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.

Longitudinal Alterations of Cerebral Blood Flow in High-Contact Sports.

OBJECTIVE: Repetitive head trauma is common in high-contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes. METHODS: We prospectively studied 63 American football (high-contact cohort) and 34 volleyball (low-contact controls) male collegiate athletes, tracking CBF using 3D pseudocontinuous arterial spin labeling magnetic resonance imaging for up to 4 years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co-registering to T1-weighted images. A linear mixed effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position-based head impact risk and baseline Standardized Concussion Assessment Tool score. Additionally, we evaluated early (1-5 days) and delayed (3-6 months) post-concussion rCBF changes (in-study concussion). RESULTS: Supratentorial gray matter rCBF declined in football compared with volleyball (sport-time interaction p = 0.012), with a strong effect in the parietal lobe (p = 0.002). Football players with higher position-based impact-risk had lower occipital rCBF over time (interaction p = 0.005), whereas players with lower baseline Standardized Concussion Assessment Tool score (worse performance) had relatively decreased rCBF in the cingulate-insula over time (interaction effect p = 0.007). Both cohorts showed a left-right rCBF asymmetry that decreased over time. Football players with an in-study concussion showed an early increase in occipital lobe rCBF (p = 0.0166). INTERPRETATION: These results suggest head impacts may result in an early increase in rCBF, but cumulatively a long-term decrease in rCBF. ANN NEUROL 2023;94:457-469.

Measuring Quantitative Cerebral Blood Flow in Healthy Children: A Systematic Review of Neuroimaging Techniques.

Cerebral blood flow (CBF) is an important hemodynamic parameter to evaluate brain health. It can be obtained quantitatively using medical imaging modalities such as magnetic resonance imaging and positron emission tomography (PET). Although CBF in adults has been widely studied and linked with cerebrovascular and neurodegenerative diseases, CBF data in healthy children are sparse due to the challenges in pediatric neuroimaging. An understanding of the factors affecting pediatric CBF and its normal range is crucial to determine the optimal CBF measuring techniques in pediatric neuroradiology. This review focuses on pediatric CBF studies using neuroimaging techniques in 32 articles including 2668 normal subjects ranging from birth to 18 years old. A systematic literature search was conducted in PubMed, Embase, and Scopus and reported following the preferred reporting items for systematic reviews and meta-analyses (PRISMA). We identified factors (such as age, gender, mood, sedation, and fitness) that have significant effects on pediatric CBF quantification. We also investigated factors influencing the CBF measurements in infants. Based on this review, we recommend best practices to improve CBF measurements in pediatric neuroimaging. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Short- and Long-Term MRI Assessed Hemodynamic Changes in Pediatric Moyamoya Patients After Revascularization.

BACKGROUND: Cerebrovascular reserve (CVR) reflects the capacity of cerebral blood flow (CBF) to change following a vasodilation challenge. Decreased CVR is associated with a higher stroke risk in patients with cerebrovascular diseases. While revascularization can improve CVR and reduce this risk in adult patients with vasculopathy such as those with Moyamoya disease, its impact on hemodynamics in pediatric patients remains to be elucidated. Arterial spin labeling (ASL) is a quantitative MRI technique that can measure CBF, CVR, and arterial transit time (ATT) non-invasively. PURPOSE: To investigate the short- and long-term changes in hemodynamics after bypass surgeries in patients with Moyamoya disease. STUDY TYPE: Longitudinal. POPULATION: Forty-six patients (11 months-18 years, 28 females) with Moyamoya disease. FIELD STRENGTH/SEQUENCE: 3-T, single- and multi-delay ASL, T1-weighted, T2-FLAIR, 3D MRA. ASSESSMENT: Imaging was performed 2 weeks before and 1 week and 6 months after surgical intervention. Acetazolamide was employed to induce vasodilation during the imaging procedure. CBF and ATT were measured by fitting the ASL data to the general kinetic model. CVR was computed as the percentage change in CBF. The mean CBF, ATT, and CVR values were measured in the regions affected by vasculopathy. STATISTICAL TESTS: Pre- and post-revascularization CVR, CBF, and ATT were compared for different regions of the brain. P-values <0.05 were considered statistically significant. RESULTS: ASL-derived CBF in flow territories affected by vasculopathy significantly increased after bypass by 41 ± 31% within a week. At 6 months, CBF significantly increased by 51 ± 34%, CVR increased by 68 ± 33%, and ATT was significantly reduced by 6.6 ± 2.9%. DATA CONCLUSION: There may be short- and long-term improvement in the hemodynamic parameters of pediatric Moyamoya patients after bypass surgery. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Predicting FDG-PET Images From Multi-Contrast MRI Using Deep Learning in Patients With Brain Neoplasms.

