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Objective This study aimed to quantify chronological cerebral blood flow (CBF) changes using arterial spin labeling (ASL) magnetic resonance imaging in patients with reversible cerebral vasoconstriction syndrome (RCVS). Background Quantitative ASL analyses in RCVS have not been well described in the literature. Methods Quantification of ASL using an automated region-of-interest placement software and a 5-point visual scale of vasoconstriction severity was performed in five RCVS patients. The association between CBF changes and RCVS-related complications was evaluated. Results Quantitative ASL revealed variable patterns of decreasing CBF in the first week, followed by subsequent increases. Notably, arterial vasoconstriction paradoxically progressed despite an increase in CBF from the first to the second week; this increase was relatively higher in patients with both cortical subarachnoid hemorrhage and posterior reversible encephalopathy syndrome. Conclusions Quantitative ASL revealed that CBF initially decreased and subsequently increased, especially in the second week. These changes may serve as surrogate imaging markers for RCVS-related complications, and could further contribute to understanding the pathology of RCVS.

Background Arterial transit time correction by data acquisition with multiple post-labeling delays (PLDs) or relatively long PLDs is expected to obtain more accurate imaging in cases of the cerebrovascular steno-occlusive disease. However, there have so far been no reports describing the significance of arterial spin labeling (ASL) images at short PLDs regarding the evaluation of cerebral circulation in ischemic cerebrovascular disease. Purpose To clarify the role of short-PLD ASL in cerebrovascular steno-occlusive disease. Material and Methods Fifty-three patients with cerebrovascular steno-occlusive disease were included in this study. All patients underwent ASL magnetic resonance imaging and 15O-PET within two days of each modality. To compare the ASL findings with each parameter of PET, the right-to-left (R/L) ratio, defined as the right middle cerebral artery (MCA) value/left MCA value, was calculated. Results There is a significant correlation between the ASL images at a short PLD and the ratio of cerebral blood flow and cerebral blood volume by 15O-PET, which may accurately reflect the cerebral perfusion pressure. A receiver operating characteristic curve analysis indicated that ASL images at PLD 1000 and 1500 ms were more accurate than at PLD 2000–3000 ms for the detection of a ≥10% change in the PET cerebral blood flow. Conclusion ASL images at shorter PLDs may be useful at least as a screening modality to detect the changes in the cerebral circulation in cerebrovascular steno-occlusive disease. We must evaluate ASL images at multiple PLDs while considering the arterial transit time of each case at present.

It is unclear whether the visual assessment of noninvasive arterial spin labeling magnetic resonance imaging (ASL) can identify instances of hemodynamic compromise including an elevated oxygen extraction fraction (OEF) measured by 15O-gas positron emission tomography (PET). Here we evaluated the relationship between a four-point visual assessment system referred to as 'ASL scores' using ASL with two postlabeling delays (PLDs; 1525 ms and 2525 ms) and some quantitative hemodynamic parameters measured by PET. We retrospectively evaluated the cases of 18 Japanese patients with moyamoya disease who underwent ASL and PET. We compared the patients' regional ASL scores on two ASL images to the regional values of PET parameters, and we observed a significant trend in accord with the presumed clinical severity among all PET parameters and ASL scores (p

Background Contrast-induced encephalopathy (CIE) is a rare and misdiagnosed complication of intravascular injection of contrast, responsible for arterial vasospasm and neurologic effects. Conventional radiologic findings are not in themselves specific for cerebral vasospasm diagnosis. We present a case in which arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) was useful in early diagnosis of CIE. Case Description A 56-year-old woman was admitted for elective flow-diverter embolization of a recanalized left supra-ophthalmic internal carotid artery aneurysm; at 4 hours postprocedure, she acutely developed sensitive aphasia and right arm paresis. Although no-contrast computed tomography and MRI with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences did not demonstrate acute ischemic/hemorrhagic cerebral foci or cortical edema, ASL showed decreased cerebral blood flow (CBF) in the insular-temporal-parietal anterior lobe, suspected for hypoperfusion due to vasospasm, which was not confirmed by subsequent emergent digital subtraction angiography. At 16 hours, because of worsening symptoms, patient underwent an additional MRI, which showed slight insular cortical edema on fluid-attenuated inversion recovery and corresponding slight restricted diffusion-weighted imaging with a severe reduction in CBF value; at this time, emergent digital subtraction angiography demonstrated distal arterial vasospasm of left middle cerebral artery, and vasospasm therapy was started. Within 48 hours of symptom onset, the patient gradually improved to a complete neurologic recovery, with normalization of CBF values in the concerning cerebral region. Conclusions CIE should always be considered in patients with focal neurologic deficits after iodinate contrast exposure. ASL perfusion MRI with CBF maps could be a promising tool for prompt, early confirmation of underlying vasospasm, as cortical edema and distal vasospasm could not be detected on conventional radiologic imaging.

Prolonged mastication may induce an asymmetric modification of the local perfusion of the trigeminal principal nucleus. The aim of the present study was to evaluate the possible influence of vitamin C (vit. C) on such effect. Four groups of healthy volunteers underwent arterial spin labeling magnetic resonance imaging (ASL-MRI) to evaluate the local perfusion of the trigeminal nuclei after a vit. C-enriched lunch or a control lunch. Two ASL-MRI scans were acquired, respectively, before and after a 1 h-long masticating exercise or a 1 h long resting period. The results showed (i) an increased global perfusion of the brain in the vit. C-enriched lunch groups, (ii) an increased local perfusion of the right principal trigeminal nucleus (Vp) due to mastication, and (iii) a reduction of the rightward asymmetry of the Vp perfusion, due to mastication, after the vit C-enriched meal compared to the control meal. These results confirmed a long-lasting effect of prolonged mastication on Vp perfusion and also suggest a possible effect of vit. C on cerebral vascular tone regulation. Moreover, the data strongly draw attention on the side-to-side relation in Vp perfusion as a possible physiological parameter to be considered to understand the origin of pathological conditions like migraine.

