动脉自旋标记技术在阿尔茨海默病中的应用进展

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Arterial spin labeling: Clinical applications

Arterial spin labeling (ASL) is a magnetic resonance imaging perfusion technique that enables quantification of cerebral blood flow (CBF) without the use of intravenous gadolinium contrast. An understanding of the technical basis of ASL and physiologic variations in perfusion are important for recognizing normal variants and artifacts. Pathologic variations in perfusion can be seen in a number of disorders including acute and chronic ischemia, vasculopathy, vascular malformations, tumors, trauma, infection/inflammation, epilepsy and dementia.     

Quantitative perfusion imaging using arterial spin labeling.

Arterial spine labeling (ASL) techniques have matured to the point that they can provide robust quantitative multislice measurements of cerebral blood flow (CBF) under most circumstances. These techniques provide better spatial and temporal resolution than positron-emission tomography (PET) and are entirely noninvasive, requiring no injections or radiation. The most obvious clinical application is in the evaluation of acute stroke, in which the primary pathology is a lack of CBF, precisely the quantity that is measured directly by ASL. The one major technical challenge that currently prevents more general application in the brain is the sensitivity to abnormally long transit delays.     

Differences in cortical perfusion detected by arterial spin labeling in nonamnestic and amnestic subtypes of early-onset Alzheimer's disease

ObjectivesEarly-onset Alzheimer's disease (EOAD) begins before the age of 65 and is characterized by a faster clinical course and the frequency of nonamnestic symptoms compared to late onset Alzheimer disease (LOAD). However, the pathophysiological process of EOAD remains unclear. We expected that ASL may show widespread cortical hypoperfusion in EOAD compared to LOAD and in nonamnestic EOAD compared to amnestic EOAD.MethodsIn this study, 26 EOAD patients (16 amnestic and 10 nonamnestic patients), 29 LOAD patients and 12 healthy controls underwent pseudo-continuous ASL and 3D FFE T1 sequences. Statistical comparisons between EOAD, LOAD and control groups were made after surface-based analysis of CBF maps in regressing out the cortical thickness.ResultsASL showed a more severe hypoperfusion in nonamnestic EOAD patients compared to amnestic EOAD ones, with mean CBF values (± std) of 26.9 (± 3.8) and 46.6 (± 24.1) mL/100 g/min respectively (P = 0.014), located in the bilateral temporo-parietal neocortex, the precuneus, the posterior cingulate cortices (PCC) and frontal lobes. Comparison between EOAD and LOAD patients showed a trend to hypoperfusion in the left parietal lobe, PCC and precuneus in EOAD (P < 0.001 uncorrected).ConclusionsDifferent patterns of hypoperfusion between nonamnestic and amnestic EOAD subtypes were identified, with a more severe and extensive hypoperfusion in nonamnestic patients. A trend towards more severe hypoperfusion was detected in EOAD compared to LOAD. Further studies are needed to validate ASL as a potential tool for the distinction of EOAD subtypes and the prediction of the time course of the disease.     

Vascular disorders: insights from arterial spin labeling

The introduction of high-field magnetic imaging (≥3 T) has made noninvasive arterial spin labeling (ASL) a realistic clinical option for perfusion assessment in vascular disorders. Combined with the advances provided by territorial imaging of individual intracerebral arteries and the measurement of vascular reactivity, ASL is a powerful tool for evaluating vascular diseases of the brain. This article evaluates its use in chronic cerebrovascular disease, stroke, moyamoya disease, and arteriovenous malformation, but ASL may also find applications in related diseases such as vascular dementia.     

Pediatric perfusion MR imaging using arterial spin labeling

Cerebral blood flow (CBF, cerebral perfusion) mirrors cerebral metabolic demand and neuronal function, and therefore, is a vital parameter in the evaluation of pediatric brain injury and recovery. Until recently, measurement of CBF involved intravenous bolus injection of contrast agents or nuclear medicine methods that were technically difficult or ethically problematic in pediatrics. The development of arterial spin label (ASL) perfusion MR imaging as a noninvasive method for measuring CBF allows for the increased ability to measure this vital physiologic parameter in any age group. This article presents the technical aspects of performing ASL perfusion MR imaging in pediatrics, and discusses its current use in clinical studies and its potential for influencing important management strategies in specific disease entities.     

