Arterial Transit Time Mapping Obtained by Pulsed Continuous 3D ASL Imaging with Multiple Post-Label Delay Acquisitions: Comparative Study with PET-CBF in Patients with Chronic Occlusive Cerebrovascular Disease.
ABSTRACT: Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O-water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 ± 0.08, slope: 0.87 ± 0.22, intercept: 6.1 ± 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 ± 0.41 sec and 1.12 ± 0.30 sec, respectively, p <0.0005). CBF measurement using pCASL with delay compensation was feasible and fairly accurate even in altered hemodynamic states.
Project description:Background:Distinguishing moyamoya disease (MMD) from intracranial atherosclerotic stenosis (IAS) is critical for its treatment and outcome evaluation. This study aimed to use the combined sequences of high-resolution magnetic resonance imaging (HRMRI) and arterial spin labeling MR (ASL-MR) to identify the two entities accurately. Methods:This prospective study enrolled 58 patients with middle cerebral artery (MCA) steno-occlusion identified by digital subtraction angiography (DSA), including 27 cases of MMD and 31 cases of IAS. All patients underwent MRA, HRMRI and ASL-MR prior to DSA. Two radiologists blinded to DSA results analyzed the MR images. The inner and outer diameters of the target arteries, the wall thickness of the stenotic segment, and the perfusion status in the territories of the target arteries [cerebral blood flow (CBF), cerebral blood volume (CBV) and arterial transit time (ATT)] were measured quantitatively. The differences between MMD and IAS regarding the aspects of HRMRI and Pseudo-continuous ASLMR (PCASL-MR) maps were analyzed based on both visual characteristics and data information. Results:Regarding the HRMRI images, MMD tended to have homogeneous and concentric vessel-wall thickening as well as collaterals adjacent to the stenotic vessels; while IAS showed eccentric and heterogeneous vessel-wall thickening. For the CBF maps of PCASL-MR, abnormal hyper-perfused spots embedded inside the hypo-perfused regions were observed in MMD instead of IAS. Quantitative analysis revealed that MMD displayed smaller inner and outer diameters, and smaller maximum wall thickness, higher average value of CBF, CBV and ATT, and higher maximum value of CBF and CBV, when compared to IAS (all P<0.01). The average wall thickness and the maximum value of ATT showed no significant difference between MMD and IAS (P>0.01). Conclusions:HRMRI combined with PCASL-MR may help distinguish MMD and IAS induced cerebral arterial stenosis and cerebral perfusion disorder accurately and non-invasively.
Project description:The purpose of the present study was to present a multi-delay multi-parametric pseudo-continuous arterial spin labeling (pCASL) protocol with background suppressed 3D GRASE (gradient and spin echo) readout for perfusion imaging in acute ischemic stroke. PCASL data at 4 post-labeling delay times (PLD = 1.5, 2, 2.5, 3 s) were acquired within 4.5 min in 24 patients (mean age 79.7 ± 11.4 years; 11 men) with acute middle cerebral artery (MCA) stroke who also underwent dynamic susceptibility contrast (DSC) enhanced perfusion imaging. Arterial transit times (ATT) were estimated through the calculation of weighted delays across the 4 PLDs, which were included in the calculation of cerebral blood flow (CBF) and arterial cerebral blood volume (CBV). Mean perfusion parameters derived using pCASL and DSC were measured within MCA territories and infarct regions identified on diffusion weighted MRI. The results showed highly significant correlations between pCASL and DSC CBF measurements (r > = 0.70, p < = 0.0001) and moderately significant correlations between pCASL and DSC CBV measurements (r > = 0.45, p < = 0.027) in both MCA territories and infarct regions. ASL ATT showed correlations with DSC time to the maximum of tissue residual function (Tmax)(r = 0.66, p = 0.0005) and mean transit time (MTT)(r = 0.59, p = 0.0023) in leptomeningeal MCA territories. The present study demonstrated the feasibility for noninvasive multi-parametric perfusion imaging using ASL for acute stroke imaging.
Project description:Until recently, no direct comparison between [(15)O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [(15)O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [(15)O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3±6.1?mL and 51.9±7.1?mL per 100?g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [(15)O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.
Project description:OBJECTIVES:To present a multi-delay pseudo-continuous ASL (pCASL) protocol that offers simultaneous measurements of cerebral blood flow (CBF) and arterial transit time (ATT), and to study correlations between multi-delay pCASL and CT perfusion in moyamoya disease. METHODS:A 4 post-labeling delay (PLD) pCASL protocol was applied on 17 patients with moyamoya disease who also underwent CT perfusion imaging. ATT was estimated using the multi-delay protocol and included in the calculation of CBF. ASL and CT perfusion images were rated for lesion severity/conspicuity. Pearson correlation coefficients were calculated across voxels between the two modalities in grey and white matter of each subject respectively and between normalized mean values of ASL and CT perfusion measures in major vascular territories. RESULTS:Significant associations between ASL and CT perfusion were detected using subjective ratings, voxel-wise analysis in grey and white matter and region of interest (ROI)-based analysis of normalized mean perfusion. The correlation between ASL CBF and CT perfusion was improved using the multi-delay pCASL protocol compared to CBF acquired at a single PLD of 2 s (P?<?0.05). CONCLUSIONS:There is a correlation between perfusion data from ASL and CT perfusion imaging in patients with moyamoya disease. Multi-delay ASL can improve CBF quantification, which could be a prognostic imaging biomarker in patients with moyamoya disease. KEY POINTS:• Simultaneous measurements of CBF and ATT can be achieved using multi-delay pCASL. • Multi-delay ASL was compared with CT perfusion in patients with moyamoya disease. • Statistical analyses showed significant associations between multi-delay ASL and CT perfusion. • Multi-delay ASL can improve CBF quantification in moyamoya disease.