Background Differentiating sellar region meningiomas from pituitary adenomas on standard magnetic resonance imaging (MRI) sequences can be difficult. Arterial spin labeling (ASL) is a noninvasive technique of magnetic resonance perfusion imaging. The range of applications of ASL in neurosurgery has increased, and the information provided can be unique and complementary to other MRI sequences. Here we investigate the utility of ASL MRI in differentiating between sellar region meningiomas and pituitary adenomas. Methods This was a retrospective comparison of quantitative assessments on absolute and normalized tumor blood flow in histologically proven meningiomas versus pituitary adenomas. Results A total of 15 patients with sellar region lesions were identified, including 9 meningiomas and 6 pituitary adenomas. Mean absolute tumor blood flow and normalized tumor blood flow were significantly higher in meningiomas (131 mL/100 g/min and 2.22) than adenomas (47 mL/100 g/min and 0.92; P Conclusions ASL MRI is a useful adjunct sequence in differentiating sellar region meningiomas, which exhibit high perfusion, from pituitary adenomas, which exhibit relatively low perfusion.

Background and Objectives: Determining the occlusion site and collateral blood flow is important in acute ischemic stroke. The purpose of the current study was to test whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) could be used to identify the occlusion site and collateral perfusion, using digital subtraction angiography (DSA) as a gold standard. Method: Data from 521 consecutive patients who presented with acute ischemic stroke at our institution from January 2012 to September 2014 were retrospectively reviewed. Image data were included in this study if: (1) the patient presented symptoms of acute ischemic stroke; (2) MRI was performed within 24 h of symptom onset; and (3) DSA following MRI was performed (n = 32 patients). We defined proximal intra-arterial sign (IAS) on ASL as enlarged circular or linear bright hyperintense signal within the occluded artery and distal IAS as enlarged circular or linear bright hyperintense signals within arteries inside or surrounding the affected region. The presence or absence of the proximal IAS and distal IAS were assessed, along with their inter-rater agreement and consistency with the presence of occlusion site and collateral flow on DSA images. Results: The sensitivity and specificity for identifying occlusion site with ASL were 82.8 and 100%, respectively. Those for identifying collateral flow with ASL were 96.7 and 50%, respectively. The inter-rater reliability was excellent for proximal IAS (κ = 0.92; 95% CI 0.76–1.00) and substantial for distal IAS detection (κ = 0.78; 95% CI 0.38–1.00). Conclusions: Proximal IAS and distal IAS on ASL imaging can provide important diagnostic clues for the detection of arterial occlusion sites and collateral perfusion in patients with acute ischemic stroke.

Arterial spin labeling is a noninvasive, non-gadolinium-dependent magnetic resonance imaging (MRI) technique to assess cerebral blood flow. It provides insight into both tissue metabolic activity and vascular supply. Because of its non-sensitivity toward blood–brain barrier leakage, arterial spin labeling is also more accurate in cerebral blood flow quantification than gadolinium-dependent methods. The aim of this pictorial essay is to promote the application of arterial spin labeling in pediatric neuroradiology. The authors provide information on artifacts and pitfalls as well as numerous fields of application based on pediatric cases.

Case Non-convulsive status epilepticus (NCSE) is among the differential diagnoses of decreased consciousness, but often presents a diagnostic challenge. A 65-year-old woman was admitted to our emergency department with bradylalia. No abnormal finding was detected by computed tomography or magnetic resonance imaging. Subsequently, acquired arterial spin-labeling images showed hyperperfusion in the right hemisphere. Outcome After the examination, the patient began experiencing left hemifacial seizures, which were relieved by diazepam; however, she was still agitated. Ictal confusion due to NCSE was suspected. Electroencephalography revealed periodic, generalized epileptiform activities with brief seizures of facial muscles by intermittent photic stimulation. Another supportive case of NCSE detected by arterial spin-labeling from a 56-year-old right-handed man has also been presented. Conclusion Arterial spin-labeling magnetic resonance perfusion imaging provides valuable information regarding cerebral perfusion status in NCSE patients in emergency/acute settings.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can assess cerebral blood flow (CBF) without using radiolabeled tracers. It is unknown whether regional increases in CBF on ASL MRI correlate with seizure location in newborns. We report 3 newborns with focal seizures localized on continuous video electroencephalogram (cEEG), anatomical brain MRI, and ASL MRI. Each patient underwent pseudocontinuous ASL with segmented 3-dimensional fast spin echo readout as part of standard care. Case 1 is a term male infant presenting with left temporal status epilepticus and recurrent cEEG seizures from an idiopathic large left intraventricular hemorrhage. ASL images demonstrated left mesial temporal lobe increased CBF. Case 2 is a late preterm male infant presenting with recurrent cEEG seizures due to focal right megalencephaly. Ictal EEG and ASL images coincided with the focal dysplasia. Case 3 is a dysmorphic term female infant with nonconvulsive partial status epilepticus identified by focal increased CBF of the left temporal lobe on ASL images. The area of increased CBF was within an area of extensive left hemisphere dysplasia. To our knowledge, this is the first report of regional increases in CBF on ASL MRI correlating with ictal cEEG in newborns.