BACKGROUND: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is valuable for determining presence of viable tumor, but is limited by geographical restrictions, radiation exposure, and high cost. PURPOSE: To generate diagnostic-quality PET equivalent imaging for patients with brain neoplasms by deep learning with multi-contrast MRI. STUDY TYPE: Retrospective. SUBJECTS: Patients (59 studies from 51 subjects; age 56 ± 13 years; 29 males) who underwent 18 F-FDG PET and MRI for determining recurrent brain tumor. FIELD STRENGTH/SEQUENCE: 3T; 3D GRE T1, 3D GRE T1c, 3D FSE T2-FLAIR, and 3D FSE ASL, 18 F-FDG PET imaging. ASSESSMENT: Convolutional neural networks were trained using four MRIs as inputs and acquired FDG PET images as output. The agreement between the acquired and synthesized PET was evaluated by quality metrics and Bland-Altman plots for standardized uptake value ratio. Three physicians scored image quality on a 5-point scale, with score ≥3 as high-quality. They assessed the lesions on a 5-point scale, which was binarized to analyze diagnostic consistency of the synthesized PET compared to the acquired PET. STATISTICAL TESTS: The agreement in ratings between the acquired and synthesized PET were tested with Gwet's AC and exact Bowker test of symmetry. Agreement of the readers was assessed by Gwet's AC. P = 0.05 was used as the cutoff for statistical significance. RESULTS: The synthesized PET visually resembled the acquired PET and showed significant improvement in quality metrics (+21.7% on PSNR, +22.2% on SSIM, -31.8% on RSME) compared with ASL. A total of 49.7% of the synthesized PET were considered as high-quality compared to 73.4% of the acquired PET which was statistically significant, but with distinct variability between readers. For the positive/negative lesion assessment, the synthesized PET had an accuracy of 87% but had a tendency to overcall. CONCLUSION: The proposed deep learning model has the potential of synthesizing diagnostic quality FDG PET images without the use of radiotracers. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Exploring the performance and explainability of fine-tuned BERT models for neuroradiology protocol assignment.

BACKGROUND: Deep learning has demonstrated significant advancements across various domains. However, its implementation in specialized areas, such as medical settings, remains approached with caution. In these high-stake environments, understanding the model's decision-making process is critical. This study assesses the performance of different pretrained Bidirectional Encoder Representations from Transformers (BERT) models and delves into understanding its decision-making within the context of medical image protocol assignment. METHODS: Four different pre-trained BERT models (BERT, BioBERT, ClinicalBERT, RoBERTa) were fine-tuned for the medical image protocol classification task. Word importance was measured by attributing the classification output to every word using a gradient-based method. Subsequently, a trained radiologist reviewed the resulting word importance scores to assess the model's decision-making process relative to human reasoning. RESULTS: The BERT model came close to human performance on our test set. The BERT model successfully identified relevant words indicative of the target protocol. Analysis of important words in misclassifications revealed potential systematic errors in the model. CONCLUSIONS: The BERT model shows promise in medical image protocol assignment by reaching near human level performance and identifying key words effectively. The detection of systematic errors paves the way for further refinements to enhance its safety and utility in clinical settings.

Role of Brain Imaging in the Prediction of Intracerebral Hemorrhage Following Endovascular Therapy for Acute Stroke.

