Arterial Spin Labeling Perfusion MRI Research Articles

Pharmacological manipulation of neurotransmitter activity induces disparate effects on cerebral blood flow and resting-state fluctuations

Abstract Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared. We assessed changes in resting measures of BOLD and ASL MRI in response to two neurotransmitter modulators: citalopram, a selective serotonin reuptake inhibitor, and alprazolam, a positive allosteric modulator of GABA type A receptor. Thirty healthy subjects were imaged in a placebo-controlled study, with N=20 subjects receiving each treatment as part of an incomplete block design. Time-averaged CBF images from ASL and measures of resting-state fluctuations of BOLD and ASL images were assessed for significant effects. Following acute citalopram administration, analysis of the ASL data showed a reduction in time-averaged regional CBF in regions associated with high levels of 5-HT1A receptor density. In contrast, following alprazolam administration, BOLD amplitude of low frequency fluctuations showed a highly significant and cortically widespread increase, consistent with the distribution of GABA-A receptors. Only a marginal decrease in ASL CBF was detected after alprazolam intake. BOLD and ASL are each sensitive to drugs targeting neurotransmitter systems, but appear to reflect different aspects of neural metabolism and the balance between excitatory and inhibitory activity. Accordingly, their combination may best capture the effects of neurotransmitter modulations, and thus be advantageous for pharmacological MRI studies.

Elevated cerebral perfusion in neonatal encephalopathy is associated with neurodevelopmental impairments.

Neonatal encephalopathy (NE) represents a primary cause of neonatal death and neurodevelopmental impairments. In newborns with NE, cerebral hyperperfusion is related to an increased risk of severe adverse outcomes, but less is known about the link between perfusion and mild to moderate developmental impairments or developmental delay. Using arterial spin labelling perfusion MRI, we investigated the link between perfusion in 36 newborns with NE and developmental outcome at 2 years. 53% of the infants demonstrated a normal outcome at 24 months, while two had cerebral palsy with impairments in cognitive, motor, and language domains, and three infants died. The remaining infants showed mild or moderate delays in development in one or two domains. Hyperperfusion across the whole brain was associated with more adverse outcome, including an increased risk of death or severe disability such as cerebral palsy. Among the surviving infants, higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. Hyperperfusion in infants with NE was associated with a more adverse outcome and lower cognitive outcome scores. In addition to severe adverse outcomes, altered perfusion is also related to mild to moderate impairment following HIE. Neonates with neonatal encephalopathy (NE) show increased cerebral perfusion globally, which is linked to a more adverse outcome. Higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. In addition to severe adverse outcomes altered perfusion is related to mild to moderate impairment following NE. To improve neurodevelopmental outcomes, it is important to improve our understanding of the factors influencing cerebral perfusion in infants with NE.

A Prospective Study on Perfusion MRI Changes in Intracranial Meningiomas Following Gamma Knife Therapy.

Radiosurgery plays an important role as a treatment modality for intracranial meningiomas. Perfusion MR imaging can be performed by using arterial spin-labeling (ASL) which is a relatively new and advanced technique. To assess the changes in perfusion parameters on ASL perfusion MRI in intracranial meningioma after radiosurgery and correlate with histopathological grade of meningioma. In this Prospective study done at the our institute over a period of 20 months (Jan 2016-Aug 2017), patients with intracranial meningiomas had perfusion MRI with ASL sequence on GE Optima 450W®, 1.5T MRI (GE Medical Systems) prior to GKT and at 6 months after GKT were included in the study. Twenty-seven patients were included in this study. Mean cerebral blood flow (CBF) was higher in angiomatous meningiomas. Though mean values of average CBF, maximum, minimum, and SD derived from the ASL MR perfusion were relatively higher in post GKT group as compared to those obtained in pre-GKT but it was not clinically significant. Mean baseline volume of whole cohort was 5.71 cm3 and decreased significantly post GKT in a follow up of 6 months to 5.59 cm3 (P value 0.0018). On comparing volumes of primary and secondary group, volumes were not found be significantly decreased in primary group (P value = 0.1361), 0.1361), but significantly reduced in secondary group (7.13 vs 7.034 cm3) (P value of = 0.0038). Our preliminary observations support ASL as a sensitive MRI sequence for the evaluation of meningioma perfusion patterns.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

ASL MRI Denoising via Multi Channel Collaborative Low-Rank Regularization.