The hemodynamics in the brains of individuals with Moyamoya disease are complex and variable. Cerebral revascularization is an important treatment when hemodynamics are severely damaged. It’s of great value to accurately quantify blood perfusion of different functional brain regions for better postoperative prognosis. In this study, we developed methods to segment territory of middle cerebral arteries (MCA) and its functional brain regions based on T1 and arterial spin labeling (ASL) imaging, absolute and normalized cerebral blood perfusion (CBF) were calculated for target regions-of-interest (ROI), spatial coefficient of variation was introduced to detect information of arterial transit time (ATT) contained in CBF images. After revascularization of Moyamoya disease, we detected perfusion improvement within MCA territory, while different alterations exist within different functional sub-regions. We also conformed that the spatial coefficient of variation of ASL CBF images can be used as an alternative ROI-based hemodynamic measurement to predict alterations of ATT. In summary, our methods show potential in postoperative evaluation of patients with Moyamoya disease.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is an imaging methodology that uses blood as an endogenous contrast agent to quantify flow. One limitation of this method of capillary blood quantification when applied in the lung is the contribution of signals from non-capillary blood. Intensity thresholding is one approach that has been proposed for minimizing the non-capillary blood signal. This method has been tested in previous in silico modeling studies; however, it has only been tested under a restricted set of physiological conditions (supine posture and a cardiac output of 5L/min). This study presents an in silico approach that extends previous intensity thresholding analysis to estimate the optimal "per-slice" intensity threshold value using the individual components of the simulated ASL signal (signal arising independently from capillary blood as well as pulmonary arterial and pulmonary venous blood). The aim of this study was to assess whether the threshold value should vary with slice location, posture, or cardiac output. We applied an in silico modeling approach to predict the blood flow distribution and the corresponding ASL quantification of pulmonary perfusion in multiple sagittal imaging slices. There was a significant increase in ASL signal and heterogeneity (COV=0.90 to COV=1.65) of ASL signals when slice location changed from lateral to medial. Heterogeneity of the ASL signal within a slice was significantly lower (P=0.03) in prone (COV=1.08) compared to in the supine posture (COV=1.17). Increasing stroke volume resulted in an increase in ASL signal and conversely an increase in heart rate resulted in a decrease in ASL signal. However, when cardiac output was increased via an increase in both stroke volume and heart rate, ASL signal remained relatively constant. Despite these differences, we conclude that a threshold value of 35% provides optimal removal of large vessel signal independent of slice location, posture, and cardiac output.

Key Points Question Is midlife cardiovascular risk associated with cerebral blood flow in older age, and does this association vary with age? Findings In this longitudinal cohort study of 116 older adults without dementia, higher cardiovascular risk scores during a 20-year period were significantly associated with lower cerebral blood flow to the medial temporal, parietal, and occipital cortices. The association varied during the life span such that cardiovascular risk in midlife but not in later life was significantly associated with cerebral hypoperfusion in older age. Meaning Because cerebral hypoperfusion is an early mechanism in Alzheimer disease and vascular dementia, these findings may inform the development of dementia prevention strategies aimed at managing cardiovascular health., This longitudinal cohort study examines the association of midlife cardiovascular risk factors with cerebral perfusion at older ages among adults without dementia., Importance Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults. Objective To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages. Design, Setting, and Participants In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018. Exposures Framingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits. Main Outcomes and Measures Cerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging. Results Of 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072; P

Purpose To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. Materials and Methods PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland–Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m2. Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland–Altman plot for cortical RBF showed good agreement between the two measurements. Conclusion PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. Level of Evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813–819

Background and Purpose— Arterial spin-labeling magnetic resonance imaging is sensitive for detecting hyperemic lesions (HLs) in patients with acute ischemic stroke. We evaluated whether HLs could predict blood–brain barrier (BBB) disruption and hemorrhagic transformation (HT) in acute ischemic stroke patients. Methods— In a retrospective study, arterial spin-labeling was performed within 6 hours of symptom onset before revascularization treatment in 25 patients with anterior circulation large vessel occlusion on baseline magnetic resonance angiography. All patients underwent angiographic procedures intended for endovascular therapy and a noncontrast computed tomography scan immediately after treatment. BBB disruption was defined as a hyperdense lesion present on the posttreatment computed tomography scan. A subacute magnetic resonance imaging or computed tomography scan was performed during the subacute phase to assess HTs. The relationship between HLs and BBB disruption and HT was examined using the Alberta Stroke Program Early Computed Tomography Score locations in the symptomatic hemispheres. Results— A HL was defined as a region where CBF relative ≥1.4 (CBF relative =CBF HL /CBF contralateral ). HLs, BBB disruption, and HT were found in 9, 15, and 15 patients, respectively. Compared with the patients without HLs, the patients with HLs had a higher incidence of both BBB disruption (100% versus 37.5%; P =0.003) and HT (100% versus 37.5%; P =0.003). Based on the Alberta Stroke Program Early Computed Tomography Score locations, 21 regions of interests displayed HLs. Compared with the regions of interests without HLs, the regions of interests with HLs had a higher incidence of both BBB disruption (42.8% versus 3.9%; P P Conclusions— HLs detected on pretreatment arterial spin-labeling maps may enable the prediction and localization of subsequent BBB disruption and HT.

Arterial spin labeling (ASL) MRI allows the quantification of tissue perfusion without administration of exogenous contrast agents. Patients with reduced renal function or other contraindications to Gadolinium-based contrast media may benefit from the non-invasive monitoring of tissue microcirculation. So far, only few studies have investigated the sensitivity, the specificity and the reliability of the ASL techniques for the assessment of renal perfusion. Moreover, only little is known about the interplay between ASL markers of perfusion and functional renal filtration parameters. In this editorial, we discuss the main technical issues related to the quantification of renal perfusion by ASL and, in particular, the latest results in patients with kidney disorders.

Objective To investigate the age-dependent changes in regional cerebral blood flow (CBF) in healthy adults by fitting mathematical models to imaging data. Materials and Methods In this prospective study, 90 healthy adults underwent pseudo-continuous arterial spin labeling imaging of the brain. Regional CBF values were extracted from the arterial spin labeling images of each subject. Multivariable regression with the Akaike information criterion, link test, and F test (Ramsey's regression equation specification error test) was performed for 7 models in every brain region to determine the best mathematical model for fitting the relationship between CBF and age. Results Of all 87 brain regions, 68 brain regions were best fitted by cubic models, 9 brain regions were best fitted by quadratic models, and 10 brain regions were best fitted by linear models. In most brain regions (global gray matter and the other 65 brain regions), CBF decreased nonlinearly with aging, and the rate of CBF reduction decreased with aging, gradually approaching 0 after approximately 60. CBF in some regions of the frontal, parietal, and occipital lobes increased nonlinearly with aging before age 30, approximately, and decreased nonlinearly with aging for the rest of life. Conclusion In adults, the age-related perfusion patterns in most brain regions were best fitted by the cubic models, and age-dependent CBF changes were nonlinear.

