Anoxic injury-associated cerebral hyperperfusion identified with arterial spin-labeled MR imaging

BACKGROUND AND PURPOSE: Anoxic brain injury is a devastating result of prolonged hypoxia. The goal of this study was to use arterial spin-labeling (ASL) to characterize the perfusion patterns encountered after anoxic injury to the brain.MATERIALS AND METHODS: Sixteen patients with a history of anoxic or hypoxic-ischemic injury ranging in age from 1.5 to 78.0 years (mean, 50.3 years) were analyzed with conventional MR imaging and pulsed ASL 1.0–13.0 days (mean, 4.6 days) after anoxic insult. The cerebral perfusion in each case was quantified by using pulsed ASL as part of the standard stroke protocol. Correlation was made among perfusion imaging, conventional imaging, clinical history, laboratory values, and outcome.RESULTS: Fifteen of the 16 patients showed marked global hyperperfusion, and 1 patient showed unilateral marked hyperperfusion. Mean gray matter (GM) cerebral blood flow (CBF) in these patients was 142.6 mL/100 g of tissue per minute (ranging from 79.9 to 204.4 mL/100 g of tissue per minute). Global GM CBF was significantly higher in anoxic injury subjects, compared with age-matched control groups with and without infarction (F_2,39 = 63.11; P < .001). Three patients had global hyperperfusion sparing areas of acute infarction. Conventional imaging showed characteristic restricted diffusion in the basal ganglia (n = 10) and cortex (n = 13). Most patients examined died (n = 12), with only 4 patients surviving at the 4-month follow-up.CONCLUSION: Pulsed ASL can dramatically demonstrate and quantify the severity of the cerebral hyperperfusion after a global anoxic injury. The global hyperperfusion probably results from loss of autoregulation of cerebral vascular resistance.

Anoxic injuries resulting from global cessation of oxygenated cerebral blood flow (CBF) have profound effects on cerebral metabolism. Characteristic imaging findings include infarctions in regions with higher metabolic demands, including the basal ganglia and cerebral cortex.^1–3 Arterial spin-labeling (ASL) perfusion imaging generates qualitative and quantitative data. ASL perfusion imaging findings in these patients have not been described in the literature. Xenon CT perfusion has been used to evaluate postresuscitation patients with mixed results.^4–6 Other cerebral perfusion methods, such as nuclear medicine hexamethylpropyleneamine oxime single-photon emission CT and O-15 positron-emission tomography (PET), rely on differences in regional perfusion and may not detect a global symmetric hyperperfusion pattern.⁷ The goal of this study was to use ASL to characterize the perfusion patterns encountered after anoxic injury to the brain. We present a series of 16 patients with a history of anoxic injury who demonstrated marked cerebral hyperperfusion on pulsed ASL perfusion imaging. We propose that this marked hyperperfusion is secondary to the loss of autoregulation of cerebral vascular resistance caused by the anoxic injury.     

Arterial spin-labeling in routine clinical practice, part 2: hypoperfusion patterns

Arterial spin-labeling (ASL) is a powerful perfusion imaging technique capable of quickly demonstrating both hypo- and hyperperfusion on a global or localized scale in a wide range of disease states. Knowledge of pathophysiologic changes in blood flow and common artifacts inherent to the sequence allows accurate interpretation of ASL when performed as part of a routine clinical imaging protocol. Patterns of hypoperfusion encountered during routine application of ASL perfusion imaging in a large clinical population have not been described. The objective of this review article is to illustrate our experience with a heterogeneous collection of ASL perfusion cases and describe patterns of hypoperfusion. During a period of 1 year, more than 3000 pulsed ASL procedures were performed as a component of routine clinical brain MR imaging evaluation at both 1.5 and 3T. These images were reviewed with respect to image quality and patterns of hypoperfusion in various normal and disease states.     

Arterial spin-labeling in routine clinical practice: a preliminary experience of 200 cases and correlation with MRI and clinical findings

We described our experience with a heterogeneous collection of 200 arterial spin-labeling (ASL) perfusion cases. ASL imaging was performed on a 1.5-T magnetic resonance imaging unit with a receive head coil using a second version of quantitative perfusion imaging. Sixty-four (32%) patients exhibited normal perfusion, 107 (53.5%) patients exhibited hypoperfusion, and 29 (14.5%) exhibited hyperperfusion. This ASL study illustrates the usefulness of ASL perfusion studies in a number of pathological conditions and that perfusion imaging can be implemented successfully in a routine clinical neuroimaging protocol.     

Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain continuous arterial spin labeling perfusion imaging

Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by brain perfusion studies including single photon emission computed tomography and positron emission tomography. In addition, brain perfusion can be studied with arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that quantitatively measures cerebral blood flow per unit tissue mass. We followed up a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling technique, which showed crossed cerebellar hyperperfusion after acute stroke-like episode. This cerebellar hyperperfusion normalized in the follow-up.     

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.     

Arterial spin-labeling perfusion imaging of childhood encephalitis: correlation with seizure and clinical outcome

Purpose

In childhood encephalitis, perfusion abnormalities have been infrequently reported to associate with clinical status. We investigated whether perfusion abnormalities correlated with seizure and clinical outcome in encephalitis.

Methods

We retrospectively analyzed the MR studies of 77 pediatric patients with encephalitis. Pseudo-continuous arterial spin-labeling (ASL) imaging was performed on a 3-T scanner. The patients were divided into five groups according to ASL perfusion imaging pattern: normal perfusion (NP), focal hypoperfusion (Lf), extreme global hypoperfusion (LE), focal hyperperfusion (Hf), and extreme global hyperperfusion (HE). Clinical outcome at 3 weeks was dichotomized to unfavorable or favorable outcome according to the Glasgow outcome scale. Multivariate logistic regression was conducted to predict unfavorable outcome and presence of seizure separately, based on explanatory variables including age, sex, and ASL pattern.

Results

Twenty-seven (35%) patients were designated as in group Hf, five (7%) in group Lf, 11 (14%) in group LE, none in group HE, and 34 (44%) in group NP. Multivariate logistic regression analysis showed that ASL pattern was significantly associated with unfavorable outcome (P?=?0.005) and with presence of seizure (P?=?0.005). For ASL pattern, group LE was 17.31 times as likely to have an unfavorable outcome as group NP (odds ratio confidence interval [CI] 3.084, 97.105; P?=?0.001). Group Hf was 6.383 times as likely to have seizure as group NP (CI 1.765, 23.083; P?=?0.005).

Conclusions

In childhood encephalitis, patients with extreme global hypoperfusion had poor neurological outcome and those with focal hypoperfusion were more likely to have seizure.

     

Acute cerebral vascular accident associated with hyperperfusion.

Cerebral radionuclide angiography can demonstrate decreased or normal radioactivity in the affected region during the arterial phase in patients who have sustained a cerebral vascular accident and thus enhances the diagnostic specificity of the static brain image. In an occasional patient, however, a seemingly paradoxical pattern of regional hyperperfusion with a return to normal or subnormal perfusion following the acute phase has been observed. This phenomenon, called "luxury perfusion," has been defined using intra-arterial 133Xe for semiquantitative cerebral blood flow measurements and should be kept in mind as a potentially misleading cerebral imaging pattern.     

Arterial spin-labeling in routine clinical practice, part 1: technique and artifacts

The routine use of arterial spin-labeling (ASL) in a clinical population has led to the depiction of diverse brain pathologic features. Unique challenges in the acquisition, postprocessing, and analysis of cerebral blood flow (CBF) maps are encountered in such a population, and high-quality ASL CBF maps can be generated consistently with attention to quality control and with the use of a dedicated postprocessing pipeline. Familiarity with commonly encountered artifacts can help avoid pitfalls in the interpretation of CBF maps. The purpose of this review was to describe our experience with a heterogeneous collection of ASL perfusion cases with an emphasis on methodology and common artifacts encountered with the technique. In a period of 1 year, more than 3000 pulsed ASL cases were performed as a component of routine clinical brain MR evaluation at both 1.5 and 3T. These ASL studies were analyzed with respect to overall image quality and patterns of perfusion on final gray-scale DICOM images and color Joint Photographic Experts Group (JPEG) CBF maps, and common artifacts and their impact on final image quality were categorized.     