Project description:Pseudo-continuous arterial spin labeling (pCASL) is a completely non-invasive method of cerebral perfusion measurement. However, cerebral blood flow (CBF) quantification is hampered by arterial transit artifacts characterized by bright vascular signals surrounded by decreased signals in tissue regions, which commonly appear in patients with reduced cerebral perfusion pressure. The spatial coefficient of variation (CoV) of pCASL CBF images has been proposed as an alternative region-of-interest (ROI)-based hemodynamic measure to predict prolonged arterial transit time (ATT). This retrospective study investigates the utility of spatial CoV by comparison with 15O positron emission tomography (PET). For patients with cerebrovascular steno-occlusive disease ( n?=?17), spatial CoV was positively correlated with ATT independently measured by pulsed arterial spin labeling ( r?=?0.597, p?<?0.001), confirming its role as an ATT-like hemodynamic measure. Comparisons with 15O PET demonstrated that spatial CoV was positively correlated with vascular mean transit time ( r?=?0.587, p?<?0.001) and negatively correlated with both resting CBF ( r?=?-0.541, p?=?0.001) and CBF response to hypercapnia ( r?=?-0.373, p?=?0.030). ROI-based spatial CoV calculated from single time-point pCASL can potentially detect subtle perfusion abnormalities in clinical settings.
Project description:PURPOSE:To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL). METHODS:A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV). RESULTS:The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL. CONCLUSION:Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT.
Project description:PURPOSE:Cerebral blood flow (CBF) and glucose metabolism are important and significant factors in ischaemic cerebrovascular disease. The objective of this study was to use quantitative hybrid PET/MR to evaluate the effects of surgery treatment on the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease. METHODS:Fifteen patients diagnosed with ischaemic cerebrovascular disease were evaluated using a hybrid TOF PET/MR system (Signa, GE Healthcare). The CBF value measured by arterial spin labelling (ASL) and the standardized uptake value ratio (SUVR) measured by 18F-FDG PET were obtained, except for the infarct area and its contralateral side, before and after bypass surgery. The asymmetry index (AI) was calculated from the CBF and SUVR of the ipsilateral and contralateral cerebral hemispheres, respectively. The ?CBF and ?SUVR were calculated as the percent changes of CBF and SUVR between before and after surgery, and paired t tests were used to determine whether a significant change occurred. Spearman's rank correlation was also used to compare CBF with glucose metabolism in the same region. RESULTS:The analysis primarily revealed that after bypass surgery, a statistically significant increase occurred in the CBF on the affected side (P < 0.01). The postprocedural SUVR was not significantly higher than the preprocedural SUVR (P > 0.05). However, the postprocedural AI values for CBF and SUVR were significantly lower after surgery than before surgery (P < 0.01). A significant correlation was found between the AI values for preoperative CBF and SUVR on the ipsilateral hemisphere (P < 0.01). CONCLUSIONS:The present study demonstrates that a combination of ASL and 18F-FDG PET could be used to simultaneously analyse changes in patients' cerebral haemodynamic patterns and metabolism between before and after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery. This therefore represents an essential tool for the evaluation of critical haemodynamic and metabolic status in patients with symptomatic unilateral ischaemic cerebrovascular disease.
Project description:Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo-continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received (15)O-water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross-modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = -0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional (15)O-water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non-invasive in vivo examination of early pathophysiological changes in AD.
Project description:Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic-ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous (15)O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq (15)O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and -0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq (15)O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion.
Project description:Brain and tumour blood flow can be measured noninvasively using arterial spin labelling (ASL) magnetic resonance imaging (MRI), but reliable quantification in mouse models remains difficult. Pseudocontinuous ASL (pCASL) is recommended as the clinical standard for ASL and can be improved using multiphase labelling (MP pCASL). The aim of this study was to optimise and validate MP pCASL MRI for cerebral blood flow (CBF) measurement in mice and to assess its sensitivity to tumour perfusion. Following optimization of the MP pCASL sequence, CBF data were compared with gold-standard autoradiography, showing close agreement. Subsequently, MP pCASL data were acquired at weekly intervals in models of primary and secondary brain tumours, and tumour microvessel density was determined histologically. MP pCASL measurements in a secondary brain tumour model revealed a significant reduction in blood flow at day 35 after induction, despite a higher density of blood vessels. Tumour core regions also showed reduced blood flow compared with the tumour rim. Similarly, significant reductions in CBF were found in a model of glioma 28 days after tumour induction, together with an increased density of blood vessels. These findings indicate that MP pCASL MRI provides accurate and robust measurements of cerebral blood flow in naïve mice and is sensitive to changes in tumour perfusion.