Background Differential diagnosis between acute ischemic stroke (AIS) and epilepsy-related stroke mimics is sometimes difficult in the emergency department. We investigated whether a combination of diffusion-weighted imaging (DWI) and arterial spin labeling imaging (ASL) is useful in distinguishing AIS from epileptic disorders. Methods The study included suspected AIS patients who underwent emergency MRI including both DWI and ASL, and who exhibited DWI high-intensity lesions corresponding to neurological symptoms. We investigated the relationship between the ASL results from within and/or around DWI lesions and the final clinical diagnosis. Results Eighty-five cases were included (mean age, 71 ± 13 years; 47 men). The time from onset to the MRI examination was 493 ± 536 minutes. ASL showed hyperintensity in 13 patients, isointensity in 43, and hypointensity in 29. All ASL hyperintensities were observed in the cortex, with 4 patients (31%) presenting with AIS and 9 (69%) with an epileptic disorder. All of the AIS patients with ASL hyperintensity were diagnosed with cardioembolic stroke (4/4, 100%), with magnetic resonance angiography demonstrating recanalization of the occluded artery in all cases (4/4, 100%). In the 9 patients with an epileptic disorder, the area of ASL hyperintensity typically extended beyond the vascular territory (7/9, 78%) and involved the ipsilateral thalamus (7/9, 78%). All patients with ASL isointensity and hypointensity were diagnosed with AIS; none had epileptic disorders. Conclusions Although cortical ASL hyperintensity can indicate cardioembolic stroke with recanalization, hyperintensity beyond the vascular territory may alternatively suggest an epileptic disorder in suspected AIS patients with DWI lesions.

Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (Kw) across the blood–brain barrier in humans. This study aimed to evaluate the blood–brain barrier disruption in transient (60 min) ischemic stroke using Kw magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group Kw magnetic resonance imaging data showed no significant blood–brain barrier permeability changes, although a few animals showed slightly abnormal Kw. Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, Kw magnetic resonance imaging revealed significant blood–brain barrier disruption. Regions with abnormal Kw showed substantial overlap with regions of hyperintense T2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The Kw values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min−1, respectively (P w magnetic resonance imaging is sensitive to blood–brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. Kw magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

Background and purpose Locating the epileptogenic zone (EZ) in patients with neocortical epilepsy presents major challenges. Our aim was to assess the accuracy of arterial spin labeling (ASL), an emerging non-invasive magnetic resonance imaging (MRI) perfusion technique, to locate the EZ in patients with drug-resistant neocortical epilepsy. Methods Twenty-five consecutive patients with neocortical epilepsy referred to our epilepsy unit for pre-surgical evaluation underwent a standardized assessment including video-electroencephalography (EEG) monitoring, structural MRI, subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) and fluorodeoxyglucose positron emission tomography (FDG-PET) studies. An ASL sequence was included in the MRI studies. Areas of hypoperfusion or hyperperfusion on ASL were classified into 15 anatomic-functional cortical regions; these regional cerebral blood flow maps were compared with the EZ determined by the other tests and the strength of concordance was assessed with the kappa coefficient. Results Of the 25 patients [16 (64%) women; mean age 32.4 (±13.8) years], 18 (72%) had lesions on structural MRI. ASL abnormalities were seen in 15 (60%) patients (nine hypoperfusion, six hyperperfusion). ASL had a very good concordance with FDG-PET (k = 0.84), a good concordance with structural MRI (k = 0.76), a moderate concordance with video-EEG monitoring (k = 0.53) and a fair concordance with SISCOM (k = 0.28). Conclusion Arterial spin labeling might help to confirm the location and extent of the EZ in the pre-surgical workup of patients with drug-resistant neocortical epilepsy.

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 simultaneous15O-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 MBq15O-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 MBq15O-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.

OBJECT Arterial spin labeling (ASL)-MRI is becoming a routinely used sequence for ischemic strokes, as it quantifies cerebral blood flow (CBF) without the need for contrast injection. As brain arteriovenous malformations (AVMs) are highflow vascular abnormalities, increased CBF can be identified inside the nidus or draining veins. The authors aimed to analyze the relevance of ASL-MRI in the diagnosis and follow-up of children with brain AVM. METHODS The authors performed a retrospective analysis of 21 patients who had undergone digital subtraction angiography (DSA) and pseudo-continuous ASL-MRI for the diagnosis or follow-up of brain AVM after radiosurgery or embolization. They compared the AVM nidus location between ASL-MRI and 3D contrast-enhanced T1 MRI, as well as the CBF values obtained in the nidus (CBFnidus) and the normal cortex (CBFcortex) before and after treatment. RESULTS The ASL-MRI correctly demonstrated the nidus location in all cases. Nidal perfusion (mean CBFnidus 137.7 ml/100 mg/min) was significantly higher than perfusion in the contralateral normal cortex (mean CBFcortex 58.6 ml/100 mg/min; p < 0.0001, Mann-Whitney test). Among 3 patients followed up after embolization, a reduction in both AVM size and CBF values was noted. Among 5 patients followed up after radiosurgery, a reduction in the nidus size was observed, whereas CBFnidus remained higher than CBFcortex. CONCLUSIONS In this study, ASL-MRI revealed nidus location and patency after treatment thanks to its ability to demonstrate focal increased CBF values. Absolute quantification of CBF values could be relevant in the follow-up of pediatric brain AVM after partial treatment, although this must be confirmed in larger prospective trials.