Brain perfusion territory imaging: methods and clinical applications of selective arterial spin-labeling MR imaging

The ability to visualize perfusion territories in the brain is important for many clinical applications. The aim of this overview is to highlight the possibilities of selective arterial spin-labeling (ASL) magnetic resonance (MR) imaging techniques in the assessment of the perfusion territories of the cerebral arteries. In the past decade, the optimization of selective ASL MR techniques to image the cerebral perfusion territories has resulted in numerous labeling approaches and an increasing number of clinical applications. In this article, the methods and clinical applications of selective ASL MR imaging are described and the importance of perfusion territory information in studying cerebral hemodynamic changes in patients with cerebrovascular disease is shown. In specific patient groups with cerebrovascular disease, such as acute stroke, large artery steno-occlusive disease, and arteriovenous malformation, selective ASL MR imaging provides valuable hemodynamic information when added to current MR protocols. As a noninvasive tool for perfusion territory measurements, selective ASL may contribute to a better understanding of the relation between the vasculature, perfusion, and brain function.     

Migraine associated cerebral hyperperfusion with arterial spin-labeled MR imaging

We present a case series demonstrating abnormal regional cerebral hyperperfusion associated with migraine headache using arterial spin-labeling (ASL). In 3 of 11 patients, regional cortical hyperperfusion was demonstrated during a headache episode that corresponded to previous aura symptoms.     

3D-ASL与DSC-PWI在缺血性脑梗死患者中的对比研究

目的：对比分析磁共振三维动脉自旋标记成像（3D-ASI。）与动态磁敏感对比增强灌注成像（DSC-PWI）在缺血性脑梗死患者中的临床应用价值。方法：32例缺血性脑梗死患者行常规MRI序列、DWI、MRA、3D-ASL及DSC-PWI检查。观察脑梗死患者的3D-ASI.DSC-PwI灌注后处理图像并进行评分（显示有低灌注记为-1,未见明显灌注异常记为0,高灌注记为＋1）,并比较分析ASI-CBF与PWI测量的CBF、CBV、MTT及TTP之间的差异。结果：32例中ASL显示灌注异常者有28（87．5％）例,PWI-CBF、PWI-CBV、PWI-MTT及PWI-TTP异常者分别为18（56．25％）、18（56．25％）、19（59．38％）和21（65．63％）例。McNemar检验结果显示,ASI。与PWI各参量图像所显示的灌注异常概率之间差异有统计学意义（P值分别为0．002、0．002、0．004和0．016）;除去在任意一种灌注图像上显示为高灌注的病例后,ASL-CBF与PWI各参量比较的P值分别为0．008、0．008、0．063和0．125,其中MTT及TTP的差异无统计学意义。结论：作为一种无创性MRI技术,ASL在临床应用中能够较为真实可靠地反映缺血性脑梗死的低灌注状态。     

Perfusion-weighted MR imaging studies in brain hypervascular diseases: comparison of arterial input function extractions for perfusion measurement

BACKGROUND AND PURPOSE: Brain hypervascular diseases are complex and induce hemodynamic disturbances on brain parenchyma, which are difficult to accurately evaluate by using perfusion-weighted (PWI) MR imaging. Our purpose was to test and to assess the best AIF estimation method among 4 patients with brain hypervascular disease and healthy volunteers. METHODS: Thirty-three patients and 10 healthy volunteers underwent brain perfusion studies by using a 1.5T MR imaging scanner with gadolinium-chelate bolus injection. PWI was performed with the indicator dilution method. AIF estimation methods were performed with local, regional, regional scaled, and global estimated arterial input function (AIF), and PWI measurements (cerebral blood volume [CBV] and cerebral blood flow [CBF]) were performed with regions of interest drawn on the thalami and centrum semiovale in all subjects, remote from the brain hypervascular disease nidus. Abnormal PWI results were assessed by using Z Score, and evaluation of the best AIF estimation method was performed by using a no gold standard evaluation method. RESULTS: From 88% to 97% of patients had overall abnormal perfusion areas of hypo- (decreased CBV and CBF) and/or hyperperfusion (increased CBV and CBF) and/or venous congestion (increased CBV, normal or decreased CBF), depending on the AIF estimation method used for PWI computations. No gold standard evaluation of the 4 AIF estimates found the regional and the regional scaled methods to be the most accurate. CONCLUSION: Brain hypervascular disease induces remote brain perfusion abnormalities that can be better detected by using PWI with regional or regional scaled AIF estimation methods.     

Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.     

