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Background: Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS), whether anomalous NVC would be present is unclear. Purpose: To investigate NVC changes and potential neural basis in MELAS by combining resting‐state functional MRI (rs‐fMRI) and arterial spin labeling (ASL). Study Type: Prospective. Subjects: Twenty‐four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. Field Strength/Sequence: 3.0 T, resting‐state gradient‐recalled echo‐planar imaging and pseudo‐continuous 3D ASL sequences. Assessment: Amplitude of low‐frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs‐fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF‐ALFF, CBF‐fALFF, CBF‐ReHo, and CBF‐FCS. Regional NVC was also evaluated by voxel‐wise and lesion‐wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. Statistical Tests: Two‐sample t‐test, paired‐sample t‐test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. Results: Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF‐ALFF, CBF‐fALFF, CBF‐ReHo, and CBF‐FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke‐like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. Data Conclusions: This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background: Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non‐invasive technique that assesses tissue perfusion. Purpose: To assess the utility of ASL for the discrimination of patients with post‐transplant allograft dysfunction who do not need biopsy from those who need. Study Type: Prospective. Subjects: Forty‐six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group). Field Strength/Sequence: 3.0 T and 3D fast‐spin echo sequence. Assessment: All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups. Statistical Analyses: Chi‐square test, independent student t‐test, Mann–Whitney U test, receiver‐operating characteristic curve. A two‐tailed P < 0.05 denoted statistical significance. Results: The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4–8] vs. 1 [0–2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96–134.92] mL/min/100 g vs. 153.48 [113.19–160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL. Data Conclusion: The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy. Level of Evidence: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Background: The blood–brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in the BBB occurring with healthy aging. Purpose: To investigate age‐related changes in the BBB permeability to water using multiple‐echo‐time (multi‐TE) arterial spin labeling (ASL) MRI. Study Type: Prospective, cohort. Population: Two groups of healthy humans—older group (≥50 years, mean age = 56 ± 4 years, N = 13, females = 5) and younger group (≤20 years, mean age = 18 ± 1, N = 13, females = 7). Field Strength/Sequence: A 3T, multi‐TE Hadamard pCASL with 3D Gradient and Spin Echo (GRASE) readout. Assessment: Two different approaches of variable complexity were applied. A physiologically informed biophysical model with a higher complexity estimating time (Tex) taken by the labeled water to move across the BBB and a simpler model of triexponential decay measuring tissue transition rate (klin). Statistics: Two‐tailed unpaired Student t‐test, Pearson's correlation coefficient and effect size. P < 0.05 was considered significant. Results: Older volunteers showed significant differences of 36% lower Tex, 29% lower cerebral perfusion, 17% pronged arterial transit time and 22% shorter intra‐voxel transit time compared to the younger volunteers. Tissue fraction (fEV) at the earliest TI = 1600 msec was significantly higher in the older group, which contributed to a significantly lower klin compared to the younger group. fEV at TI = 1600 msec showed significant negative correlation with Tex (r = −0.80), and klin and Tex showed significant positive correlation (r = 0.73). Data Conclusions: Both approaches of Multi‐TE ASL imaging showed sensitivity to detect age‐related changes in the BBB permeability. High tissue fractions at the earliest TI and short Tex in the older volunteers indicate that the BBB permeability increased with age. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

BackgroundWhile evaluation of blood perfusion in lumbar paraspinal muscles is of interest in low back pain, it has not been performed using noncontrast magnetic resonance (MR) techniques.PurposeTo introduce a novel application of a time-resolved, noncontrast MR perfusion technique for paraspinal muscles and demonstrate effect of exercise on perfusion parameters.Study typeLongitudinal.SubjectsSix healthy subjects (27-48 years old, two females) and two subjects with acute low back pain (46 and 65 years old females, one with diabetes/obesity).Field strength/sequence3-T, MR perfusion sequence.AssessmentLumbar spines of healthy subjects were imaged axially at L3 level with a tag-on and tag-off alternating inversion recovery arterial spin labeling technique that suppresses background signal and acquires signal increase ratio (SIR) from the in-flow blood at varying inversion times (TI) from 0.12 seconds to 3.5 seconds. SIR vs. TI data were fit to determine the perfusion metrics of peak height (PH), time to peak (TTP), mean transit time, apparent muscle blood volume (MBV), and apparent muscle blood flow (MBF) in iliocostal, longissimus, and multifidus. Imaging was repeated immediately after healthy subjects performed a 20-minute walk, to determine the effect of exercise.Statistical testsRepeated measures analysis of variance.ResultsSIR vs. TI data showed well-defined leading and trailing edges, with sharply increasing SIR to TI of approximately 500 msec subsiding quickly to near zero around TI of 1500 msec. After exercise, the mean SIR at every TI increased markedly, resulting in significantly higher PH, MBV, and MBF (each P  28.9), and a lower TTP (P

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 [ABSTRACT FROM AUTHOR]

Background: Cerebral perfusion is directly affected by systemic blood pressure, which has been shown to be negatively correlated with cerebral blood flow (CBF). The impact of aging on these effects is not fully understood. Purpose: To determine whether the relationship between mean arterial pressure (MAP) and cerebral hemodynamics persists throughout the lifespan. Study Type: Retrospective, cross‐sectional study. Population: Six hundred and sixty‐nine participants from the Human Connectome Project‐Aging ranging between 36 and 100+ years and without a major neurological disorder. Field Strength/Sequence: Imaging data was acquired at 3.0 Tesla using a 32‐channel head coil. CBF and arterial transit time (ATT) were measured by multi‐delay pseudo‐continuous arterial spin labeling. Assessment: The relationships between cerebral hemodynamic parameters and MAP were evaluated globally in gray and white matter and regionally using surface‐based analysis in the whole group, separately within different age groups (young: <60 years; younger‐old: 60–79 years; oldest‐old: ≥80 years). Statistical Tests: Chi‐squared, Kruskal‐Wallis, ANOVA, Spearman rank correlation and linear regression models. The general linear model setup in FreeSurfer was used for surface‐based analyses. P < 0.05 was considered significant. Results: Globally, there was a significant negative correlation between MAP and CBF in both gray (ρ = −0.275) and white matter (ρ = −0.117). This association was most prominent in the younger‐old [gray matter CBF (β = −0.271); white matter CBF (β = −0.241)]. In surface‐based analyses, CBF exhibited a widespread significant negative association with MAP throughout the brain, whereas a limited number of regions showed significant prolongation in ATT with higher MAP. The associations between regional CBF and MAP in the younger‐old showed a different topographic pattern in comparison to young subjects. Data Conclusion: These observations further emphasize the importance of cardiovascular health in mid‐to‐late adulthood for healthy brain aging. The differences in the topographic pattern with aging indicate a spatially heterogeneous relationship between high blood pressure and CBF. Level of Evidence: 3 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