Introduction: Dynamic susceptibility contrast (DSC) perfusion and pulsed arterial spin labeling (PASL) imaging are newer advanced magnetic resonance sequences which are capable of detecting vascular changes in patients with new-onset seizure disorder even when no significant abnormalities are visualized on conventional sequences. The purpose of our study is to establish utility of arterial spin labeling (ASL) in new-onset seizure patients and compare ASL with DSC perfusion sequence. Materials and Methods: Twenty-six patients coming to emergency department with new-onset seizure disorder were evaluated using DSC and ASL sequence. Perfusion asymmetry was assessed using region of interests taken at places where signal asymmetry was maximal. Results: PASL sequence showed focal vascular changes in form of hyperperfusion in four patients, hypoperfusion in nine patients, and normal perfusion in 13 patients. Altered perfusion whether hypo/hyperperfusion was detected in five out of 16 patients even when conventional sequences were normal. There was strong positive linear correlation between ASL and DSC with P = 0.001. Conclusion: Noninvasive PASL is capable of detecting vascular changes induced by seizure and is comparable to DSC sequence. Thus, it is recommended when there is a need for repeated evaluations; in follow-up/therapy response assessment and when contrast administration is contraindicated.

Background: The susceptibility vessel sign on gradient echo-type-T2*-weighted imaging is a well-known marker of arterial occlusion. Stagnant flow in front of the middle cerebral artery (MCA) occlusion sites may contribute to the intra-arterial, high-intensity signal on arterial spin labeling magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared the intra-arterial, high-intensity signal and susceptibility vessel sign in patients with symptomatic MCA occlusion and patients without major vessel occlusion. Methods: We identified transient ischemic attack or ischemic stroke patients with (1) 3-T MRI performed within 24 h after clinical onset including arterial spin labeling, T2*-weighted imaging, and magnetic resonance angiography (MRA) and (2) either having MCA occlusion (n = 34 patients) or without major vessel occlusion (n = 24 patients). The intra-arterial, high-intensity signal was defined as an enlarged circular or linear bright hyperintensity within the artery. The susceptibility vessel sign was defined as an enlarged spot of hypointensity within the MCA, in which the diameter of the hypointense signal within the vessel exceeded the contralateral vessel diameter. The presence or absence of the intra-arterial, high-intensity signal and susceptibility vessel sign were assessed, along with their inter-rater agreement and consistency with the presence of MCA occlusion on MRA. Results: The intra-arterial, high-intensity signal was detectable in 30 patients (52%), and susceptibility vessel sign was observed in 17 patients (29%). The sensitivity of the intra-arterial high-intensity signal was significantly higher than that of the susceptibility vessel sign (88% vs. 50%; p < 0.05). The accuracy of the intra-arterial high-intensity signal was also higher than that of the susceptibility vessel sign (93% vs. 71%; p < 0.05). The intra-arterial high-intensity signal was situated in the proximal regions of the susceptibility vessel sign on T2*WI within the MCA. Neither the intra-arterial high-intensity signal nor the susceptibility vessel sign was observed in patients without major vessel occlusion. Inter-rater agreement was good for intra-arterial high-intensity signal detection (κ = 0.73) and moderate for susceptibility vessel sign detection (κ = 0.47). The presence or absence of the intra-arterial high-intensity signal was highly consistent with that of MCA occlusion on MRA (κ = 0.74). Conclusions: The intra-arterial high-intensity signal on arterial spin labeling appears to be useful to identify the presence of acute MCA occlusion and may be associated with stagnant flow in front of occlusion sites. The intra-arterial high-intensity signal may also be used to identify the occlusion site.

Arterial spin labeling (ASL) magnetic resonance (MR) imaging enables evaluation of perfusion. Because of its noninvasiveness, this technique is particularly useful in vulnerable patient populations such as infants or patients with kidney disease. This article describes the commonly used ASL techniques and gives an overview of clinical applications. Furthermore, it introduces the reader to recent advances in ASL MR imaging that enable full hemodynamic assessment.

Purpose Quantitative measure of blood flow provides important information regarding renal function, nephropathies and viability of kidney transplantation. Therefore, a method that would allow quantitative and reliable assessment of the renal microvascular perfusion would be very valuable. Arterial spin labeling Magnetic Resonance Imaging has started to be widely used for human studies. For rodents though, despite the increasing number of transgenic mouse models, renal perfusion Magnetic Resonance Imaging has been only sparsely reported. This study investigated the use of FAIR (flow-sensitive alternating inversion recovery) and pseudo-continuous arterial spin labeling (pCASL) for mouse renal blood flow measurements. Methods FAIR and pCASL were compared in terms of sensitivity, absolute quantification, reproducibility and flexibility of implementation. Multislice and coronal imaging were also investigated. Studies were performed at 11.75 T with volumic transmitter/receiver radiofrequency coils and fast imaging. Results pCASL demonstrated better experimental flexibility and higher sensitivity compared to FAIR (> +20%). Renal blood flow values in the range of 550–750 mL/100 g/min for the cortex and of 140–230 mL/100 g/min for the medulla, consistent with literature data, were measured. Conclusion pCASL was successfully applied at very high field for mouse renal blood flow measurements, demonstrating high sensitivity, flexibility and multislice imaging capability. pCASL may be considered as a method of choice for mouse kidney perfusion studies. Magn Reson Med 71:1186–1196, 2014. © 2013 Wiley Periodicals, Inc.

Cerebral perfusion monitoring is an important component of hyperacute stroke treatment. Arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging provides a noninvasive method of cerebral perfusion observation. Rapid changes in cerebral perfusion were demonstrated in two patients admitted one hour after onset of hyperacute stroke who underwent recombinant tissue plasminogen activator (rt-PA) treatment. Serial MR images and ASL images were taken on admission and after rt-PA administration. Cerebral blood flow (CBF) values were obtained using the CBF workstation and analysis software. Interpretable ASL images were taken in both patients. Perfusion deficits were consistent with symptoms and/or MR angiography imaging abnormalities. Delayed arterial transit effect was present in one patient; serial imaging showed improvement of CBF after rt-PA treatment in both patients. ASL perfusion MR imaging can provide rapid noninvasive multislice imaging in hyperacute ischemic stroke, and can depict early perfusion deficit and quantify regional CBF concomitantly., Article, NEUROLOGIA MEDICO-CHIRURGICA. 53(4):213-216 (2013)