Motor asymmetry related cerebral perfusion patterns in Parkinson's disease: An arterial spin labeling study

Persisting asymmetry of motor symptoms are characteristic of Parkinson''s disease (PD). We investigated the possible lateralized effects on regional cerebral blood flow (CBF), CBF‐connectivity, and laterality index (LI) among PD subtypes using arterial spin labeling (ASL). Forty‐four left‐sided symptom dominance patients (PDL), forty‐eight right‐sided symptom dominance patients (PDR), and forty‐five matched HCs were included. Group comparisons were performed for the regional normalized CBF, CBF‐connectivity and LI of basal ganglia (BA) subregions. The PDL patients had lower CBF in right calcarine sulcus and right supramarginal gyrus compared to the PDR and the HC subjects. Regional perfusion alterations seemed more extensive in the PDL than in the PDR group. In the PDL, correlations were identified between right thalamus and motor severity, between right fusiform gyrus and global cognitive performance. None of correlations survived after multiple comparisons correction. The significantly altered CBF‐connectivity among the three groups included: unilateral putamen, unilateral globus pallidus, and right thalamus. LI score in the putamen was significantly different among groups. Motor‐symptom laterality in PD may exhibit asymmetric regional and interregional abnormalities of CBF properties, particularly in PDL patients. This preliminary study underlines the necessity of classifying PD subgroups based on asymmetric motor symptoms and the potential application of CBF properties underlying neuropathology in PD.     

Multivariate and univariate analysis of continuous arterial spin labeling perfusion MRI in Alzheimer's disease.

Continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI) was combined with multivariate analysis for detection of an Alzheimer's disease (AD)-related cerebral blood flow (CBF) covariance pattern. Whole-brain resting CBF maps were obtained using spin echo, echo planar imaging (SE-EPI) CASL in patients with mild AD (n=12, age=70.7+/-8.7 years, 7 males, modified Mini-Mental State Examination (mMMS)=38.7/57+/-11.1) and age-matched healthy controls (HC) (n=20; age=72.1+/-6.5 years, 8 males). A covariance pattern for which the mean expression was significantly higher (P<0.0005) in AD than in HC was identified containing posterior cingulate, superior temporal, parahippocampal, and fusiform gyri, as well as thalamus, insula, and hippocampus. The results from this analysis were supplemented with those from the more standard, region of interest (ROI) and voxelwise, univariate techniques. All ROIs (17/hemisphere) showed significant decrease in CBF in AD (P<0.001 for all ROIs, alphacorrected=0.05). The area under the ROC curve for discriminating AD versus HC was 0.97 and 0.94 for covariance pattern and gray matter ROI, respectively. Fewer areas of depressed CBF in AD were detected using voxelwise analysis (corrected, P<0.05). These areas were superior temporal, cingulate, middle temporal, fusiform gyri, as well as inferior parietal lobule and precuneus. When tested on extensive split-half analysis to map out the replicability of both multivariate and univariate approaches, the expression of the pattern from multivariate analysis was superior to that of the univariate.     

Tonotopic maps in human auditory cortex using arterial spin labeling

A tonotopic organization of the human auditory cortex (AC) has been reliably found by neuroimaging studies. However, a full characterization and parcellation of the AC is still lacking. In this study, we employed pseudo‐continuous arterial spin labeling (pCASL) to map tonotopy and voice selective regions using, for the first time, cerebral blood flow (CBF). We demonstrated the feasibility of CBF‐based tonotopy and found a good agreement with BOLD signal‐based tonotopy, despite the lower contrast‐to‐noise ratio of CBF. Quantitative perfusion mapping of baseline CBF showed a region of high perfusion centered on Heschl's gyrus and corresponding to the main high‐low‐high frequency gradients, co‐located to the presumed primary auditory core and suggesting baseline CBF as a novel marker for AC parcellation. Furthermore, susceptibility weighted imaging was employed to investigate the tissue specificity of CBF and BOLD signal and the possible venous bias of BOLD‐based tonotopy. For BOLD only active voxels, we found a higher percentage of vein contamination than for CBF only active voxels. Taken together, we demonstrated that both baseline and stimulus‐induced CBF is an alternative fMRI approach to the standard BOLD signal to study auditory processing and delineate the functional organization of the auditory cortex. Hum Brain Mapp 38:1140–1154, 2017. © 2016 Wiley Periodicals, Inc.     

Cerebral blood flow quantification using vessel-encoded arterial spin labeling

Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.     

Regional variation of cerebral blood flow and arterial transit time in the normal and hypoperfused rat brain measured using continuous arterial spin labeling MRI.