Background: Multidelay arterial spin labeling (ASL) generates time‐resolved perfusion maps, which may provide sufficient and accurate hemodynamic information in carotid stenosis. Purpose: To use imaging markers derived from multidelay ASL magnetic resonance imaging (MRI) and to determine the optimal strategy for predicting cerebral hyperperfusion after carotid endarterectomy (CEA). Study Type: Prospective observational cohort. Subjects: A total of 79 patients who underwent CEA for carotid stenosis. Field Strength/Sequence: A 3.0 T/pseudo‐continuous ASL with three postlabeling delays of 1.0, 1.57, and 2.46 seconds using fast‐spin echo readout. Assessment: Cerebral perfusion pressure, antegrade, and collateral flow were scored on a four‐grade ordinal scale based on preoperative multidelay ASL perfusion maps. Simultaneously, quantitative hemodynamic parameters including cerebral blood flow (CBF), arterial transit time (ATT), relative CBF (rCBF) and relative ATT (rATT; ipsilateral/contralateral values) were calculated. On the CBF ratio map obtained through dividing postoperative by preoperative CBF map, regions of interest were placed covering ipsilateral middle cerebral artery territory. Three neuroradiologists conducted this procedure. Cerebral hyperperfusion was defined as a CBF ratio >2. Statistical Tests: Weighted κ values, independent sample t test, chi‐square test, Mann–Whitney U‐test, multivariable logistic regression analysis, receiver‐operating characteristic curve analysis, and Delong test. Significance level was P < 0.05. Results: Cerebral hyperperfusion was observed in 15 (19%) patients. Higher blood pressure (odd ratio [OR] = 1.08) and carotid near‐occlusion (NO; OR = 7.31) were clinical risk factors for postoperative hyperperfusion. Poor ASL perfusion score (OR = 37.33), decreased CBF (OR = 0.74), prolonged ATT (OR = 1.02), lower rCBF (OR = 0.91), and higher rATT (OR = 1.12) were independent imaging predictors of hyperperfusion. ASL perfusion score exhibited the highest specificity (95.3%), while CBF exhibited the highest sensitivity (93.3%) for the prediction of hyperperfusion. When combined with ASL perfusion score, CBF and ATT, the predictive ability was significantly higher than using blood pressure and NO alone (AUC: 0.98 vs. 0.78). Data Conclusions: Multidelay ASL can accurately predict cerebral hyperperfusion after CEA with high sensitivity and specificity. Evidence Level: 2 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Background: In patients with suspected coronary artery disease (CAD), myocardial perfusion is assessed under rest and pharmacological stress to identify ischemia. Splenic switch‐off, defined as the stress to rest splenic perfusion attenuation in response to adenosine, has been proposed as an indicator of stress adequacy. Its occurrence has been previously assessed in first‐pass perfusion images, but the use of noncontrast techniques would be highly beneficial. Purpose: To explore the ability of pseudo‐continuous arterial spin labeling (PCASL) to identify splenic switch‐off in patients with suspected CAD. Study Type: Prospective. Population: Five healthy volunteers (age 24.8 ± 3.8 years) and 32 patients (age 66.4 ± 8.2 years) with suspected CAD. Field strength/Sequence: A 1.5‐T/PCASL (spin‐echo) and first‐pass imaging (gradient‐echo). Assessment: In healthy subjects, multi‐delay PCASL data (500–2000 msec) were acquired to quantify splenic blood flow (SBF) and determine the adequate postlabeling delay (PLD) for single‐delay acquisitions (PLD > arterial transit time). In patients, single‐delay PCASL (1200 msec) and first‐pass perfusion images were acquired under rest and adenosine conditions. PCASL data were used to compute SBF maps and SBF stress‐to‐rest ratios. Three observers classified patients into "switch‐off" and "failed switch‐off" groups by visually comparing rest‐stress perfusion data acquired with PCASL and first‐pass, independently. First‐pass categories were used as reference to evaluate the accuracy of quantitative classification. Statistical Tests: Wilcoxon signed‐rank, Pearson correlation, kappa, percentage agreement, Generalized Linear Mixed Model, Mann–Whitney, Pearson Chi‐squared, receiver operating characteristic, area‐under‐the‐curve (AUC) and confusion matrix. Significance: P value < 0.05. Results: A total of 27 patients (84.4%) experienced splenic switch‐off according to first‐pass categories. Comparison of PCASL‐derived SBF maps during stress and rest allowed assessment of splenic switch‐off, reflected in a reduction of SBF values during stress. SBF stress‐to‐rest ratios showed a 97% accuracy (sensitivity = 80%, specificity = 100%, AUC = 85.2%). Data Conclusion: This study could demonstrate the feasibility of PCASL to identify splenic switch‐off during adenosine perfusion MRI, both by qualitative and quantitative assessments. Evidence Level: 2 Technical Efficacy: 2 [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) has shown potential for the assessment of penumbral tissue in patients with acute ischemic stroke (AIS). The postlabeling delay (PLD) parameter is sensitive to arterial transit delays and influences cerebral blood flow measurements. Purpose: To assess the impact of ASL acquisition at different PLDs for penumbral tissue quantification and to compare their performance regarding assisting patient selection for endovascular treatment with dynamic susceptibility contrast MRI (DSC‐MRI) as the reference method. Study Type: Retrospective. Population: A total of 53 patients (59.98 ± 12.60 years, 32% women) with AIS caused by internal carotid or middle cerebral artery occlusion. Field Strength/Sequence: A 3‐T, three‐dimensional pseudo‐continuous ASL with fast‐spin echo readout. Assessment: Hypoperfusion volume was measured using DSC‐MRI and ASL with PLDs of 1.500 msec and 2.500 msec, respectively. Eligibility for endovascular treatment was retrospectively determined according to the imaging criteria of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial (DEFUSE 3). Statistical Tests: Kruskal–Wallis tests, Bland–Altman plots, Cohen's kappa, and receiver operating characteristic analyses were used. The threshold for statistical significance was set at P ˂ 0.05. Results: Hypoperfusion volume for ASL with a PLD of 1.500 msec was significantly larger than that for DSC‐MRI, while the hypoperfusion volume for a PLD of 2.500 msec was not significantly different from that of DSC‐MRI (P = 0.435). Bland–Altman plots showed that the mean volumetric error between the hypoperfusion volume measured by DSC‐MRI and ASL with PLDs of 1.500/2.500 msec was −107.0 mL vs. 4.49 mL. Cohen's kappa was 0.679 vs. 0.773 for DSC‐MRI and ASL, respectively, with a PLD of 1.500/2.500 msec. The sensitivity and specificity for ASL with a PLD of 1.500/2.500 msec in identifying patients eligible for treatment were 89.74% vs. 97.44% and 92.86% vs. 64.29%, respectively. Data Conclusion: In AIS, PLDs for ASL acquisition may have a considerable impact on the quantification of the hypoperfusion volume. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

BackgroundWith the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment.Purpose/hypothesisTo evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up.Study typeProspective longitudinal study with a 4-year time interval.Population309 healthy subjects aged 20-89 years old.Field strength/sequence3T pseudo-continuous-arterial-spin-labeling MRI.AssessmentCBF at baseline and cognitive assessment at both baseline and follow-up.Statistical testsLinear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates.ResultsLinear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ≥54 years, β = 0.221, P = 0.004), but not in younger or entire sample (β = 0.018, P = 0.867 and β = 0.089, P = 0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (β = 0.244 P = 0.001), episodic memory (β = 0.294, P = 0.001), and reasoning (β = 0.186, P = 0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition.Data conclusionIn a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function.Level of evidence1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.

PurposeTo compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL).Materials and methodsMonte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared. Pairwise t-tests with Bonferroni correction were used.ResultsThe simulations and in vivo experiments showed that 1-del. PCASL underestimated GM CBF due to insufficient postlabeling delay (PLD) (37.2 ± 8.1 vs. 47.3 ± 8.5 and 47.3 ± 9.0 ml/100g/min, P ≤ 6.5 × 10-6 ), while 5-del. Seq. and 7-del. Had. yielded comparable GM CBF (P ≥ 0.49). 5-del. Seq. was more reproducible for CBF (P = 4.7 × 10-4 ), while 7-del. Had. was more reproducible for ATT (P = 0.033). 5-del. Seq. was more prone to intravascular artifacts and yielded lower GM ATTs compared to 7-del. Had. without crushing (1.13 ± 0.18 vs. 1.23 ± 0.13 seconds, P = 2.3 × 10-3 ), but they gave comparable ATTs with crushing (P = 0.12). ATTs measured with crushing were longer than those without crushing (P ≤ 6.7 × 10-4 ), but CBF was not affected (P ≥ 0.16).ConclusionThe theoretical signal-to-noise ratio (SNR) gain through Hadamard encoding was confirmed experimentally. For 1-del., a PLD of 1.8 seconds is recommended for healthy subjects. With current parameters, 5-del. Seq. was more reproducible for CBF, and 7-del. Had. for ATT. Vascular crushing may help reduce variations in multidelay experiments without compromising tissue CBF or ATT measurements.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1119-1132.