Background The congestion of spin-labeled blood at large-vessel occlusion can present as hyperintense signals on perfusion magnetic resonance imaging with 3-dimensional pseudo-continuous arterial spin labeling (proximal bright vessel sign). The purpose of this study was to clarify the difference between proximal bright vessel sign and susceptibility vessel sign in acute cardioembolic cerebral infarction. Methods Forty-two patients with cardioembolic cerebral infarction in the anterior circulation territory underwent magnetic resonance imaging including diffusion-weighted imaging, 3-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging, T2*-weighted imaging, and 3-dimensional time-of-flight magnetic resonance angiography using a 3-T magnetic resonance scanner. Visual assessments of proximal bright vessel sign and the susceptibility vessel sign were performed by consensus of 2 experienced neuroradiologists. The relationship between these signs and the occlusion site of magnetic resonance angiography was also investigated. Results Among 42 patients with cardioembolic cerebral infarction, 24 patients showed proximal bright vessel sign (57.1%) and 25 showed susceptibility vessel sign (59.5%). There were 19 cases of proximal bright vessel sign and susceptibility vessel sign-clear, 12 cases of proximal bright vessel sign and susceptibility vessel sign-unclear, and 11 mismatched cases. Four out of 6 patients with proximal bright vessel sign-unclear and susceptibility vessel sign-clear showed distal middle cerebral artery occlusion, and 2 out of 5 patients with proximal bright vessel sign-clear and susceptibility vessel sign-unclear showed no occlusion on magnetic resonance angiography. Conclusions Proximal bright vessel sign is almost compatible with susceptibility vessel sign in patients with cardioembolic cerebral infarction.

The magnetic resonance imaging technique known as territorial arterial spin labeling (TASL) allows for noninvasive visualization of perfusion territories. The objective of this study was to use TASL to assess the relationship between perioperative changes in the perfusion territories of the internal carotid artery (ICA) and cerebral blood flow (CBF) after carotid revascularization.In 32 patients, ICA perfusion volume (PV) and CBF were measured before and after carotid endarterectomy/carotid artery stenting using TASL and single-photon emission computed tomography, respectively. ICA flow was measured during carotid endarterectomy before and after reconstruction, using an electromagnetic flowmeter. Eleven healthy volunteers, as the normal control group, underwent TASL evaluation.We classified patients into 2 groups: the normal PV group (ICA PV ≥ mean-2 standard deviation of healthy volunteers; n = 13) and the reduced PV group (ICA PVmean-2 standard deviation; n = 19). The postoperative increase in the ICA PV and CBF were significantly greater in the reduced PV group than in the normal group (90.4% ± 131.8% vs. 10.5 ± 9.8%, P = 0.017, 32.0 ± 25.7% vs. 10.5% ± 10.7%, P = 0.0032, respectively). ICA flow increased significantly after reconstruction in both the normal PV group (115.1 ± 48.1 mL/minute to 159.1 ± 53 mL/minute; P = 0.016) and reduced PV group (57.8 ± 38.3 mL/minute to 182.3 ± 52.6 mL/minute; P 0.0001). However, in some patients in the reduced PV group, the PV increased only slightly, whereas the ICA flow markedly increased, which resulted in a large CBF increase, such as hyperperfusion.The TASL study suggested that an imbalance between increases in the PV and ICA flow could play an important role in the pathophysiology underlying postoperative abnormal increases in CBF.

Until recently, no direct comparison between [15O]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 [15O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [15O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant ( P15O]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.

Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [15O]-water radiotracer. Although [15O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [15O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.

Background and Purpose— Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively. Methods— ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades. Results— The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52–0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77–0.88) and 0.82 (95% confidence interval, 0.76–0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade ( P Conclusions— ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted.

Our objectives were to compare the effects of subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD) on cerebral blood flow (CBF), and then to analyze the relationship between CBF and subcortical vascular disease, measured as volume of white-matter lesions (WMLs).Eight mildly demented patients with SIVD (mean +/- SD; aged 77 +/- 8 years; Mini-Mental State Examination score 26 +/- 3 years) and 14 patients with AD were compared with 18 cognitively normal elderly subjects. All subjects had CBF measured using arterial spin-labeling magnetic resonance imaging, and brain volumes were assessed using structural magnetic resonance imaging.AD and SIVD showed marked CBF reductions in the frontal (P = 0.001) and parietal (P = 0.001) cortices. In SIVD, increased subcortical WMLs were associated with reduced CBF in the frontal cortex (P = 0.04), in addition to cortical atrophy (frontal, P = 0.05; parietal, P = 0.03).Subcortical vascular disease is associated with reduced CBF in the cortex, irrespective of brain atrophy.

Background Cerebral ischemia plays a major role in pathophysiology of the injured brain. Most of the currently available methods of cerebral blood flow (CBF) monitors are either indirect measure of CBF or needing radioactive agents for data acquisition. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a noninvasive method of measuring CBF. The aim of our study was to determine the differences in the CBF values between propofol and sevoflurane anesthesia using ASL-MRI technique in mechanically ventilated patients with cerebrovascular disease. Methods After ethics board approval and informed consent, we measured CBF in 4 patients with moyamoya disease, using a pseudo-continuous 3D ASL sequence available on a 3.0 T MRI scanner. Patients were anesthetized first with sevoflurane (1 MAC) and then anesthesia was converted to total intravenous anesthesia with propofol (100 to 125 μg/kg/min). When the patient was in a steady state with respect to anesthesia and normocapnia (baseline PETCO2), CBF was measured under both sevoflurane and propofol anesthesia. Results Quantitative estimation of both global and regional CBF was successfully performed in all patients. The mean global CBF in gray and white matter of all patients under propofol anesthesia were 38.4 and 31.6 mL/100 g/min, respectively. Similar values under sevoflurane anesthesia were 56.6 mL/100 g/min for gray matter and 42.5 mL/100 g/min for white matter. Conclusions ASL-MRI is a feasible, noninvasive method of quantitative estimation of global and regional CBF in mechanically ventilated patients under anesthesia. In this pilot study CBF was consistently greater with sevoflurane than with propofol.

