A generalized signal model for dual-module velocity-selective arterial spin labeling.

PURPOSE: To develop a generalized signal model for dual-module velocity-selective arterial spin labeling (dm-VSASL) that can integrate arbitrary saturation and inversion profiles. THEORY AND METHODS: A recently developed mathematical framework for single-module VSASL is extended to address the increased complexity of dm-VSASL and to model the use of realistic velocity-selective profiles in the label-control and vascular crushing modules. Expressions for magnetization difference, arterial delivery functions, labeling efficiency, and cerebral blood flow (CBF) estimation error are presented. Sources of error are examined and timing requirements to minimize quantification errors are derived. RESULTS: For ideal velocity-selective profiles, the predicted signals match those of prior work. With realistic profiles, a CBF-dependent estimation error can occur when velocity-selective inversion (VSI) is used for the labeling modules and velocity-selective saturation (VSS) is used for the vascular crushing module. The error reflects a mismatch between the leading and trailing edges of the delivery function for the second bolus and can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal saturation cutoff velocity. In the presence of B 0 $$ {\mathrm{B}}_0 $$ and B 1 $$ {\mathrm{B}}_1 $$ inhomogeneities, the labeling efficiency of dual-module VSI is more attenuated than that of dual-module VSS. CONCLUSION: The proposed signal model will enable researchers to more accurately assess and compare the performance of realistic dm-VSASL implementations and improve the quantification of dm-VSASL CBF measures.

A mathematical model for velocity-selective arterial spin labeling.

PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Multicenter comparison using two AI stroke CT perfusion software packages for determining thrombectomy eligibility.

BACKGROUND: Stroke AI platforms assess infarcted core and potentially salvageable tissue (penumbra) to identify patients suitable for mechanical thrombectomy. Few studies have compared outputs of these platforms, and none have been multicenter or considered NIHSS or scanner/protocol differences. Our objective was to compare volume estimates and thrombectomy eligibility from two widely used CT perfusion (CTP) packages, Viz.ai and RAPID.AI, in a large multicenter cohort. METHODS: We analyzed CTP data of acute stroke patients with large vessel occlusion (LVO) from four institutions. Core and penumbra volumes were estimated by each software and DEFUSE-3 thrombectomy eligibility assessed. Results between software packages were compared and categorized by NIHSS score, scanner manufacturer/model, and institution. RESULTS: Primary analysis of 362 cases found statistically significant differences in both software's volume estimations, with subgroup analysis showing these differences were driven by results from a single scanner model, the Canon Aquilion One. Viz.ai provided larger estimates with mean differences of 8cc and 18cc for core and penumbra, respectively (p<0.001). NIHSS subgroup analysis also showed systematically larger Viz.ai volumes (p<0.001). Despite volume differences, a significant difference in thrombectomy eligibility was not found. Additional subgroup analysis showed significant differences in penumbra volume for the Phillips Ingenuity scanner, and thrombectomy eligibility for the Canon Aquilion One scanner at one center (7 % increased eligibility with Viz.ai, p=0.03). CONCLUSIONS: Despite systematic differences in core and penumbra volume estimates between Viz.ai and RAPID.AI, DEFUSE-3 eligibility was not statistically different in primary or NIHSS subgroup analysis. A DEFUSE-3 eligibility difference, however, was seen on one scanner at one institution, suggesting scanner model and local CTP protocols can influence performance and cause discrepancies in thrombectomy eligibility. We thus recommend centers discuss optimal scanning protocols with software vendors and scanner manufacturers to maximize CTP accuracy.

Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.

This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.

VESPA ASL: VElocity and SPAtially Selective Arterial Spin Labeling.

