spin-labeled (ASL) perfusion MRI. BOLD contrast has been widely applied in existing phMRI studies. However, because of the lack of absolute quantification and poor reproducibility over time scales longer than hours or across scanning sessions, BOLD fMRI may not be suitable to track oral and other long-term drug effects on baseline brain function. As an alternative method, ASL provides noninvasive, absolute quantification of cerebral blood flow both at rest and during task activation. ASL perfusion measurements have been shown to be highly reproducible over minutes and hours to days and weeks. These two characteristics make ASL an ideal tool for phMRI for studying both intravenous and oral drug action as well as understanding drug effects on baseline brain function and brain activation to cognitive or sensory processing. When ASL is combined with BOLD fMRI, drug-induced changes in cerebral metabolic rate of oxygen may also be inferred. Representative phMRI studies using ASL perfusion MRI on caffeine, remifentanil, and metoclopramide (dopamine antagonist) are reviewed here, with an emphasis on the methodologies used to control for potentially confounding vascular and systemic effects. Both the potentials and limitations of using ASL as an imaging marker of drug action are discussed.

Hypertension and Cerebral Vasoreactivity

Hypertension is associated with microvascular and macrovascular brain injury but its direct influence on the cerebral circulation is not fully clear. Our objective was to investigate the association of hypertension with global and regional cerebral vasoreactivity to CO 2 using continuous arterial spin labeling MRI, independent of stroke and white matter hyperintensities. Participants (n=62; mean age: 66.7±1.0 years, 55% women, 84% white, 65% hypertension, 47% stroke) underwent arterial spin labeling perfusion MRI during normal breathing, 5% CO 2 rebreathing, and hyperventilation, as well as 24-hour ambulatory blood pressure monitoring. Vasoreactivity was the slope of the regression between cerebral perfusion and end-tidal CO 2 . White matter hyperintensity volumes were quantified. Nighttime dipping was calculated as the percentage decline in nighttime/daytime blood pressure. After accounting for stroke and white matter hyperintensity volume, hypertensive participants had lower global vasoreactivity (1.11±0.13 versus 0.43±0.1 mL/100 g per minute per millimeter of mercury; P =0.0012). Regionally, this was significant in the frontal, temporal, and parietal lobes. Higher mean systolic blood pressure was associated with lower vasoreactivity (decreased by 0.11 U/10-mm Hg increase in systolic blood pressure; P =0.04), but nighttime dipping was not ( P =0.2). The magnitude of decrease in vasoreactivity in hypertension without stroke was comparable to the magnitude of decrease in vasoreactivity in stroke without hypertension. Hypertension has a direct negative effect on the cerebrovascular circulation independent of white matter hyperintensities and stroke that is comparable to that seen with stroke. Because lower vasoreactivity is associated with poor outcomes, studies of the impact of antihypertensive on vasoreactivity are important.

Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction?

Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission. In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared. In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task. If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.

Cortical perfusion in alcohol-dependent individuals during short-term abstinence: relationships to resumption of hazardous drinking after treatment

Relapse to hazardous levels of alcohol consumption after treatment for alcohol use disorders is common. Investigation of the neurobiological correlates of resumption of hazardous drinking is necessary to clarify the mechanisms contributing to relapse. Fifty-seven treatment-seeking alcohol-dependent participants (ALC) completed arterial spin labeling perfusion MRI of the frontal and parietal gray matter (GM) at 7 ± 3 days of abstinence (baseline). ALC participants were restudied after 35 ± 11 days of abstinence (assessment point 2: AP2). Twenty-eight nonsmoking, light-drinking control participants (nsLD) from the community were studied with perfusion MRI. ALC participants were followed over 12 months after baseline study and were classified as abstainers (no alcohol consumption; n = 19) and resumers (any alcohol consumption; n = 38) at follow-up. Cross-sectional and longitudinal perfusion was compared in abstainers, resumers, and nsLD. At baseline, resumers demonstrated significantly lower frontal and parietal GM perfusion than nsLD and abstainers. Abstainers and nsLD were not different on frontal or parietal GM perfusion. No significant longitudinal perfusion changes were observed in abstainers and resumers. At AP2, resumers showed significantly lower frontal GM perfusion than nsLD and abstainers, whereas no group differences were observed for parietal GM. Abstainers and nsLD were not different on frontal GM perfusion. The significantly decreased frontal GM perfusion in resumers compared with both abstainers and nsLD across the assessment interval suggests premorbid and/or acquired neurobiological abnormalities of the frontal GM in resumers.