Background: Venous blood oxygenation (Yv), which can be derived from venous blood T2 (T2b), combined with oxygen‐extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T2‐Prepared‐Blood‐Relaxation‐Imaging‐with‐Inversion‐Recovery (T2‐TRIR) was introduced allowing for simultaneous measurements of blood T2 and T1 (T1b), potentially improving Yv estimation by overcoming the need to estimate hematocrit. Purpose: To optimize and compare T2‐TRIR with T2‐relaxation‐under‐spin‐tagging (TRUST) sequence. Study Type: Prospective. Population: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old). Field Strength/Sequence: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE). Assessment: T2b, Yv, and OEF from TRUST and T2‐TRIR were compared and T2‐TRIR‐derived T1b was assessed. Within‐ and between‐session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients. Statistical Tests: Shapiro–Wilk, one‐sample and paired‐sample t‐test, repeated measures ANOVA, mixed linear model, Bland–Altman analysis and correlation analysis. Sidak multiple‐comparison correction was performed. Significance level was 0.05. Results: In controls, T2b from T2‐TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T2b values were lower pre‐ compared to post‐ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T2‐TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre‐ compared to post‐ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T2‐TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T2‐TRIR OEF: 25% ± 8% and 18% ± 6%). Data Conclusion: TRUST and T2‐TRIR are reproducible, but T2‐TRIR‐derived T2b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Noninvasive cerebral blood flow (CBF) monitoring using arterial spin labeling (ASL) magnetic resonance imaging is useful for managing large cerebral artery steno‐occlusive diseases. However, knowledge about its measurement characteristics in comparison with reference standard perfusion imaging is limited. Purpose: To evaluate perfusion in a longitudinal manner in patients with steno‐occlusive disease using ASL and compare with single‐photon emission computed tomography (SPECT). Study Type: Prospective. Population: Moyamoya (n = 10, eight females) and atherosclerotic diseases (n = 2, two males). Field Strength/Sequence: 3.0 T; gradient‐echo three‐dimensional T1‐weighted and spin‐echo ASL. Assessment: Multi‐delay ASL and [123I]‐iodoamphetamine SPECT CBF measurements were performed both before and within 9 days of anterior‐circulation revascularization. Reliability and sensitivity to whole‐brain voxel‐wise CBF changes (ΔCBF) and their postlabeling delay (PLD) dependency with varied PLDs (in milliseconds) of 1000, 2333, and 3666 were examined. Statistical Tests: Reliability and sensitivity to ΔCBF were examined using within‐subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, standard deviation of longitudinal ΔCBF within the hemisphere contralateral to surgery, and the ratio between it and average ΔCBF within the ipsilateral regions of interest were subjected to paired t tests, respectively. P < 0.05 was considered statistically significant. Results: ASL test–retest time interval was 31 ± 18 days. Test–retest reliability was significantly lower for SPECT (0.16 ± 0.02) than ASL (0.13 ± 0.04). Sensitivity to postoperative changes was significantly higher for ASL (2.71 ± 2.79) than SPECT (0.27 ± 0.62). Test–retest reliability was significantly higher for a PLD of 2333 (0.13 ± 0.04) than 3666 (0.19 ± 0.05), and sensitivity to ΔCBF was significantly higher for PLDs of 1000 (2.53 ± 2.50) and 2333 than 3666 (0.79 ± 1.88). ICC maps also showed higher reliability for ASL than SPECT. Data Conclusion: Higher test–retest reliability led to better ASL sensitivity than SPECT for postoperative ΔCBF. ASL test–retest reliability and sensitivity to ΔCBF were higher with a PLD of 2333. Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) has been proven to be effective in ischemia‐induced acute kidney injury (AKI); however, validation of ASL magnetic resonance imaging (MRI) is limited in AKI in the presence of cirrhosis. Purpose: To investigate the feasibility of ASL in revealing renal blood flow (RBF) changes in kidney injury in the presence of cirrhosis and to assess its value in the early diagnosis of disease. Study Type: Longitudinal. Animal Model: Rats were randomized into baseline group (N = 3), sham surgery group (N = 18), and common bile duct ligation (BDL) group (N = 48). All groups were divided into six subgroups based on different sacrificed time points. Field Strength/Sequence: 3 T scanner, prototypic pulsed ASL sequence using flow‐sensitive alternating inversion recovery preparation, half‐Fourier acquisition single‐shot turbo spin echo sequence. Assessment: RBF measurement was performed by ASL. Hematoxylin–eosin (HE) score, Hypoxia‐inducible factor‐1alpha (HIF‐1α) score, peritubular capillar (PTC) density, alanine aminotransferase, aspartate aminotransferase, serum total bilirubin, total bile acids, serum creatinine (Scr), and blood urea nitrogen (BUN) were harvested. Statistical Tests: Analysis of variance, Pearson's correlation coefficient, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. Results: RBF, HE score, HIF‐1α score, and PTC density after BDL were significantly different from baseline. RBF was highly correlated with HE score, HIF‐1α score, and PTC density (r = −0.7598, r = −0.7434, r = 0.6406, respectively). RBF and Scr began to differ significantly from baseline at day 3 and 7 after intervention, respectively. The areas under the curves of RBF, Scr, and BUN for distinguishing non‐AKI from AKI in cirrhosis were 1.00, 0.888, and 0.911, while those for distinguishing mild from severe kidney injury were 0.961, 0.830, and 0.857, respectively. Data Conclusion: ASL allows the longitudinal assessment of the degree of AKI induced by cholestatic cirrhosis in rats and can serve as a noninvasive marker for the early and accurate diagnosis of AKI. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background: Renal blood flow (RBF) can be measured with dynamic contrast enhanced‐MRI (DCE‐MRI) and arterial spin labeling (ASL). Unfortunately, individual estimates from both methods vary and reference‐standard methods are not available. A potential solution is to include a third, arbitrating MRI method in the comparison. Purpose To compare RBF estimates between ASL, DCE, and phase contrast (PC)‐MRI. Study Type: Prospective. Population Twenty‐five patients with type‐2 diabetes (36% female) and five healthy volunteers (HV, 80% female). Field Strength/Sequences: A 3 T; gradient‐echo 2D‐DCE, pseudo‐continuous ASL (pCASL) and cine 2D‐PC. Assessment ASL, DCE, and PC were acquired once in all patients. ASL and PC were acquired four times in each HV. RBF was estimated and split‐RBF was derived as (right kidney RBF)/total RBF. Repeatability error (RE) was calculated for each HV, RE = 1.96 × SD, where SD is the standard deviation of repeat scans. Statistical Tests: Paired t‐tests and one‐way analysis of variance (ANOVA) were used for statistical analysis. The 95% confidence interval (CI) for difference between ASL/PC and DCE/PC was assessed using two‐sample F‐test for variances. Statistical significance level was P < 0.05. Influential outliers were assessed with Cook's distance (Di > 1) and results with outliers removed were presented. Results: In patients, the mean RBF (mL/min/1.73m2) was 618 ± 62 (PC), 526 ± 91 (ASL), and 569 ± 110 (DCE). Differences between measurements were not significant (P = 0.28). Intrasubject agreement was poor for RBF with limits‐of‐agreement (mL/min/1.73m2) [−687, 772] DCE‐ASL, [−482, 580] PC‐DCE, and [−277, 460] PC‐ASL. The difference PC‐ASL was significantly smaller than PC‐DCE, but this was driven by a single‐DCE outlier (P = 0.31, after removing outlier). The difference in split‐RBF was comparatively small. In HVs, mean RE (±95% CI; mL/min/1.73 m2) was significantly smaller for PC (79 ± 41) than for ASL (241 ± 85). Conclusions: ASL, DCE, and PC RBF show poor agreement in individual subjects but agree well on average. Triangulation with PC suggests that the accuracy of ASL and DCE is comparable. Evidence Level 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level‐dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply. Purpose To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD. Study Type: Prospective. Animal Model: Thirty‐five New Zealand White rabbits were divided into control group (n = 5) and alloxan‐induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15). Field Strength/Sequence: 3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin‐echo (ASE). Assessment The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS). Statistical Tests: Analysis of variance, independent‐sample t‐test, and paired‐sample t‐test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant. Results: All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively). Data Conclusion: BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change. Level of Evidence: 2 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Background: Although perfusion imaging plays a key role in the management of steno‐occlusive diseases, the clinical usefulness of arterial spin labeling (ASL) is limited by technical issues. Purpose To examine the effect of arterial transit time (ATT) prolongation on cerebral blood flow (CBF) measurement accuracy and identify the best CBF measurement protocol for steno‐occlusive diseases. Study Type: Prospective. Population: Moyamoya (n = 10) and atherosclerotic diseases (n = 8). Field Strength/Sequence: A 3.0T/3DT1‐weighted and ASL. Assessment Hadamard‐encoded multidelay ASL scans with/without vessel suppression (VS) and single‐delay ASL scans with long‐label duration (LD) and long postlabeling delay (PLD), referred to as long‐label long‐delay (LLLD), were acquired. CBF measurement accuracy and its ATT dependency, measured as the correlation between the relative CBF measurement difference (ASL—single‐photon emission computed tomography [SPECT]) and ATT, were compared among 1) Combo (incorporating multidelay and LLLD data based on ATT), 2) standard (LD/PLD = 1333/2333 msec), and 3) LLLD (LD/PLD = 4000/4000 msec) protocols, using whole‐brain voxel‐wise correlation with reference standard SPECT CBF. The effect of VS on CBF measurement accuracy was also assessed. Statistical Tests: Pearson's correlation coefficient, repeated‐measures analysis of variance, t‐test. P< 0.05 was considered significant. Results: Pearson's correlation coefficients between ASL and SPECT CBF measurements were as follows: Combo = 0.55 ± 0.09; standard = 0.52 ± 0.12; LLLD = 0.41 ± 0.10. CBF measurement was least accurate in LLLD and most accurate in Combo. VS significantly improved overall CBF measurement accuracy in the standard protocol and in moyamoya patients for the Combo. ATT dependency analysis revealed that, compared with Combo, the standard and LLLD protocols showed significantly lower and negative and significantly higher and positive correlations, respectively (standard = −0.12 ± 0.04, Combo = −0.04 ± 0.03, LLLD = 0.17 ± 0.03). Data Conclusion: By using ATT‐corrected CBF derived from LD/PLD = 1333/2333 msec as a base and by compensating underestimation in delayed regions using multidelay scans, the ATT‐based Combo strategy improves CBF measurement accuracy compared with single‐delay protocols in severe steno‐occlusive diseases. Evidence Level 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