Currently most acute ischemic stroke patients presenting with a large vessel occlusion are treated with endovascular therapy (EVT), which results in high rates of successful recanalization. Despite this success, more than half of EVT-treated patients are significantly disabled 3 months later partly due to the occurrence of post-EVT intracerebral hemorrhage. Predicting post-EVT intracerebral hemorrhage is important for individualizing treatment strategies in clinical practice (eg, safe initiation of early antithrombotic therapies), as well as in selecting the optimal candidates for clinical trials that aim to reduce this deleterious outcome. Emerging data suggest that brain and vascular imaging biomarkers may be particularly relevant since they provide insights into the ongoing acute stroke pathophysiology. In this review/perspective, we summarize the accumulating literature on the role of cerebrovascular imaging biomarkers in predicting post-EVT-associated intracerebral hemorrhage. We focus on imaging acquired before EVT, during the EVT procedure, and in the early post-EVT time frames when new therapeutic therapies could be tested. Accounting for the complex pathophysiology of post-EVT-associated intracerebral hemorrhage, this review may provide some guidance for future prospective observational or therapeutic studies.

Functional Outcome Prediction in Acute Ischemic Stroke Using a Fused Imaging and Clinical Deep Learning Model.

BACKGROUND: Predicting long-term clinical outcome based on the early acute ischemic stroke information is valuable for prognostication, resource management, clinical trials, and patient expectations. Current methods require subjective decisions about which imaging features to assess and may require time-consuming postprocessing. This study's goal was to predict ordinal 90-day modified Rankin Scale (mRS) score in acute ischemic stroke patients by fusing a Deep Learning model of diffusion-weighted imaging images and clinical information from the acute period. METHODS: A total of 640 acute ischemic stroke patients who underwent magnetic resonance imaging within 1 to 7 days poststroke and had 90-day mRS follow-up data were randomly divided into 70% (n=448) for model training, 15% (n=96) for validation, and 15% (n=96) for internal testing. Additionally, external testing on a cohort from Lausanne University Hospital (n=280) was performed to further evaluate model generalization. Accuracy for ordinal mRS, accuracy within ±1 mRS category, mean absolute prediction error, and determination of unfavorable outcome (mRS score >2) were evaluated for clinical only, imaging only, and 2 fused clinical-imaging models. RESULTS: The fused models demonstrated superior performance in predicting ordinal mRS score and unfavorable outcome in both internal and external test cohorts when compared with the clinical and imaging models. For the internal test cohort, the top fused model had the highest area under the curve of 0.92 for unfavorable outcome prediction and the lowest mean absolute error (0.96 [95% CI, 0.77-1.16]), with the highest proportion of mRS score predictions within ±1 category (79% [95% CI, 71%-88%]). On the external Lausanne University Hospital cohort, the best fused model had an area under the curve of 0.90 for unfavorable outcome prediction and outperformed other models with an mean absolute error of 0.90 (95% CI, 0.79-1.01), and the highest percentage of mRS score predictions within ±1 category (83% [95% CI, 78%-87%]). CONCLUSIONS: A Deep Learning-based imaging model fused with clinical variables can be used to predict 90-day stroke outcome with reduced subjectivity and user burden.

Predicting Hypoperfusion Lesion and Target Mismatch in Stroke from Diffusion-weighted MRI Using Deep Learning.