Crossed cerebellar hyperperfusion in patients with seizure-related cerebral cortical lesions: an evaluation with arterial spin labelling perfusion MR imaging

Purpose

Crossed cerebellar (CC) diaschisis refers to a decrease in cerebellar perfusion in the presence of contralateral supratentorial lesions. Most of the previous studies have examined stroke patients. In contrast to strokes, seizure-related cerebral cortical lesions (SCCLs) usually show hyperperfusion, and therefore, cerebellar perfusion patterns are expected to be different from those of strokes. With arterial spin labelling (ASL), we evaluated the cerebellar perfusion status in patients with SCCLs.

Materials and methods

Using a search of the recent database over the last 31 months, 26 patients were enrolled in this study. The inclusion criteria were as follows: (1) a history of seizures, (2) MR examination taken within 24 h from the last seizure, (3) the presence of SCCLs on T2/FLAIR or DWI, (4) hyperperfusion in the corresponding areas of SCCLs on ASL, and (5) no structural abnormality in the cerebellum. The perfusion status in the contralateral cerebellum was evaluated and categorized as hyper-, iso- and hypoperfusion. The asymmetric index (AI) of cerebellar perfusion was calculated by ROI measurement of the signal intensity on ASL.

Results

The mean time between the last seizure and MR examinations was 5 h 30 min. CC hyperperfusion was observed in 17 patients (65.4%), hypoperfusion in 7 (26.9%) and isoperfusion in 2 (7.7%). Regarding the location of SCCLs, CC hyperperfusion was more frequent (71.4 vs. 58.3%), and the mean AI was higher (42.0 vs. 11.5) when the lesion involved the frontal lobe.

Conclusions

In patients with SCCLs, CC hyperperfusion occurred more often than hypo- and isoperfusion, especially when the lesions involved the frontal lobe.

     

Quantification of regional pulmonary blood flow using ASL-FAIRER.

Pulsed arterial spin labeling (ASL) techniques have been theoretically and experimentally validated for cerebral blood flow (CBF) quantification. In this study ASL-FAIRER was used to measure regional pulmonary blood flow (rPBF) in seven healthy subjects. Two general ASL strategies were investigated: 1) a single-subtraction approach using one tag-control pair acquisition at an inversion time (TI) matched to the RR-interval, and 2) a multiple-subtraction approach using tag-control pairs acquired at various TIs. The mean rPBF averaged 1.70 +/- 0.38 ml/min/ml when measured with the multiple-subtraction approach, and was approximately 2% less when measured with the single-subtraction method (1.66 +/- 0.24 ml/min/ml). Assuming an average lung density of 0.33 g/ml, this translates into a regional perfusion of approximately 5.5 ml/g/min, which is comparable to other measures of pulmonary perfusion. As with other ASL applications, a key problem with quantitative interpretation of the results is the physical gap between the tagging region and imaged slice. Because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. The advantages and drawbacks of the single- vs. multiple-subtraction approaches are considered within a theoretical framework tailored to PBF.     

Pseudo-continuous arterial spin labeling at very high magnetic field (11.75 T) for high-resolution mouse brain perfusion imaging

With the increasing number of transgenic mouse models of human brain diseases, there is a need for a sensitive method that allows assessing quantitative whole brain perfusion within a reasonable scan time. Arterial spin labeling (ASL), an MRI technique that permits the noninvasive quantification of cerebral blood flow, has been used to assess rodents brain perfusion. For mice, the reported experiments performed with continuous or pulsed ASL were challenged by poor multislice capability, limited sensitivity, or quantification issues. Here, the recently proposed pseudo-continuous ASL strategy, which has shown great promise for human studies, was investigated for mouse brain perfusion imaging at 11.75 T. Pseudo-continuous ASL was experimentally optimized and compared with a standard flow-sensitive alternating inversion recovery sequence for sensitivity, robustness, absolute quantification, and multislice imaging capability. A sensitivity gain up to 40% and clear advantages for multislice imaging are obtained with pseudo-continuous ASL.     

Human brain: reliability and reproducibility of pulsed arterial spin-labeling perfusion MR imaging

The Committee of Human Research of the University of California San Francisco approved this study, and all volunteers provided written informed consent. The goal of this study was to prospectively determine the global and regional reliability and reproducibility of noninvasive brain perfusion measurements obtained with different pulsed arterial spin-labeling (ASL) magnetic resonance (MR) imaging methods and to determine the extent to which within-subject variability and random noise limit reliability and reproducibility. Thirteen healthy volunteers were examined twice within 2 hours. The pulsed ASL methods compared in this study differ mainly with regard to magnetization transfer and eddy current effects. There were two main results: (a) Pulsed ASL MR imaging consistently had high measurement reliability (intraclass correlation coefficients greater than 0.75) and reproducibility (coefficients of variation less than 8.5%), and (b) random noise rather than within-subject variability limited reliability and reproducibility. It was concluded that low signal-to-noise ratios substantially limit the reliability and reproducibility of perfusion measurements.     