Background: Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. Objective: We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. Methods: The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. Results: While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. Conclusion: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum.

Functional magnetic resonance imaging (fMRI) has become a premiere technique for studying the development and neural mediation of a wide range of typical and atypical behaviors in children. While the mechanism of the blood oxygen level-dependent (BOLD) fMRI signal has been a focus of investigation in the mature brain, it has been largely unexamined in the developing brain. One critical component of the BOLD signal that has been noted to change with age is cerebral blood flow (CBF). Reports of CBF in children based on clinical radioactive tracing methods have found elevated CBF in childhood relative to adulthood, which could affect the BOLD response. This study used non-invasive arterial spin labeling magnetic resonance imaging to study resting state and activity-driven CBF in conjunction with the functional BOLD response in healthy children 8 and 12 years of age and in adults. Participants performed a finger-tapping task to generate robust activation measured in the motor cortex. Quantification of resting state CBF demonstrated higher CBF in 8 year olds and in 12 year olds relative to adults. The absolute increase in CBF between baseline rest and peak response during the motor task was also higher in both child groups compared to adults. In contrast, the relative increase of CBF above baseline, expressed as percent of CBF change, was comparable across groups. The percent of BOLD signal change was also stable across age groups. This set of findings suggests that along with elevated CBF in childhood, other component processes of the BOLD response are also in an elevated state such that together they yield a net BOLD effect that resembles adults. These findings coincide with our previous examination of hemodynamics in primary sensory cortex. Although the magnitude of the BOLD response appears consistent between childhood and adulthood, the underlying physiology and cerebrovascular dynamics that give rise to the BOLD effect differ between immature and mature neural systems.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times. Magn Reson Med 41:829–840, 1999. © 1999 Wiley-Liss, Inc.

Background and purpose Arterial spin labeling (ASL) is a non-invasive modality of magnetic resonance imaging (MRI) used to evaluate cerebral perfusion without a contrast agent. The usefulness of ASL for diagnosis in the acute phase of late seizure after stroke was evaluated. Methods Twelve consecutive patients diagnosed with late seizure after stroke were enrolled in this study. MRI including ASL was performed for each patient at the time of the emergency department visit. Eight of the patients underwent electroencephalography (EEG). Results All patients showed hyperperfusion around the stroke lesion on ASL. Only 6 patients showed high signal intensity along the cerebral cortex around the stroke lesion on diffusion-weighted imaging. The patients who underwent EEG showed slow activity, but paroxysmal discharges such as spikes or sharp waves were not observed. Conclusions ASL was able to reveal hyperperfusion and was of great diagnostic value in the peri-ictal phase of late seizure after stroke.

Alterations in the overall cerebral hemodynamics have been reported in multiple sclerosis (MS); however, their cause and significance is unknown. While potential venous causes have been examined, arterial causes have not. In this study, a multiple delay time arterial spin labeling magnetic resonance imaging sequence at 3T was used to quantify the arterial hemodynamic parameter bolus arrival time (BAT) and cerebral blood flow (CBF) in normal-appearing white matter (NAWM) and deep gray matter in 33 controls and 35 patients with relapsing–remitting MS. Bolus arrival time was prolonged in MS in NAWM (1.0±0.2 versus 0.9±0.2 seconds, P=0.031) and deep gray matter (0.90±0.18 versus 0.80±0.14 seconds, P=0.001) and CBF was increased in NAWM (14±4 versus 10±2 mL/100 g/min, P=0.001). Prolonged BAT in NAWM ( P=0.042) and deep gray matter ( P=0.01) were associated with higher expanded disability status score. This study demonstrates alteration in cerebral arterial hemodynamics in MS. One possible cause may be widespread inflammation. Bolus arrival time was longer in patients with greater disability independent of atrophy and T2 lesion load, suggesting alterations in cerebral arterial hemodynamics may be a marker of clinically relevant pathology.

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.

Different brain regions sense and modulate the counterregulatory responses that can occur in response to declining plasma glucose levels. The aim of this study was to determine if changes in regional cerebral blood flow (rCBF) during hypoglycemia relative to euglycemia are similar for two imaging modalities-pulsed arterial spin labeling magnetic resonance imaging (PASL-MRI) and positron emission tomography (PET). Nine healthy non-diabetic participants underwent a hyperinsulinemic euglycemic (92±3 mg/dL) - hypoglycemic (53±1 mg/dL) clamp. Counterregulatory hormone levels were collected at each of these glycemic levels and rCBF measurements within the previously described network of hypoglycemia-responsive regions (thalamus, medial prefrontal cortex and globus pallidum) were obtained using PASL-MRI and [(15)O] water PET. In response to hypoglycemia, rCBF was significantly increased in the thalamus, medial prefrontal cortex, and globus pallidum compared to euglycemia for both PASL-MRI and PET methodologies. Both imaging techniques found similar increases in rCBF in the thalamus, medial prefrontal cortex, and globus pallidum in response to hypoglycemia. These brain regions may be involved in the physiologic and symptom responses to hypoglycemia. Compared to PET, PASL-MRI may provide a less invasive, less expensive method for assessing changes in rCBF during hypoglycemia without radiation exposure.

Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9 cmH2O for 270 s) and viewed an intermittent 2 Hz flashing checkerboard, while maintaining stable end-tidal CO2. CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data., Highlights ► We examined how alterations in intrathoracic pressure affect cerebral blood flow. ► Decreased intrathoracic pressure increased global cerebral blood flow. ► The perfusion response to visual stimulation remained unaffected. ► Localized perfusion increases were observed that related to respiratory work. ► Alterations in intrathoracic pressure may confound interpretation of FMRI.