PurposeTo investigate the hemodynamic changes of normal-appearing white matter (NAWM) in hypertension using the 3D pseudocontinuous arterial spin labeling (pCASL) technique.Materials and methodsSeventy-three subjects, including a patient group (n = 41; 30 males; age = 47.7 ± 8.3 years; test-time blood pressure [BP] = 155 ± 23/98 ± 11 mmHg) and an age-matched control group (n = 32; 14 males; age = 46 ± 8.3 years; test-time BP = 117 ± 8/76 ± 10 mmHg), were recruited and scanned on a 3.0T magnetic resonance imaging (MRI) system using routine MRI sequences and 3D pCASL sequence. The routine MRI sequences were used to further define the NAWM. The cerebral blood flow (CBF) values in various regions of interest (ROIs) were extracted. One-way analysis of variance (ANOVA) and unpaired t-test were performed to evaluate the significance of the intergroup difference in CBF modifications.ResultsCompared to healthy volunteers, CBF values in global gray matter (GM) and various NAWM regions were found to be lower (P  0.05). Furthermore, compared to the control group, mild hypertension showed significantly reduced CBF in various ROIs (P  0.05), while moderate hypertension showed reduced CBF in all ROIs (P

Background: Dynamic contrast‐enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium‐based contrast agent, screening with DCE‐MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast‐enhanced alternative to DCE is desirable. Purpose: To investigate whether velocity selective arterial spin labeling (VS‐ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue. Study Type: Prospective. Population: Eight breast cancer patients. Field Strength/Sequence: A 3 T; VS‐ASL with multislice single‐shot gradient‐echo echo‐planar‐imaging readout. Assessment: VS‐ASL scans were independently assessed by three radiologists, with 3–25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3‐point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI‐RADS lexicon), as assessed in the standard clinical exam. Statistical Tests: Intra‐class correlation coefficient (ICC) for interobserver agreement. Results: The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score. Data Conclusion: We have demonstrated the technical feasibility of bilateral whole‐breast perfusion imaging using VS‐ASL in breast cancer patients. Evidence Level: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background: Disruption of brain oxygen delivery and consumption after hypoxic–ischemic injury contributes to neonatal mortality and neurological impairment. Measuring cerebral hemodynamic parameters, including cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2), is clinically important. Purpose: Phase‐contrast (PC), velocity‐selective arterial spin labeling (VSASL), and T2‐relaxation‐under‐phase‐contrast (TRUPC) are magnetic resonance imaging (MRI) techniques that have shown promising results in assessing cerebral hemodynamics in humans. We aimed to test their feasibility in quantifying CBF, OEF, and CMRO2 in piglets. Study Type: Prospective. Animal Model: Ten neonatal piglets subacutely recovered from global hypoxia‐ischemia (N = 2), excitotoxic brain injury (N = 6), or sham procedure (N = 2). Field Strength/Sequence: VSASL, TRUPC, and PC MRI acquired at 3.0 T. Assessment: Regional CBF was measured by VSASL. Global CBF was quantified by both PC and VSASL. TRUPC assessed OEF at the superior sagittal sinus (SSS) and internal cerebral veins (ICVs). CMRO2 was calculated from global CBF and SSS‐derived OEF. End‐tidal carbon dioxide (EtCO2) levels of the piglets were also measured. Brain damage was assessed in tissue sections postmortem by counting damaged neurons. Statistical Tests: Spearman correlations were performed to evaluate associations among CBF (by PC or VSASL), OEF, CMRO2, EtCO2, and the pathological neuron counts. Paired t‐test was used to compare OEF at SSS with OEF at ICV. Results: Global CBF was 32.1 ± 14.9 mL/100 g/minute and 30.9 ± 8.3 mL/100 g/minute for PC and VSASL, respectively, showing a significant correlation (r = 0.82, P < 0.05). OEF was 54.9 ± 8.8% at SSS and 46.1 ± 5.6% at ICV, showing a significant difference (P < 0.05). Global CMRO2 was 79.1 ± 26.2 μmol/100 g/minute and 77.2 ± 12.2 μmol/100 g/minute using PC and VSASL‐derived CBF, respectively. EtCO2 correlated positively with PC‐based CBF (r = 0.81, P < 0.05) but negatively with OEF at SSS (r = −0.84, P < 0.05). Relative CBF of subcortical brain regions and OEF at ICV did not significantly correlate, respectively, with the ratios of degenerating‐to‐total neurons (P = 0.30, P = 0.10). Data Conclusion: Non‐contrast MRI can quantify cerebral hemodynamic parameters in normal and brain‐injured neonatal piglets. Level of Evidence: 1 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background: A noninvasive method for evaluating renal blood flow (RBF) in patients with chronic kidney disease (CKD) may have clinical value in disease staging, management, and prognostication. Purpose: To evaluate effectiveness of three‐dimensional pseudocontinuous arterial spin labeling (pCASL) and pulsed arterial spin labeling (PASL) in assessment of cortex and outer medulla (cortex/OM) RBF in CKD patients and healthy volunteers (HVs). Study Type: Prospective, in a single institution. Subjects: A total of 48 CKD patients (stage 1, 2, 3, and 4–5: N = 11, 12, 13, and 12, respectively) and 18 HVs Field Strength/Sequence: 3 T, pCASL, and PASL with a three‐dimensional hybrid gradient echo/spin echo sequence. Assessment: Quality of RBF images derived from pCASL and PASL were evaluated and RBF in cortex/OM measured. Clinical and laboratory data were recorded. Statistical Tests: Image quality differences between pCASL and PASL were evaluated with Wilcoxon signed‐rank test. For both methods, analysis of variance, followed by Fisher's LSD‐t test, was used to determine whether RBF differed between CKD stages and HVs. Pearson correlation coefficients were calculated to assess strength of relationships between cortex/OM RBF and data from clinical and laboratory tests. Results: Image quality differences were significantly higher in pCASL than PASL in both patients and HVs (both P < 0.05). For pCASL, cortex/OM RBF of patients were significantly lower than those of HVs (P < 0.05). Cortex/OM RBF were higher in S1 and S2 patients than those in S3 and S4–5 (P < 0.05). For PASL, only RBF in cortex of S1 and S2 patients were significantly higher than those of S4–5 (P < 0.05). Good correlations between pCASL RBF and estimated glomerular filtration (eGFR) were found in cortex/OM of patients (rho = 0.796 and 0.798, respectively, both P < 0.05), higher than those between PASL RBF and eGFR (rho = 0.430 and 0.374, respectively, both P < 0.05). Data Conclusion: Three‐dimensional pCASL may potentially be a noninvasive technique to assess renal perfusion in CKD patients in different stages. Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Flow related artifacts in continuous arterial spin labeling (cASL) zero‐echo‐time (ZTE) magnetic resonance angiography (MRA) could influence the vasculature visualization. Purpose: To investigate the clinical feasibility for the intracranial artery diseases assessment by utilizing hybrid ASL‐ZTE‐MRA (hASL‐ZTE‐MRA). Study Type: Prospective, technical development. Population: Sixty‐seven subjects with known/suspected cerebrovascular diseases. Field Strength/Sequence: Gradient echo based cASL‐/hASL‐ ZTE‐MRA at 3.0 T. Assessment: Subjective/objective evaluation for sound‐levels. Image quality (IQ), signal‐to‐noise ratio (SNR), and contrast‐to‐noise ratio (CNR) were analyzed within artery segments. Stenotic grading, aneurysm measurement, and signal intensity of lesions were further analyzed. Statistical Tests: Kolmogorov–Smirnov test for data normality check. Between two MRAs: Wilcoxon signed‐rank test for sound experience/IQ ratings analysis; Paired t test for SNR/CNR comparison. One‐way analysis of variance for sound intensity comparison. For stenosis grading/aneurysm measurement: Kendall's W test/intraclass correlation coefficient (ICC) for interobserver agreement test within each modality, weighted kappa statistics/ICC for intermodality agreement test between each MRA and computed tomography angiography. Results: Sound‐level perception/intensity was similar (P = 0.86, P = 0.55) between MRAs. The mean IQ score for hASL‐ZTE‐MRA was on diagnostic scale and slightly higher (P < 0.05) than that of cASL‐ZTE‐MRA. hASL‐ZTE‐MRA provided higher (P < 0.05) SNR/CNR than that of cASL‐ZTE‐MRA. Signal uniformity was improved on hASL‐ZTE‐MRA, particularly among the anterior circulation (P < 0.05). Comparing to cASL‐ZTE‐MRA, on hASL‐ZTE‐MRA, stenotic lesions were accurately assessed; flow in the stent or aneurysm remnant was better depicted (P < 0.05); AVM nidus was preferred with increased SNR (P < 0.05). No significant differences for the aneurysm measurement were found between MRAs (P = 0.95), in addition to the slightly higher SNR (P < 0.05) on hASL‐ZTE‐MRA. Data Conclusion: Comparing to cASL‐ZTE‐MRA, hASL‐ZTE‐MRA is robust and feasible for the evaluation of intracranial artery diseases with diagnostic IQ, improved vessel contrast, and better signal heterogeneity. Level of Evidence: 2 Technical Efficacy: 2 [ABSTRACT FROM AUTHOR]

