Yufen Chen

Applications of Arterial Spin Labeled MRI in the Brain

Perfusion provides oxygen and nutrients to tissues and is closely tied to tissue function while disorders of perfusion are major sources of medical morbidity and mortality. It has been almost two decades since the use of arterial spin labeling (ASL) for noninvasive perfusion imaging was first reported. While initial ASL magnetic resonance imaging (MRI) studies focused primarily on technological development and validation, a number of robust ASL implementations have emerged, and ASL MRI is now also available commercially on several platforms. As a result, basic science and clinical applications of ASL MRI have begun to proliferate. Although ASL MRI can be carried out in any organ, most studies to date have focused on the brain. This review covers selected research and clinical applications of ASL MRI in the brain to illustrate its potential in both neuroscience research and clinical care. J. Magn. Reson. Imaging 2012;35:1026‐1037.

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

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Test-retest reliability of arterial spin labeling with common labeling strategies.

To compare the test–retest reproducibility of three variants of arterial spin labeling (ASL): pseudo‐continuous (pCASL), pulsed (PASL) and continuous (CASL).

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease

The utility of fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging in Alzheimers disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL‐MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG‐PET.

Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: Evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm

A novel approach for quantifying cerebral blood flow (CBF) is proposed that combines the bookend technique of calculating cerebral perfusion with an automatic postprocessing algorithm. The reproducibility of the quantitative CBF (qCBF) measurement in healthy controls (N = 8) showed a higher intraclass correlation coefficient (ICC) and lower coefficient of variation (COV) when calculated with automatic analysis (ICC/COV = 0.90/0.09) than when compared to conventional manual analysis (ICC/COV = 0.58/0.19). Also, the reproducibility in patients (N = 25) was successfully evaluated with the automatic analysis (ICC/COV = 0.81/0.14). In 175 consecutive clinical scans, we found 3.0% and 7.4% of qCBF decrease per decade in white matter (WM) (21.5 ± 6.66 ml/100 g‐min) and gray matter (GM) (49.6 ± 16.2 ml/100 g‐min), respectively. Cerebral blood volume (CBV) showed a significant 3.7% decrease per decade in GM (3.00 ± 0.94 ml/100 g) but not in WM (1.69 ± 0.40 ml/100 g). Mean transit time (MTT) increased by 1.9% and 3.8% per decade in WM (5.04 ± 0.88 s) and GM (4.14 ± 0.80 s), respectively. qCBF and MTT values between males (N = 85) and females (N = 90) were significantly different in GM. Women showed 11% higher qCBF as well as a higher decrease in qCBF with increasing age than men in the whole brain (WB). Our results supported the notion that population average empirical quantification of cerebral perfusion is subject to individual variation as well as age‐ and gender‐dependent variability. Magn Reson Med, 2007.

Caffeine’s effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism

The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO(2)) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO(2). The present study used the calibrated BOLD approach with 5% CO(2) to determine if a 2.5 mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO(2) during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO(2) coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO(2). These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine.

Caffeine dose effect on activation-induced BOLD and CBF responses

Caffeine is a popular psychostimulant, typically found in beverages. While low to intermediate doses of caffeine are associated with positive feelings and increased mental performance and alertness, high doses induce negative feelings such as insomnia, anxiety and nervousness. We investigate if this nonlinear dose-response is present for caffeines effects on functional activation. Twenty-seven healthy subjects were assigned randomly to four different groups: saline, 1 mg/kg, 2.5 mg/kg and 5 mg/kg doses of caffeine. Simultaneous ASL/BOLD timeseries were collected both before and after an intravenous infusion of saline or caffeine and the task-induced CBF and BOLD percent changes were compared. The maximum increase in BOLD response was associated with the intermediate caffeine dose of 2.5 mg/kg, which increased BOLD response by 32.2% and 32.5% in motor and visual areas respectively. The maximum increase in CBF response was associated with the highest caffeine dose of 5 mg/kg. This difference could be related to a different density of A(1) and A(2A) adenosine receptors in the brain.

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.

Quantification of Cerebral Blood Flow as Biomarker of Drug Effect: Arterial Spin Labeling phMRI After a Single Dose of Oral Citalopram

Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood flow (CBF), which can be used as a biomarker of drug effects in pharmacological magnetic resonance imaging (phMRI). In a double‐blind, placebo‐controlled crossover study, we investigated the effects of a single oral dose of citalopram (20 mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support‐vector machine (SVM) analysis detected significant drug‐induced reduction in CBF in brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal cortex. These regions have been shown to have abnormally elevated CBF in patients with major depression, as well as in subjects genetically prone to depression. Mixed‐effects analysis on data extracted from selected regions of interest (ROIs) revealed significant drug effect only in serotonergic areas of the brain (z = −4.45, P < 0.005). These results demonstrate the utility of ASL phMRI as a biomarker of pharmacological activity of orally administered drugs in the brain.

Muscle-fat MRI: 1.5 Tesla and 3.0 Tesla versus histology.

Introduction: We evaluated muscle/fat fraction (MFF) accuracy and reliability measured with an MR imaging technique at 1.5 Tesla (T) and 3.0T scanner strengths, using biopsy as reference. Methods: MRI was performed on muscle samples from pig and rabbit species (n = 8) at 1.5T and 3.0T. A chemical shift based 2‐point Dixon method was used, collecting in‐phase and out‐of‐phase data for fat/water of muscle samples. Values were compared with MFFs calculated from histology. Results: No significant difference was found between 1.5T and 3.0T (P values = 0.41–0.96), or between histology and imaging (P = 0.83) for any muscle tested. Conclusions: Results suggest that a 2‐point Dixon fat/water separation MRI technique may provide reliable quantification of MFFs at varying field strengths across different animal species, and consistency was established with biopsy. The results set a foundation for larger scale investigation of quantifying muscle fat in neuromuscular disorders. Muscle Nerve 50:170–176, 2014