Continuous arterial spin labeling (CASL) is a noninvasive magnetic resonance (MR) method for measuring cerebral perfusion. In its most widely used form, CASL incorporates a postlabeling delay to minimize the sensitivity of the technique to transit time effects, which otherwise corrupt cerebral blood flow (CBF) quantification. For this delay to work effectively, it must be longer than the longest transit time present in the system. In this work, CASL measurements were made in four coronal slices in the rat brain using a range of postlabeling delays. By doing this, direct estimation of both CBF and arterial transit time (delta(a)) was possible. These measurements were performed in the normal brain and during hypoperfusion induced by occlusion of the common carotid arteries. It was found that, in the normal rat brain, significant regional variation exists for both CBF and delta(a). Mean values of CBF and delta(a) in the selected gray matter regions of interest were 233 mL/100 g min and 266 ms, respectively, with the latter ranging from 100 to 500 ms. Therefore, use of a 500-ms postlabeling delay is suitable for any location in the normal rat brain. After common carotid artery occlusion, CBF decreased and delta(a) increased by regionally dependent amounts. In the sensory cortex, delta(a) increased to a mean value of 740 ms, significantly greater than 500 ms. These results highlight the importance of either (a) determining delta(a) as part of the CASL measurement or (b) knowing the approximate range of values delta(a) is likely to take for a given application, so that the parameters of the CASL sequence can be chosen appropriately.     

Multidelay multiparametric arterial spin labeling perfusion MRI and mild cognitive impairment in early stage Parkinson's disease

Mild cognitive impairment (MCI), a well‐defined nonmotor manifestation of Parkinson's disease (PD), greatly impairs functioning and quality of life. However, the contribution of cerebral perfusion, quantified by arterial spin labeling (ASL), to MCI in PD remains poorly understood. The selection of an optimal delay time is difficult for single‐delay ASL, a problem which is avoided by multidelay ASL. This study uses a multidelay multiparametric ASL to investigate cerebral perfusion including cerebral blood flow (CBF) and arterial transit time (ATT) in early stage PD patients exhibiting MCI using a voxel‐based brain analysis. Magnetic resonance imaging data were acquired on a 3.0 T system at rest in 39 early stage PD patients either with MCI (PD‐MCI, N = 22) or with normal cognition (PD‐N, N = 17), and 36 age‐ and gender‐matched healthy controls (HCs). CBF and ATT were compared among the three groups with SPM using analysis of variance followed by post hoc analyses to define regional differences and examine their relationship to clinical data. PD‐MCI showed prolonged ATT in right thalamus compared to both PD‐N and HC, and in right supramarginal gyrus compared to HC. PD‐N showed shorter ATT in left superior frontal cortex compared to HC. Prolonged ATT in right thalamus was negatively correlated with the category fluency test (p = .027, r = ?0.495) in the PD‐MCI group. This study shows that ATT may be a more sensitive marker than CBF for the MCI, and highlights the potential role of thalamus and inferior parietal region for MCI in early stage PD.     

Feasibility of velocity selective arterial spin labeling in functional MRI.

Arterial spin labeling (ASL) magnetically inverts or saturates the spins in arterial blood and uses them as endogenous tracers. Conventionally, the tagging band is upstream or nonselective to the target slices. In the brain, ASL-based functional magnetic resonance imaging (fMRI) has been shown to detect activation better localized in gray matter than blood oxygenation level dependent contrast. More recently, velocity selective-ASL (VS-ASL) was proposed to tag spins according to their flow velocity. One desirable characteristic of VS-ASL is its capability to generate tags sufficiently close to the target slices and thereby circumvent the complication of non-zero transit delay. In this study, we investigate the feasibility of VS-ASL in fMRI by comparing it with a conventional ASL method (PICORE). The results from the visual cortex of healthy volunteers show that VS-ASL and PICORE have comparable spatial specificity in detecting the flow change induced by neuronal activity. Velocity selective-arterial spin labeling can further distinguish the contribution from different flow directions but spurious elevation of fractional signal change may occur when the VS tagging is applied off the direction of blood supply. The flow reaches the vicinity of perfusion at a cutoff velocity (Vc) of 2 cm/sec whereas the activation exclusively detected by Vc=4 cm/sec implies the arteriolar response to the neuronal activity and a respondent vessel diameter up to 240 microm. Velocity selective imaging can remove intravascular signal from the vessels where the flow velocity is above Vc.     

Pulsed arterial spin labeling applications in brain tumors: practical review

Few institutions use MRI perfusion without contrast injection called arterial spins labeling (ASL) routinely in clinical setting. After general considerations concerning the different ASL techniques and quantitative issues, we will detail a pulsed sequence that can be used on a clinical 1.5-T MR unit. We will discuss and illustrate the use of ASL in tumoral diseases for diagnosis, gliomas grading, stereotactic biopsy guidance and for follow-up after treatment.