Background: Unilateral middle cerebral artery (MCA) stenosis, as an independent risk factor for stroke, requires an intervention operation for vessel recanalization. Accurate perfusion measurement is thus essential after the operation.Purpose: To explore the feasibility of three-dimensional (3D) pseudo-continuous territorial arterial-spin-labeling (tASL) in evaluating MCA recanalization.Study Type: Prospective and longitudinal.Subjects: Forty-seven patients with unilateral MCA stenosis or occlusion.Field Strength/sequence: A 3.0 T, 3D time-of-flight fast-field-echo magnetic resonance (MR) angiography sequence, spin-echo echo-planar diffusion-weighted imaging sequence, 3D fast-spin-echo pseudo-continuous ASL (pcASL) and tASL sequences.Assessment: All patients underwent MR examination before and after MCA recanalization and scored using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admission and discharge. An mRS score <2 was defined as a good prognosis. 3D-pcASL and tASL cerebral blood flow (CBF) maps were obtained, and the corresponding Alberta Stroke Program Early CT Score (ASPECTS)-based scores were evaluated.Statistical Tests: The Kolmogorov-Smirnov test, intra-class correlation coefficient, paired t-test, receiver operating characteristic (ROC) curve, and multivariable logistic regression analysis.Results: After recanalization, tASL derived absolute CBFs between the affected and contralateral sides were significantly higher than before the operation (mean: 34.3 ± 8.5 mL/100 g/min vs. 40.6 ± 9.2 mL/100 g/min, 42.6 ± 9.8 mL/100 g/min vs. 43.5 ± 9.9 mL/100 g/min, both P < 0.05). In ROC analysis, tASL provided good prognosis (area under ROC curve [AUC] = 0.829; 95% CI: 0.651-1.000, P < 0.05), while pcASL had lower prognostic value (AUC = 0.760; 95% CI: 0.574-0.946, P < 0.05). The NIHSS score before recanalization, pcASL, and tASL-based ASPECTS scores were significantly associated with good clinical outcome (P < 0.05). Multivariable analysis revealed that ASPECTS-based scores of pcASL and tASL before and after surgery were independent predictors of good clinical outcome (all P < 0.05). DATA CONCLUSION: tASL can determine hypoperfusion in the responsible vascular perfusion area and predict clinical outcome.Evidence Level: 4 TECHNICAL EFFICACY: Stage 2. [ABSTRACT FROM AUTHOR]

Background: Differentiating nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoma (NPL) is useful for deciding the appropriate treatment. However, the diagnostic accuracy of current imaging methods is low. Purpose: To explore the feasibility of arterial spin labeling (ASL) perfusion imaging in the qualitative and quantitative differentiation between NPC and NPL to improve the diagnosis of malignancies in the nasopharynx. Study Type: Retrospective. Population: Ninety seven patients: NPC (65 cases) and NPL (32 cases), histologically confirmed. Field Strength/Sequence: 3T/3D fast spin echo pseudo‐continuous ASL imaging with spiral readout scheme, 3D inverse recovery–fast spoiled gradient recalled echo brain volume (BRAVO) imaging. Assessment: Cerebral blood flow (CBF) images from ASL perfusion imaging were assessed by three radiologists. Each tumor was visually scored based on CBF images. Intratumoral CBF and intramuscular CBF values were obtained from intratumoral and lateral pterygoid muscle areas, respectively. Through dividing intratumoral CBF by intramuscular CBF, normalized CBF (nCBF) was further calculated. Statistical Tests: Fleiss's kappa and intraclass correlation coefficients (ICCs) were used to assess interobserver agreement among the three readers. The Mann–Whitney U‐test was used to compare visual scoring, and an unpaired t‐test was performed to compare CBF value between the NPC and NPL groups. The area under the curve (AUC) value was used to quantify the diagnostic ability of each parameter. Results: Good interobserver agreements were validated by high Fleiss's kappa and ICC values (all >0.80). NPCs showed significantly higher visual scores than NPLs (P < 0.05). Both intratumoral CBF and nCBF in NPC were significantly higher than those in NPL (both P < 0.05). Intratumoral CBF showed the highest AUC of 0.861 (P < 0.05) in differentiating NPC (n = 65) from NPL (n = 32), while the AUCs of nCBF and visual scoring were 0.847 and 0.753, respectively. Data Conclusion: For the diagnosis of distinguishing NPC from NPL, ASL perfusion imaging demonstrated high diagnostic efficiency. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

PurposeTo investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient-echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively.Materials and methodsEach sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment (MCI), and one participant with Alzheimer's disease (AD). Eight of these subjects also underwent H2 (15) O positron emission tomography (PET) scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV).ResultsThe ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant.ConclusionThe 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects.