Background Perfusion imaging is important to identify a target mismatch in stroke but requires contrast agents and postprocessing software. Purpose To use a deep learning model to predict the hypoperfusion lesion in stroke and identify patients with a target mismatch profile from diffusion-weighted imaging (DWI) and clinical information alone, using perfusion MRI as the reference standard. Materials and Methods Imaging data sets of patients with acute ischemic stroke with baseline perfusion MRI and DWI were retrospectively reviewed from multicenter data available from 2008 to 2019 (Imaging Collaterals in Acute Stroke, Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2, and University of California, Los Angeles stroke registry). For perfusion MRI, rapid processing of perfusion and diffusion software automatically segmented the hypoperfusion lesion (time to maximum, ≥6 seconds) and ischemic core (apparent diffusion coefficient [ADC], ≤620 × 10-6 mm2/sec). A three-dimensional U-Net deep learning model was trained using baseline DWI, ADC, National Institutes of Health Stroke Scale score, and stroke symptom sidedness as inputs, with the union of hypoperfusion and ischemic core segmentation serving as the ground truth. Model performance was evaluated using the Dice score coefficient (DSC). Target mismatch classification based on the model was compared with that of the clinical-DWI mismatch approach defined by the DAWN trial by using the McNemar test. Results Overall, 413 patients (mean age, 67 years ± 15 [SD]; 207 men) were included for model development and primary analysis using fivefold cross-validation (247, 83, and 83 patients in the training, validation, and test sets, respectively, for each fold). The model predicted the hypoperfusion lesion with a median DSC of 0.61 (IQR, 0.45-0.71). The model identified patients with target mismatch with a sensitivity of 90% (254 of 283; 95% CI: 86, 93) and specificity of 77% (100 of 130; 95% CI: 69, 83) compared with the clinical-DWI mismatch sensitivity of 50% (140 of 281; 95% CI: 44, 56) and specificity of 89% (116 of 130; 95% CI: 83, 94) (P < .001 for all). Conclusion A three-dimensional U-Net deep learning model predicted the hypoperfusion lesion from diffusion-weighted imaging (DWI) and clinical information and identified patients with a target mismatch profile with higher sensitivity than the clinical-DWI mismatch approach. ClinicalTrials.gov registration nos. NCT02225730, NCT01349946, NCT02586415 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Kallmes and Rabinstein in this issue.

Effect of vitamin D supplementation on cerebral blood flow in male patients with adrenoleukodystrophy.

One-third of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating lesions, typically at the splenium. These lesions share similarities with multiple sclerosis, including cerebral hypoperfusion and links to vitamin D insufficiency. We hypothesized that increasing vitamin D levels would increase cerebral blood flow (CBF) in ALD boys. We conducted an exploratory analysis of vitamin D supplementation and CBF using all available data from participants enrolled in a recent single-arm interventional study of vitamin D supplementation in boys with ALD. We measured whole brain and splenium CBF using arterial spin labeling (ASL) from three study time points (baseline, 6 months, and 12 months). We used linear generalized estimating equations to evaluate CBF changes between time points and to test for an association between CBF and vitamin D. ASL data were available for 16 participants, aged 2-22 years. Mean vitamin D levels increased by 72.7% (p < .001) after 6 months and 88.6% (p < .01) after 12 months. Relative to baseline measures, mean CBF of the whole brain (6 months: +2.5%, p = .57; 12 months: +6.1%, p = .18) and splenium (6 months: +1.2%, p = .80; 12 months: +7.4%, p = .058) were not significantly changed. Vitamin D levels were positively correlated with CBF in the splenium (slope = .59, p < .001). In this exploratory analysis, we observed a correlation between vitamin D levels and splenial CBF in ALD boys. We confirm the feasibility of measuring CBF in this brain region and population, but further work is needed to establish a causal role for vitamin D in modulating CBF.

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.

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Reducing Gadolinium Contrast With Artificial Intelligence.

Gadolinium contrast is an important agent in magnetic resonance imaging (MRI), particularly in neuroimaging where it can help identify blood-brain barrier breakdown from an inflammatory, infectious, or neoplastic process. However, gadolinium contrast has several drawbacks, including nephrogenic systemic fibrosis, gadolinium deposition in the brain and bones, and allergic-like reactions. As computer hardware and technology continues to evolve, machine learning has become a possible solution for eliminating or reducing the dose of gadolinium contrast. This review summarizes the clinical uses of gadolinium contrast, the risks of gadolinium contrast, and state-of-the-art machine learning methods that have been applied to reduce or eliminate gadolinium contrast administration, as well as their current limitations, with a focus on neuroimaging applications. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Amyloid-Related Imaging Abnormalities: An Update.