Intracranial 3D and 4D MR Angiography Using Arterial Spin Labeling: Technical Considerations

In the 1980’s some of the earliest studies of arterial spin labeling (ASL) MRI have demonstrated its ability to generate MR angiography (MRA) images. Thanks to many technical improvements, ASL has been successfully moving its position from the realm of research into the clinical area, albeit more known as perfusion imaging than as MRA. For MRA imaging, other techniques such as time-of-flight, phase contrast MRA and contrast-enhanced (CE) MRA are more popular choices for clinical applications. In the last decade, however, ASL-MRA has been experiencing a remarkable revival, especially because of its non-invasive nature, i.e. the fact that it does not rely on the use of contrast agent. Very importantly, there are additional benefits of using ASL for MRA. For example, its higher flexibility to achieve both high spatial and temporal resolution than CE dynamic MRA, and the capability of vessel specific visualization, in which the vascular tree arising from a selected artery can be exclusively visualized. In this article, the implementation and recent developments of ASL-based MRA are discussed; not only focusing on the basic sequences based upon pulsed ASL or pseudo-continuous ASL, but also including more recent labeling approaches, such as vessel-selective labeling, velocity-selective ASL, vessel-encoded ASL and time-encoded ASL. Although these ASL techniques have been already utilized in perfusion imaging and their usefulness has been suggested by many studies, some additional considerations should be made when employing them for MRA, since there is something more than the difference of the spatial resolution of the readout sequence. Moreover, extensive discussion is included on what readout sequence to use, especially by highlighting how to achieve high spatial resolution while keeping scan-time reasonable such that the ASL-MRA sequence can easily be included into a clinical examination.     

Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements.

Arterial spin labeling (ASL) can be used to measure perfusion without the use of contrast agents. Due to the small volume fraction of blood vessels compared to tissue in the human brain (typ. 3-5%) ASL techniques have an intrinsically low signal-to-noise ratio (SNR). In this publication, evidence is presented that the SNR can be improved by using arterial spin labeling in combination with single-shot 3D readout techniques. Specifically, a single-shot 3D-GRASE sequence is presented, which yields a 2.8-fold increase in SNR compared to 2D EPI at the same nominal resolution. Up to 18 slices can be acquired in 2 min with an SNR of 10 or more for gray matter perfusion. A method is proposed to increase the reliability of perfusion quantification using QUIPSS II derivates by acquiring low-resolution maps of the bolus arrival time, which allows differentiation between lack of perfusion and delayed arrival of the labeled blood. For arterial spin labeling, single-shot 3D imaging techniques are optimal in terms of efficiency and might prove beneficial to improve reliability of perfusion quantitation in a clinical setup.     

Strategies for reducing respiratory motion artifacts in renal perfusion imaging with arterial spin labeling

Arterial spin labeling (ASL) perfusion measurements may have many applications outside the brain. In the abdomen, severe image artifacts can arise from motions between acquisitions of multiple signal averages in ASL, even with single‐shot image acquisition. Background suppression and respiratory motion synchronization techniques can be used to ameliorate these artifacts. Two separate in vivo studies of renal perfusion imaging using pulsed continuous ASL (pCASL) were performed. The first study assessed various combinations of background suppression and breathing strategies. The second investigated the retrospective sorting of images acquired during free breathing based on respiratory position. Quantitative assessments of the test‐retest repeatability of perfusion measurements and the image quality scored by two radiologists were made. Image quality was most significantly improved by using background suppression schemes and controlled breathing when compared to other combinations without background suppression or with free breathing, assessed by test‐retests (5% level, F‐test), and by radiologists' scores (5% level, Mann‐Whitney U‐test). Under free breathing, retrospectively sorting images based on respiratory position showed significant improvement. Both radiologists found 100% of the images had preferable image sharpness after sorting. High‐quality renal perfusion measurements with reduced respiratory motion artifacts have been demonstrated using ASL when appropriate background suppression and breathing strategies are applied. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.