Background: Myocardial perfusion is evaluated in first‐pass MRI using a gadolinium‐based contrast agent, which limits its repeatability and restricts its use in patients with abnormal kidney function. Arterial spin labeling (ASL) is a promising technique for measuring myocardial perfusion without contrast injection. The ratio of stress to rest perfusion, termed myocardial perfusion reserve (MPR), is an indicator of the severity of stenosis in patients with coronary artery disease (CAD). Purpose: To quantify perfusion increases with pharmacological vasodilation, explore MPR differences between segments with and without perfusion defects, and examine the correlations between quantitative ASL and semiquantitative first‐pass measurements. Study Type: Prospective. Subjects: Sixteen patients with suspected CAD: 10 classified as "healthy," having normal perfusion on first‐pass and no enhancement on late gadolinium enhancement (LGE), and six as "nonhealthy," having hypoperfused segments including ischemic and infarcted. Field Strength/Sequence: Flow‐sensitive alternating inversion recovery (FAIR) rest–stress cardiac ASL with balanced steady‐state free precession (bSSFP), rest–stress first‐pass imaging using gradient‐echo and LGE using a phase‐sensitive inversion‐recovery bSSFP at 1.5T. Assessment: For healthy subjects, rest–stress perfusion data were compared in global, coronary artery territory, and segment regions of interest (ROIs). A segmental MPR comparison was performed between normal segments from healthy subjects and abnormal segments from nonhealthy subjects. Correlations between ASL and first‐pass parameters were explored. Statistical Tests: Wilcoxon‐signed‐rank test, nonparametric factorial analysis of variance (ANOVA), and Pearson's/Spearman's correlations. Results: Perfusion increases were significant globally (P = 0.005), per coronary artery territory (P = 0.015), and per segment (P = 0.03 for all segments in ASL and first‐pass, except anteroseptal in ASL P = 0.04). MPR differences between normal and abnormal segments were significant (P = 0.0028: ASL, P = 0.033: first‐pass). ASL and first‐pass measurements were correlated (MPR: r = 0.64, P = 0.008 and perfusion: rho = 0.47, P = 0.007). Data Conclusion: This study demonstrates the feasibility of ASL to detect hyperemia, the potential to differentiate segments with and without perfusion defects, and significant correlations between ASL and semiquantitative first‐pass. Level of Evidence: 2 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) is a useful tool for measuring cerebral blood flow (CBF). However, due to the low signal-to-noise ratio (SNR) of the technique, multiple repetitions are required, which results in prolonged scan times and increased susceptibility to artifacts.Purpose: To develop a deep-learning-based algorithm for simultaneous denoising and suppression of transient artifacts in ASL images.Study Type: Retrospective.Subjects: 131 pediatric neuro-oncology patients for model training and 11 healthy adult subjects for model evaluation.Field Strength/sequence: 3T / pseudo-continuous and pulsed ASL with 3D gradient-and-spin-echo readout.Assessment: A denoising autoencoder (DAE) model was designed with stacked encoding/decoding convolutional layers. Reference standard images were generated by averaging 10 pairwise ASL subtraction images. The model was trained to produce perfusion images of a similar quality using a single subtraction image. Performance was compared against Gaussian and non-local means (NLM) filters. Evaluation metrics included SNR, peak SNR (PSNR), and structural similarity index (SSIM) of the CBF images, compared to the reference standard.Statistical Tests: One-way analysis of variance (ANOVA) tests for group comparisons.Results: The DAE model was the only model to produce a significant increase in SNR compared to the raw images (P < 0.05), providing an average SNR gain of 62%. The DAE model was also effective at suppressing transient artifacts, and was the only model to show a significant improvement in accuracy in the generated CBF images, as assessed using PSNR values (P < 0.05). In addition, using data from multiple inflow time acquisitions, the DAE images produced the best fit to the Buxton kinetic model, offering a 75% reduction in the fitting error compared to the raw images.Data Conclusion: Deep-learning-based algorithms provide superior accuracy when denoising ASL images, due to their ability to simultaneously increase SNR and suppress artifactual signals in raw ASL images.Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 1. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and most malignant primary brain tumor. Despite aggressive multimodal treatment, its prognosis remains poor. Even with continuous developments in MRI, which has provided us with newer insights into the diagnosis and understanding of tumor biology, response assessment in the posttherapy setting remains challenging. We believe that the integration of additional information from advanced neuroimaging techniques can further improve the diagnostic accuracy of conventional MRI. In this article, we review the utility of advanced neuroimaging techniques such as diffusion-weighted imaging, diffusion tensor imaging, perfusion-weighted imaging, proton magnetic resonance spectroscopy, and chemical exchange saturation transfer in characterizing and evaluating treatment response in patients with glioblastoma. We will also discuss the existing challenges and limitations of using these techniques in clinical settings and possible solutions to avoiding pitfalls in study design, data acquisition, and analysis for future studies. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:978-997. [ABSTRACT FROM AUTHOR]

Renal perfusion can be quantitatively assessed by multiple magnetic resonance imaging (MRI) methods, including dynamic contrast enhanced (DCE), arterial spin labeling (ASL), and diffusion-weighted imaging with intravoxel incoherent motion (IVIM) analysis. In this review we summarize the advances in the field of renal-perfusion MRI over the past 5 years. The review starts with a brief introduction of relevant MRI methods, followed by a discussion of recent technical developments. In the main section of the review, we examine the clinical and preclinical applications for three disease populations: chronic kidney disease, renal transplant, and renal tumors. The DCE method has been routinely used for assessing renal tumors but not other renal diseases. As a noncontrast alternative, ASL was extensively explored in both preclinical and clinical applications and showed much promise. Protocol standardization for the methods is desperately needed, and then large-scale clinical trials for the methods can be initiated prior to their broad clinical use. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:369-379. [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) can be confounded by varying arterial transit times (ATT) across the brain and with disease. Hadamard encoding schemes can be applied to 3D pseudocontinuous ASL (pCASL) to acquire ASL data with multiple postlabeling delays (PLDs) to estimate ATT and then correct cerebral blood flow (CBF).Purpose: To assess the longitudinal reproducibility of 3D pCASL with Hadamard-encoded multiple PLDs.Study Type: Prospective, longitudinal.Population: Fifty-two healthy, right-handed male subjects who underwent imaging at four timepoints over 45 days.Field Strength/sequence: A Hadamard-encoded 3D pCASL sequence was acquired at 3.0T with seven PLDs from 1.0-3.7 sec.Assessment: ATT and corrected CBF (cCBF) were computed. Conventional uncorrected CBF (unCBF) was also estimated. Within- and between-subject coefficient of variation (wCV and bCV, respectively) and intraclass correlation coefficient (ICC) were evaluated across four time intervals: 7, 14, 30, and 45 days, in gray matter and 17 independent regions of interest (ROIs). A power analysis was also conducted.Statistical Tests: A repeated-measures analysis of variance (ANOVA) was used to compare ATT, cCBF, and unCBF across the four scan sessions. A paired two-sample t-test was used to compare cCBF and unCBF. Pearson's correlation was used to examine the relationship between the cCBF and unCBF difference and ATT. Power calculations were completed using both the cCBF and unCBF variances.Results: ATT showed the lowest wCV and bCV (3.3-4.4% and 6.0-6.3%, respectively) compared to both cCBF (10.5-11.7% and 20.6-22.2%, respectively) and unCBF (12.0-13.6% and 22.7-23.7%, respectively). wCV and bCV were lower for cCBF vs. unCBF. A significant difference between cCBF and unCBF was found in most regions (P = 5.5 × 10-5 -3.8 × 10-4 in gray matter) that was highly correlated with ATT (R2 = 0.79-0.86). A power analysis yielded acceptable power at feasible sample sizes using cCBF.Data Conclusion: ATT and ATT-corrected CBF were longitudinally stable, indicating that ATT and CBF changes can be reliably evaluated with Hadamard-encoded 3D pCASL with multiple PLDs.Level Of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1846-1853. [ABSTRACT FROM AUTHOR]

Background: Stroke risk stratification in patients with symptomatic intracranial atherosclerotic arterial disease (ICAD) remains an important clinical objective owing to the high 14-19% recurrent stroke rate in these patients on standard-of-care medical management. There thus remains a need for hemodynamic markers that may allow for the selection of personalized therapies for high-risk symptomatic patients.Purpose: To determine if shifting of cerebral blood flow (CBF) territories in response to changes in cerebral perfusion pressure (CPP) may provide a marker for stroke risk in ICAD patients.Study Type: Prospective.Population: Twenty ICAD patients who experienced a stroke within 45 days of study enrollment and 10 healthy controls.Sequence: 3.0T MRI including anatomical imaging (T1 -weighted, T2 -weighted/FLAIR), 3D MR angiography, and normocapnic and hypercapnic vessel-encoded CBF-weighted arterial spin labeling.Assessment: Patients were scanned within 45 days of overt stroke and monitored (duration = 13.2 ± 4.4 months) for the endpoint of non-cardioembolic stroke or transient ischemic attack. Flow territory shifting (shifting index) was calculated from the first scan by determining whether a voxel shifted from its primary arterial source from normocapnia to hypercapnia.Statistical Tests: A Mann-Whitney U-test (significance: P < 0.05) was performed to determine whether patients meeting the endpoint had greater shifting indices relative to controls or patients not meeting the endpoint.Results: Shifting indices (mean ± standard error) were significantly higher in patients meeting endpoint criteria relative to controls (P = 0.0057; adjusted P = 0.036) and patients not meeting endpoint criteria (P = 0.0047; adjusted P = 0.036).Data Conclusion: Flow territory shifting may provide a marker of recurrent stroke risk in symptomatic ICAD patients on standard-of-care medical management therapies.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1441-1451. [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling with 3D acquisition requires determining a single postlabeling delay (PLD) value. PLD affects the signal-to-noise ratio (SNR) per unit time as well as quantitative cerebral blood flow (CBF) values due to its bearing on the presence of a vascular signal.Purpose: To search for an optimal PLD for pseudocontinuous arterial spin labeling (pCASL) using patient-specific carotid artery blood velocity measurements.Study Type: Prospective.Subjects: A control group of 11 volunteers with no known pathology. Corroboration was through a separate group of six volunteers and a noncontrol group of five sickle cell disease (SCD) patients.Field Strength/sequence: Pseudocontinuous arterial spin labeling with 3D nonsegmented echo planar imaging acquisition at 3T.Assessment: A perfusion-based measure was determined over a range of PLDs for each of 11 volunteers. A third-order polynomial was used to find the optimal PLD where the defined measure was maximum. This was plotted against the corresponding carotid artery velocity to determine a relationship between the perfusion measure and velocity. Corroboration was done using a group of six volunteers and a noncontrol group of five patients with SCD. PLD was determined from the carotid artery velocity and derived relationship and compared with optimal PLD obtained from measured perfusion over a range of PLD values. Error between the perfusion measure at predicted and measured optimal PLD was determined.Statistical Tests: Chi-squared goodness of fit; Pearson correlation; Bland-Altman.Results: Carotid artery velocity was 63.8 ± 6.6 cm/s (53.1 ≤ v ≤ 72.3 cm/s) while optimal PLD was 1374 ± 226.5 msec (1102 ≤ PLD ≤ 1787 msec) across the 11 volunteers. PLD as a function of carotid velocity was determined to be PLD = -31.94. v + 3410 msec (Pearson correlation -0.93). In six volunteers, mean error between the perfusion measure at predicted and measured optimal PLD was 1.35%. Pearson correlation between the perfusion measure at the predicted PLD and the measure obtained experimentally was r = 0.96 (P < 0.001). Bland-Altman revealed a slight bias of 1.3%. For the test case of five SCD patients, the mean error was 1.3%.Data Conclusion: Carotid artery velocity was used to determine optimal PLD for pCASL with 3D acquisition. The derived relationship was used to predict optimal PLD and the associated perfusion measure, which was found to be accurate when compared with its measured counterpart.Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:951-960. [ABSTRACT FROM AUTHOR]