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a technique for depicting cerebral perfusion without contrast medium. The purpose of this study was to determine whether ASL can be used to detect hyperperfusion after revascularization for moyamoya disease as effectively as N-isopropyl-[123I]β-iodoamphetamine ( 123 I-IMP) single-photon emission computed tomography (SPECT). Fifteen consecutive patients with moyamoya disease were included in the study. All patients underwent surgical revascularization. Postoperatively, regional cerebral blood flow (rCBF) was measured by flow-sensitive alternating inversion recovery (FAIR) ASL and 123 I-IMP SPECT during the acute stage, and rCBF of the operative side was compared with the other side. The asymmetry ratio (AR) was then calculated from the rCBF as measured using each modality. The postoperative AR of ASL was moderately correlated with that of 123 I-IMP SPECT ( y = 0.180 x + 0.819; R = 0.80; P = .0003). In this series, 2 patients (13.3%) suffered symptomatic hyperperfusion after revascularization and accordingly exhibited increased AR of ASL. Our data indicate that early increases in rCBF in patients with hyperperfusion could be detected using FAIR ASL supplemental to 123 I-IMP SPECT after revascularization. Our data indicate that FAIR ASL is a convenient method for evaluating hyperperfusion that can be performed repeatedly without the use of contrast medium or radioisotopes.

Background The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in Alzheimer's 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. Methods We used a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched control subjects. Paired FDG-PET and ASL-MRI images from 19 control subjects and 15 AD patients were included for qualitative analysis, and paired images from 18 control subjects and 13 AD patients were suitable for quantitative analyses. Results The combined imaging protocol was well tolerated. Both modalities revealed similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD after visual review by two expert readers. Interobserver agreement was better for FDG-PET (κ: 0.75, standard error: 0.12) than ASL-MRI (κ: 0.51, standard error: 0.15); intermodality agreement was moderate to strong (κ: 0.45–0.61); and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral fluorodeoxyglucose uptake (FDG-PET) or whole-brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under receiver operating characteristic curves of 0.90 for FDG-PET (95% confidence interval: 0.79–0.99) and 0.91 for ASL-MRI (95% confidence interval: 0.80–1.00). Conclusions Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.

We investigated the time interval from labeling to peak (TLP) of perfusion-signal intensity (SIs) in normal brain using a multiphase arterial spin-labeling (ASL) magnetic resonance imaging (MRI) technique as a fundamental study to assess the temporal characteristics of perfusion SIs.Twenty temporal phases of a pulsed ASL-MRI [QUASAR, quantitative signal targeting by alternating radiofrequency pulses (STAR) labeling of arterial regions] in single-slice imaging were performed in 9 volunteers. Perfusion SIs were measured and TLPs were calculated in 14 regions of interest (ROIs), 7 in each hemisphere: thalamus, lentiform nucleus, medial frontal cortex in the anterior cerebral artery (ACA) territory, temporal cortex in the middle cerebral artery (MCA) territory, medial occipital cortex in the posterior cerebral artery (PCA) territory, anterior watershed region (AWR) and posterior watershed region (PWR).Mean TLP varied with ROI (region and mean ± standard deviation in seconds): thalamus, 1.60 ± 0.11; lentiform nucleus, 1.52 ± 0.11; ACA territory, 1.53 ± 0.16; MCA territory, 1.59 ± 0.18; PCA territory, 1.68 ± 0.20; AWR, 1.79 ± 0.14; PWR, 2.00 ± 0.20. TLP in the PWR was significantly longer than those in all other regions except the AWR, and TLP in the AWR was significantly longer than those in the lentiform nucleus and the ACA territory.Our results revealed regional differences in the temporal characteristics of perfusion SIs on ASL-MRI.

A technique has been developed for proton magnetic resonance imaging (MRI) of perfusion, using water as a freely diffusable tracer, and its application to the measurement of cerebral blood flow (CBF) in the rat is demonstrated. The method involves labeling the inflowing water proton spins in the arterial blood by inverting them continuously at the neck region and observing the effects of inversion on the intensity of brain MRI. Solution to the Bloch equations, modified to include the effects of flow, allows regional perfusion rates to be measured from an image with spin inversion, a control image, and a T1 image. Continuous spin inversion labeling the arterial blood water was accomplished, using principles of adiabatic fast passage by applying continuous-wave radiofrequency power in the presence of a magnetic field gradient in the direction of arterial flow. In the detection slice used to measure perfusion, whole brain CBF averaged 1.39 +/- 0.19 ml.g-1.min-1 (mean +/- SEM, n = 5). The technique's sensitivity to changes in CBF was measured by using graded hypercarbia, a condition that is known to increase brain perfusion. CBF vs. pCO2 data yield a best-fit straight line described by CBF (ml.g-1.min-1) = 0.052pCO2 (mm Hg) - 0.173, in excellent agreement with values in the literature. Finally, perfusion images of a freeze-injured rat brain have been obtained, demonstrating the technique's ability to detect regional abnormalities in perfusion.

Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF-BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights.

Purpose To implement a pulsed arterial spin labeling (ASL) technique in rats that accounts for cerebral blood flow (CBF) quantification errors due to arterial transit times (dt)—the time that tagged blood takes to reach the imaging slice—and outflow of the tag. Materials and Methods Wistar rats were subjected to air or 5% CO2, and flow-sensitive alternating inversion-recovery (FAIR) perfusion images were acquired. For CBF calculation, we applied the double-subtraction strategy (Buxton et al., Magn Reson Med 1998;40:383–396), in which data collected at two inversion times (TIs) are combined. Results The ASL signal fell off more rapidly than expected from TI = one second onward, due to outflow effects. Inversion times for CBF calculation were therefore chosen to be larger than the longest transit times, but short enough to avoid systematic errors caused by outflow of tagged blood. Using our method, we observed a marked regional variability in CBF and dt, and a region dependent response to hypercapnia. Conclusion Even when flow is accelerated, CBF can be accurately determined using pulsed ASL, as long as dt and outflow of the tag are accounted for. J. Magn. Reson. Imaging 2007;26:855–862. © 2007 Wiley-Liss, Inc.