PURPOSE: Spatially selective arterial spin labeling (ASL) perfusion MRI is sensitive to arterial transit times (ATT) that can result in inaccurate perfusion quantification when ATTs are long. Velocity-selective ASL is robust to this effect because blood is labeled within the imaging region, allowing immediate label delivery. However, velocity-selective ASL cannot characterize ATTs, which can provide important clinical information. Here, we introduce a novel pulse sequence, called VESPA ASL, that combines velocity-selective and pseudo-continuous ASL to simultaneously label different pools of arterial blood for robust cerebral blood flow (CBF) and ATT measurement. METHODS: The VESPA ASL sequence is similar to velocity-selective ASL, but the velocity-selective labeling is made spatially selective, and pseudo-continuous ASL is added to fill the inflow time. The choice of inflow time and other sequence settings were explored. VESPA ASL was compared to multi-delay pseudo-continuous ASL and velocity-selective ASL through simulations and test-retest experiments in healthy volunteers. RESULTS: VESPA ASL is shown to accurately measure CBF in the presence of long ATTs, and ATTs < TI can also be measured. Measurements were similar to established ASL techniques when ATT was short. When ATT was long, VESPA ASL measured CBF more accurately than multi-delay pseudo-continuous ASL, which tended to underestimate CBF. CONCLUSION: VESPA ASL is a novel and robust approach to simultaneously measure CBF and ATT and offers important advantages over existing methods. It fills an important clinical need for noninvasive perfusion and transit time imaging in vascular diseases with delayed arterial transit.

Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Recent Technical Developments in ASL: A Review of the State of the Art.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

Apparent posterior cerebral artery territory perfusion asymmetry on arterial spin labeling MRI is a common non-pathologic finding in patients with a unilateral fetal posterior cerebral artery.

PURPOSE: To determine the frequency of apparent posterior cerebral artery (PCA) territory asymmetry seen on arterial spin labeling (ASL) imaging in patients with a unilateral fetal PCA, but without underlying clinical or imaging pathology to suggest true hypoperfusion. METHODS: A search of radiology reports from 1/2017 through 6/2020 was performed with the inclusion term "fetal PCA." Eighty patients were included with unilateral fetal PCA confirmed on MRA or CTA, with brain MRI including ASL imaging, and without conventional imaging abnormality or clinical symptoms referable to the PCA territories. Cases were evaluated by two independent readers for visually apparent PCA perfusion asymmetries. ASL imaging consisted of pseudocontinuous ASL with 1.5 s labeling duration and 2 s post-labeling delay adapted from white paper recommendations. RESULTS: Thirteen of 80 cases (16.2%) had apparent hypoperfusion in the PCA territory contralateral to the side of the fetal PCA. Agreement between readers was near perfect (97.5%, κ = 0.91). This finding was more common in patients who were older, scanned on a 3.0 T magnet, and who had non-visualization of the posterior communicating artery contralateral to the fetal PCA. CONCLUSION: Apparent PCA hypoperfusion on ASL is not uncommon in patients with a contralateral fetal PCA who have no clinical or conventional imaging findings to suggest true hypoperfusion. This phenomenon is likely due to differential blood velocities between the carotid and vertebral arteries that result in differential arterial transit times and labeling efficiency. It is important for radiologists to know that apparent hypoperfusion may arise from variant circle of Willis anatomy.

Clinical utility of arterial spin labeling perfusion images in the emergency department for the work-up of stroke-like symptoms.

PURPOSE: To assess the utility of ASL in evaluating patients presenting to the ED with stroke-like symptoms. METHODS: ASL and DWI images from 526 consecutive patients presenting to the ED with acute stroke symptoms were retrospectively reviewed. DWI images were evaluated for volume of restricted diffusion using ABC/2. ASL maps were evaluated for decreased, normal, or increased signal. The volume of decreased ASL signal was calculated using the same ABC/2 technique. The volume of decreased ASL signal was correlated with the volume of DWI signal abnormality to identify cases of mismatch (DWI:ASL ratio > 1.8) and to correlate this mismatch with infarct growth on imaging follow-up. NIHSS, length of hospital stay, mRS, and future admission for acute stroke-like symptoms were recorded. Correlations between ASL abnormalities and clinical parameters were evaluated using a two-tailed t-test. RESULTS: Of the 526 patients presenting with acute stroke symptoms, 136 patients had an abnormal ASL scan and 388 patients had a normal ASL scan. Of the 136 patients with abnormal ASL, 84 patients had low ASL signal with 79 of these being related to acute infarcts. Elevated ASL signal was seen in 52 patients, of which 30 of these patients had reperfusion hyperemia related to acute infarctions. ASL had a negative predictive value of 94% for evaluating patients with acute ischemic stroke. A subset of patients with abnormal ASL scans with a discharge diagnosis of acute infarction were found to have an ASL:DWI mismatch (ratio > 1.8) and demonstrated significant lesion growth on follow-up imaging (57%). This included some patients who exhibited low ASL signal before development of diffusion restriction (infarction). CONCLUSION: In patients presenting to the ED with acute stroke symptoms, ASL provides information not available with DWI alone. The NPV of ASL for evaluating patients with acute ischemia was 94%.