Background: There is a need for an imaging-based tool for measuring vascular endothelial growth factor (VEGF) expression and overall survival (OS) in patients with glioma.Purpose: To assess the correlation between cerebral blood flow (CBF), measured by 3D pseudo-continuous arterial spin-labeling (3D-ASL), and VEGF expression in gliomas on the basis of coregistered localized biopsy, and investigate whether CBF correlated with survival month (SM) in glioma patients.Study Type: Prospective cohort.Subjects: Thirty-seven patients with gliomas from whom 63 biopsy specimens were obtained.Sequence: 3D-ASL acquired with a 3.0T MR unit.Assessment: Biopsy specimens were grouped as high-grade (HGG) or low-grade glioma (LGG). CBF measurements were spatially matched with VEGF expression by coregistered localized biopsies, and the CBF value was correlated with quantitative VEGF expression for each specimen. Patients' survival information was derived and connected with CBF.Statistical Tests: Patients' OS was analyzed by Kaplan-Meier and Cox-regression methods. VEGF expression and CBF were compared in both LGG and HGG. The Spearman rank correlation was calculated for CBF and VEGF expression, SM. Significance level, P < 0.05.Results: CBF-derived 3D-ASL positively correlated significantly with VEGF expression in both LGG (31 specimens) and HGG (32 specimens), r = 0.604 (P < 0.001) and r = 0.665 (P < 0.001), respectively. LGG and HGG together gave a correlation coefficient r = 0.728 (P < 0.001). Median survival for LGG and HGG patients was 34.19 and 17.17 months, respectively (P = 0.037); CBF value negatively correlated significantly with SM with r = -0.714 (P < 0.001) regardless of glioma grade. CBF was an independent risk factor for OS with HR = 1.027 (P = 0.044), 1.028 (P = 0.010) for univariate/multivariate regression analysis.Data Conclusion: CBF determined by 3D-ASL correlates with VEGF expression in glioma and is an independent risk factor for OS in these patients.Level Of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:209-220. [ABSTRACT FROM AUTHOR]

Background: Quantifying blood perfusion in ocular tissues is challenging, partly because the majority of the blood is carried by the choroid, which is difficult to visualize because it is located between the retina and sclera.Purpose/hypothesis: To evaluate the intra- and interday repeatability of MRI measures of chorio-retinal blood perfusion.Study Type: Prospective, cross-sectional, observational study.Population: Twenty young healthy adults (six male, age: 25 ± 5 years) scanned twice within a single session repeated at the same time of day on 2 days.Field Strength/sequence: Arterial spin labeling (ASL) MRI at 3.0T using pseudocontinuous ASL (PCASL) labeling scheme and a 3D turbo-gradient-spin-echo (TGSE) acquisition, including axial T2 -weighted structural images using a 2D turbo-spin-echo (TSE) sequence.Assessments: Region-of-interest analysis for assessment of chorio-retinal blood perfusion.Statistical Tests: Intra- and interday repeatability of measures analyzed using intraclass correlation coefficients (ICC), Pearson's correlation analysis, paired t-tests, and Bland-Altman plots.Results: The mean chorio-retinal perfusion was 77.86 (standard deviation [SD] = 29.80) ml/100ml/min. Perfusion measurements correlated strongly within a single session (r = 0.95, 95% confidence interval [CI] [0.880-0.980], P < 0.001) and between the two sessions based on a single run (r = 0.80 [0.582-0.913], P < 0.001), and two runs (r = 0.80 [0.479-0.918], P < 0.001). There were mean differences of 2.69 [16.85 to -22.23] ml/100ml/min for intraday measures, -7.44 [27.45 to -42.32] ml/100ml/min for single-run interday measures, and 5.73 [28.71 to -40.17] ml/100ml/min for two-run interday measures, but none were significant (all P > 0.05).Data Conclusion: Quantitative ASL-MRI measurements of chorio-retinal blood perfusion showed high intra- and interday repeatability. The ASL-MRI technique provides reliable measures of chorio-retinal perfusion in vivo.Level Of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:966-974. [ABSTRACT FROM AUTHOR]

Background: Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies.Purpose/hypothesis: To investigate the consistency of repeated functional MRI measurements in healthy subjects.Study Type: Prospective, longitudinal study.Subjects: Seventeen healthy subjects were examined on two different occasions, 18 months apart.Field Strength/sequence: Multiple gradient-recalled-echo, 2D navigator-gated flow-sensitive alternating inversion recovery True-FISP and spin-echo planar diffusion-weighted sequences were used on a 3T scanner. Images were acquired on two different scanner configurations.Assessment: Blood oxygenation level-dependent (BOLD) R2*, arterial spin labeling (ASL) perfusion-derived blood flow (BF) and apparent diffusion coefficient (ADC) maps were analyzed using a custom image processing toolbox. Regions of interest (ROIs) were placed on renal cortex, medulla, and whole kidney. Multiple researchers were involved in defining the ROIs.Statistical Tests: Intra- and intersubject coefficients of variation (CV) and Bland-Altman plots were used to measure consistency and evaluate bias in the measurements. A nonparametric Wilcoxon test was used to compare differences between two timepoints.Results: The intrasubject CV for R2* and ADC were 6.8% and 5.3% with small (-3.8 and 5.3%) bias, respectively, comparing baseline and 18-month data. Intrasubject CV for renal cortex BF was higher (18.7%) compared to R2* and ADC, but comparable to prior literature values over shorter durations. It also exhibited a larger bias (-15.4%) between two timepoints and significantly lower values (P = 0.022) at 18-month data.Data Conclusion: All three MRI parameters over 18 months, even with a scanner upgrade and involving multiple observers, showed good consistency. These results are useful for the interpretation of longitudinal data and support the use of these methods to monitor progression in patients with CKD.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:514-521. [ABSTRACT FROM AUTHOR]

Background: With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment.Purpose/hypothesis: To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up.Study Type: Prospective longitudinal study with a 4-year time interval.Population: 309 healthy subjects aged 20-89 years old.Field Strength/sequence: 3T pseudo-continuous-arterial-spin-labeling MRI.Assessment: CBF at baseline and cognitive assessment at both baseline and follow-up.Statistical Tests: Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates.Results: Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ≥54 years, β = 0.221, P = 0.004), but not in younger or entire sample (β = 0.018, P = 0.867 and β = 0.089, P = 0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (β = 0.244 P = 0.001), episodic memory (β = 0.294, P = 0.001), and reasoning (β = 0.186, P = 0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition.Data Conclusion: In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function.Level Of Evidence: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458. [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) based-noncontrast-enhanced 4D MR angiography (NCE 4D MRA) shows potential in characterizing cerebrovascular hemodynamics in cerebrovascular disorders. Ultrahigh-field theoretically benefits ASL signal with increased inherent signal-to-noise ratio (SNR) and prolonged blood T1 , which may provide improved delineation of vasculature in 4D MRA.Purpose: To investigate the feasibility of NCE 4D MRA using 3D Cartesian trajectory and stack-of-stars (SOS) golden angle radial trajectory at 7T.Study Type: A prospective study.Subjects: Six normal volunteers and eight patients with arteriovenous malformation (AVM).Field Strength/sequence: NCE 4D MRA with Cartesian and radial trajectories were performed at 3T and 7T.Assessment: Subjective image quality of 4D MRA was evaluated using a 4-point scale by two experienced neuroradiologists. The characterization of AVM components with 4D MRA and DSA was also graded using the Spetzler-Martin grading scale.Statistical Tests: Cohen's kappa coefficient was calculated to evaluate the agreement between two readers within each 4D MRA technique (Cartesian and Radial). A Wilcoxon signed-rank test was performed to compare the subjective image quality scores of 4D MRA between Cartesian and radial trajectories, and between 7T and 3T, respectively.Results: Good-to-excellent image quality was achieved in 4D MRA with both Cartesian (3.83 ± 0.41) and radial (3.42 ± 0.49) acquisitions in healthy volunteers at 7T. However, markedly reduced scan time was needed with radial acquisition. 4D MRA at 7T (3.31 ± 0.59) shows better delineation of AVM lesion features, especially the vein drainage, compared with that of 3T (2.83 ± 0.75), although no statistical significance was achieved (P = 0.180).Data Conclusion: The feasibility of ASL based 4D MRA at 7T with Cartesian and SOS golden angle radial acquisition was demonstrated. The clinical evaluation of 4D MRA in AVMs between 3T and 7T suggested 7T 4D MRA images acquired with radial acquisition demonstrate excellent delineation of AVM features, especially the draining veins.Level Of Evidence: 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017. [ABSTRACT FROM AUTHOR]