Amyloid-related imaging abnormalities (ARIA) is a term introduced in 2010 to encompass a spectrum of MRI findings observed in patients receiving investigational anti-amyloid beta (Aß) immunotherapies for Alzheimer disease (AD). The entity can be broadly categorized into ARIA characterized by edema and effusion (ARIA-E) and ARIA characterized by microhemorrhages and superficial siderosis (ARIA-H). ARIA typically occurs early in the treatment course and has a higher incidence in patients who are apolipoprotein E ε4 allele carriers. ARIA-E has an additional dose dependence, with higher incidence in patients receiving higher doses of anti-Aß immuno-therapies. ARIA is often asymptomatic and self-resolving. The recognition of ARIA has implications for patient selection and monitoring for Aß immunotherapies, and its development can potentially lead to a pause or discontinuation of therapy. The FDA's first approval of an Aß-targeting monoclonal antibody for AD treatment in 2021 will lead to such therapy's expanded use beyond the clinical trial setting and to radiologists more commonly encountering ARIA in clinical practice. This review explores the theorized pathophysiologic mechanisms for ARIA, describes the MRI findings and grading schemes for ARIA-E and AREA-H, and summarizes relevant Aß immunotherapies. Through such knowledge, radiologists can optimally impact the management of patients receiving targeted AD therapies.

18F-FSPG PET/CT Imaging of System xC- Transporter Activity in Patients with Primary and Metastatic Brain Tumors.

Background The PET tracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) targets the system xC- cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors (n = 17) or brain metastases (n = 9) were enrolled in this prospective, single-center study (ClinicalTrials.gov identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18F-FSPG PET/CT scan and a static whole-body (WB) 18F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 (18F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18F-FDG PET was performed, 18F-FSPG permitted visualization of non-18F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant Ki and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group (P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.

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.

Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure.

RATIONALE & OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in individuals with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial (SPRINT) who underwent brain magnetic resonance imaging studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP <120 mm Hg) versus standard (systolic BP <140 mm Hg) BP lowering. OUTCOMES: The magnetic resonance imaging outcome measures were the 4-year change in global cerebral blood flow (CBF), white matter lesion (WML) volume, and total brain volume (TBV). RESULTS: A total of 716 randomized participants with a mean age of 68 years were enrolled; follow-up imaging occurred after a median 3.9 years. Among participants with eGFR <60 mL/min/1.73 m2 (n = 234), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 3.38 (95% CI, 0.32 to 6.44) mL/100 g/min, -0.06 (95% CI, -0.16 to 0.04) cm3 (inverse hyperbolic sine-transformed), and -3.8 (95% CI, -8.3 to 0.7) cm3, respectively. Among participants with UACR >30 mg/g (n = 151), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 1.91 (95% CI, -3.01 to 6.82) mL/100 g/min, 0.003 (95% CI, -0.13 to 0.13) cm3 (inverse hyperbolic sine-transformed), and -7.0 (95% CI, -13.3 to -0.3) cm3, respectively. The overall treatment effects on CBF and TBV were not modified by baseline eGFR or UACR; however, the effect on WMLs was attenuated in participants with albuminuria (P = 0.04 for interaction). LIMITATIONS: Measurement variability due to multisite design. CONCLUSIONS: Among adults with hypertension who have primarily early kidney disease, intensive versus standard BP treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive BP treatment targets on brain health in persons with early kidney disease. FUNDING: SPRINT was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with study number NCT01206062.

Predicting Infarct Core From Computed Tomography Perfusion in Acute Ischemia With Machine Learning: Lessons From the ISLES Challenge.

BACKGROUND AND PURPOSE: The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally diverse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard. METHODS: The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance. RESULTS: Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180-238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25-79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7-45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team's algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3; volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance. CONCLUSIONS: Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.

Cerebrovascular reactivity measurements using simultaneous 15O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging.

BACKGROUND: Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. METHODS: We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. RESULTS: The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). CONCLUSIONS: Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).