Moyamoya Presenting after Whole Body Cryotherapy.

BACKGROUND PURPOSE: Moyamoya syndrome is the progressive stenosis of intracranial carotids with secondary collateralization. Whole body cryotherapy (WBC) involves external cooling and is used in holistic and sports medicine, its neurologic effects are unknown. CASE REPORT: We report a first case of symptoms of moyamoya syndrome presenting following WBC and diagnosed with classic MRI ( "Brush Sign", "Ivy sign") and digital subtracted angiography. CONCLUSION: WBC may provoke symptoms of moyamoya syndrome possibly through hyperventilation or vasoconstriction. Practitioners should be aware of possible consequences of WBC in patients with poor cerebrovascular reserve.

Functional oxygen extraction fraction (OEF) imaging with turbo gradient spin echo QUIXOTIC (Turbo QUIXOTIC).

PURPOSE: QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. METHODS: tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. RESULTS: The average cortical GM OEF was estimated as 0.38 ± 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 ± 0.04 at baseline and 0.35 ± 0.05 during activation, with an average %ΔOEF of -20%. These values are consistent with those of past studies. CONCLUSION: tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event-related functional MRI experiments. Magn Reson Med 79:2713-2723, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Assessing the effects of subject motion on T2 relaxation under spin tagging (TRUST) cerebral oxygenation measurements using volume navigators.

PURPOSE: Subject motion may cause errors in estimates of blood T2 when using the T2 -relaxation under spin tagging (TRUST) technique on noncompliant subjects like neonates. By incorporating 3D volume navigators (vNavs) into the TRUST pulse sequence, independent measurements of motion during scanning permit evaluation of these errors. METHODS: The effects of integrated vNavs on TRUST-based T2 estimates were evaluated using simulations and in vivo subject data. Two subjects were scanned with the TRUST+vNav sequence during prescribed movements. Mean motion scores were derived from vNavs and TRUST images, along with a metric of exponential fit quality. Regression analysis was performed between T2 estimates and mean motion scores. Also, motion scores were determined from independent neonatal scans. RESULTS: vNavs negligibly affected venous blood T2 estimates and better detected subject motion than fit quality metrics. Regression analysis showed that T2 is biased upward by 4.1 ms per 1 mm of mean motion score. During neonatal scans, mean motion scores of 0.6 to 2.0 mm were detected. CONCLUSION: Motion during TRUST causes an overestimate of T2 , which suggests a cautious approach when comparing TRUST-based cerebral oxygenation measurements of noncompliant subjects. Magn Reson Med 78:2283-2289, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Purpose: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Methods: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. Results: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). Conclusions: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

Phase-based regional oxygen metabolism (PROM) using MRI.

Venous oxygen saturation (Y(v) ) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO(2)) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Y(v) and CMRO(2) using noninvasive imaging. This article proposes a technique to quantify CMRO(2) from independent MRI estimates of Y(v) and cerebral blood flow. The approach uses standard gradient-echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient-echo phase images, Y(v) was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Fick's principle of arteriovenous difference was then used to quantify CMRO(2) locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% ± 2.3% for Y(v), 51.7 ± 6.4 mL/100 g/min for cerebral blood flow, and 158 ± 18 µmol/100 g/min for CMRO(2) (mean ± SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI.

Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity.

PURPOSE: To compare the performance of pulsed and pseudocontinuous arterial spin-labeling (PASL and pCASL) methods in measuring CO(2) -induced cerebrovascular reactivity (CVR). MATERIALS AND METHODS: Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO(2) -induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end-tidal PCO(2) . Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal-to-noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t-tests. RESULTS: Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL). CONCLUSION: pCASL may be less prone to underestimation of CO(2) -induced flow changes due to improved label timing control.