Background: Previously, a theoretical model based on microvascular physiology was established to facilitate the interpretation of calf perfusion dynamics recorded by arterial spin labeling (ASL).Purpose: To investigate the clinical relevance of novel perfusion indices by comparing them to the symptoms, response to revascularization, and short-term functional outcome in patients with peripheral arterial disease (PAD).Study Type: Prospective cohort study.Population: Nineteen patients with PAD.Field Strength/sequence: Pulsed ASL at 3T.Assessment: The mid-calf reactive hyperemia induced by 2 minutes of arterial occlusion was recorded in PAD patients. The perfusion responses were characterized by the peak, time-to-peak, and physiological model-derived indices including the baseline perfusion fr , arterial resistance Ra , and compliance Ca , and sensitivity gATP and response time τATP of downstream microvasculature to metabolic stress. These indices were compared to the disease severity and outcome within 6 months after revascularization assessed by self-reported symptoms and the ankle-brachial index. Disease severity was categorized as asymptomatic, claudication, or critical limb ischemia. The outcome was categorized as symptom resolved or limited improvement.Statistical Tests: Severity and outcome groups were compared using Mann-Whitney and Kruskal-Wallis tests with Holm-Sidak adjustments.Results: The peak perfusion decreased and model arterial resistance increased progressively with increasing severity of limb ischemia (P = 0.0402 and 0.0413, respectively). Eleven patients had a successful endovascular procedure, including six patients who had symptoms resolved, four patients who had remaining leg pain, and one patient lost to follow-up. The subjects with limited improvement had significantly lower preintervention microvascular sensitivity gATP than those with symptoms resolved (8.72 ± 1.46 vs. 4.93 ± 0.91, P = 0.0466).Data Conclusion: ASL reactive hyperemia reflects multiple aspects of the pathophysiology. Measures of macrovascular arterial disease are related to the manifested symptom severity, whereas preintervention gATP associated with microvascular dysfunction is related to prognosis following revascularization.Level Of Evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1578-1588. [ABSTRACT FROM AUTHOR]

Purpose: To compare registration strategies to align arterial spin labeling (ASL) with 3D T1-weighted (T1w) images, with the goal of reducing the between-subject variability of cerebral blood flow (CBF) images.Materials and Methods: Multi-center 3T ASL data were collected at eight sites with four different sequences in the multi-center GENetic Frontotemporal dementia Initiative (GENFI) study. In a total of 48 healthy controls, we compared the following image registration options: (I) which images to use for registration (perfusion-weighted images [PWI] to the segmented gray matter (GM) probability map (pGM) (CBF-pGM) or M0 to T1w (M0-T1w); (II) which transformation to use (rigid-body or non-rigid); and (III) whether to mask or not (no masking, M0-based FMRIB software library Brain Extraction Tool [BET] masking). In addition to visual comparison, we quantified image similarity using the Pearson correlation coefficient (CC), and used the Mann-Whitney U rank sum test.Results: CBF-pGM outperformed M0-T1w (CC improvement 47.2% ± 22.0%; P < 0.001), and the non-rigid transformation outperformed rigid-body (20.6% ± 5.3%; P < 0.001). Masking only improved the M0-T1w rigid-body registration (14.5% ± 15.5%; P = 0.007).Conclusion: The choice of image registration strategy impacts ASL group analyses. The non-rigid transformation is promising but requires validation. CBF-pGM rigid-body registration without masking can be used as a default strategy. In patients with expansive perfusion deficits, M0-T1w may outperform CBF-pGM in sequences with high effective spatial resolution. BET-masking only improves M0-T1w registration when the M0 image has sufficient contrast.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:131-140. [ABSTRACT FROM AUTHOR]

Purpose: To test whether the combined use of 4D arterial spin labeling angiography (4D ASL) and contrast-enhanced magnetic resonance angiography (4D CE-MRA) can work as a prospective alternative to digital subtraction angiography (DSA) for the delineation of the arteriovenous malformation (AVM) nidus in stereotactic radiosurgery (SRS) planning.Materials and Methods: A custom 4D ASL sequence and a proof-of-concept software tool to integrate 4D ASL data to SRS planning were implemented. Ten AVM patients were scanned at 3T. Two observers independently contoured niduses in two separate sessions. Reference niduses were contoured using DSA, 4D ASL, and 4D CE-MRA. Test niduses were contoured using 4D ASL and 4D CE-MRA only. Reference and test niduses from both observers were compared in terms of volume, distance between centers of volumes (dCOV), and the Jaccard index (JI).Results: In volume comparisons, excellent intraobserver and interobserver agreements were obtained (intraclass correlation coefficients: 0.99 and 0.98, respectively). Median dCOV, JIs between reference and test niduses were 0.55 mm, 0.78 for Observer 1 and were 0.6 mm, 0.78 for Observer 2. None of the dCOV and JI parameters varied significantly among the delineation methods or the observers (P = 0.84, P = 0.39).Conclusion: Our preliminary results indicate that reproducibility of the target volumes with high agreement levels is achievable without using DSA. The combined use of high temporal resolution 4D ASL and high spatial resolution and vessel-to-background contrast 4D CE-MRA provided sufficient spatiotemporal angiographic information for the delineation of AVM niduses.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1718-1727. [ABSTRACT FROM AUTHOR]

Purpose: To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx).Materials and Methods: Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis.Results: In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy.Conclusion: ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether arterial spin labeling (ASL) MRI could detect renal hemodynamic impairment in diabetes mellitus (DM) along different stages of chronic kidney disease (CKD).Materials and Methods: Three Tesla (3T) ASL-MRI was performed to evaluate renal blood flow (RBF) in 91 subjects (46 healthy volunteers and 45 type 2 diabetic patients). Patients were classified according to their estimated glomerular filtration rate (eGFR) as group I (eGFR > 60 mL/min/1.73 m2 ), group II (60 ≥ eGFR>30 mL/min/1.73 m2 ), or group III (eGFR ≤ 30 mL/min/1.73 m2 ), to determine differences depending on renal function. Studies were performed at 3T using a 12-channel flexible body array combined with the spine array coil as receiver.Results: A 28% reduction in cortical RBF was seen in diabetics in comparison with healthy controls (185.79 [54.60] versus 258.83 [37.96] mL/min/100 g, P < 3 × 10-6 ). Differences were also seen between controls and diabetic patients despite normal eGFR and absence of overt albuminuria (RBF [mL/min/100 g]: controls=258.83 [37.96], group I=208.89 [58.83], P = 0.0018; eGFR [mL/min/1.73 m2 ]: controls = 95.50 [12.60], group I = 82.00 [20.76], P > 0.05; albumin-creatinine ratio [mg/g]: controls = 3.50 [4.45], group I = 17.50 [21.20], P > 0.05). A marked decrease in RBF was noted a long with progression of diabetic nephropathy (DN) through the five stages of CKD (χ2  = 43.58; P = 1.85 × 10-9 ). Strong correlation (r = 0.62; P = 4 × 10-10 ) was obtained between RBF and GFR estimated by cystatin C.Conclusion: ASL-MRI is able to quantify early renal perfusion impairment in DM, as well as changes according to different CKD stages of DN. In addition, we demonstrated a correlation of RBF quantified by ASL and GFR estimated by cystatin C.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1810-1817. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]