Arterial spin labeling (ASL) perfusion MRI is the only non-invasive imaging technique for quantifying regional cerebral blood flow (CBF), which is a fundamental physiological variable. ASL MRI has a relatively low signal-to-noise-ratio (SNR). In this study, we proposed a novel ASL denoising method by simultaneously exploiting the inter- and intra-receive channel data correlations. MRI including ASL MRI data have been routinely acquired with multi-channel coils but current denoising methods are designed for denoising the coil-combined data. Indeed, the concurrently acquired multi-channel images differ only by coil sensitivity weighting and random noise, resulting in a strong low-rank structure of the stacked multi-channel data matrix. In our method, this matrix was formed by stacking the vectorized slices from different channels. Matrix rank was then approximately measured through the logarithm-determinant of the covariance matrix. Notably, our filtering technique is applied directly to complex data, avoiding the need to separate magnitude and phase or divide real and imaginary data, thereby ensuring minimal information loss. The degree of low-rank regularization is controlled based on the estimated noise level, striking a balance between noise removal and texture preservation. A noteworthy advantage of our framework is its freedom from parameter tuning, distinguishing it from most existing methods. Experimental results on real-world imaging data demonstrate the effectiveness of our proposed approach in significantly improving ASL perfusion quality. By effectively mitigating noise while preserving important textural information, our method showcases its potential for enhancing the utility and accuracy of ASL perfusion MRI, paving the way for improved neuroimaging studies and clinical diagnoses.

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

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

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol

IntroductionLoss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising...

Diffuse glioma molecular profiling with arterial spin labeling and dynamic susceptibility contrast perfusion MRI: A comparative study.

Evaluation of molecular markers (IDH, pTERT, 1p/19q codeletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side. Pretreatment MRI data from 90 patients diagnosed with diffuse glioma (54 men/36 female, 53.1±15.5 years, grades 2-4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH-mutation (n = 67), pTERT-mutation (n = 39), 1p/19q codeletion (n = 33), and MGMT promoter methylation (n = 31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters' performance in molecular marker detection. ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8 and DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q codeletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema. ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.

Deeply Accelerated Arterial Spin Labeling Perfusion MRI for Measuring Cerebral Blood Flow and Arterial Transit Time.

Cerebral blood flow (CBF) indicates both vascular integrity and brain function. Regional CBF can be non-invasively measured with arterial spin labeling (ASL) perfusion MRI. By repeating the same ASL MRI sequence several times, each with a different post-labeling delay (PLD), another important neurovascular index, the arterial transit time (ATT) can be estimated by fitting the acquired ASL signal to a kinetic model. This process however faces two challenges: one is the multiplicatively prolonged scan time, making it impractically for clinical use due to the escalated risk of motions; the other is the reduced signal-to-noise-ratio (SNR) in the long PLD scans due to the T1 decay of the labeled spins. Increasing SNR needs more repetitions which will further increase the total scan time. Currently, there lacks a way to accurately estimate ATT from a parsimonious number of PLDs. In this paper, we proposed a deep learning-based algorithm to reduce the number of PLDs and to accurately estimate ATT and CBF. Two separate deep networks were trained: one is designed to estimate CBF and ATT from ASL data with a single PLD; the other is to estimate CBF and ATT from ASL data with two PLDs. The models were trained and tested using the large Human Connectome Project multiple-PLD ASL MRI. Performance of the DL-based approach was compared to the traditional full dataset-based data fitting approach. Our results showed that ATT and CBF can be reliably estimated using deep networks even with one PLD.

Associations between ASL‐derived cerebrovascular health and cognitive performance: results from the Insight 46 study

AbstractBackgroundCardiovascular and cerebrovascular pathology may accelerate brain aging and cognitive decline. Structural cerebrovascular imaging biomarkers, such as white matter hyperintensities, reflect mostly irreversible accumulated damage. In contrast, cerebral blood flow (CBF), measured with arterial spin labelling (ASL) perfusion MRI, is a potential early haemodynamic biomarker of cognitive impairment. However, our understanding of physiological CBF variability and its relation with cognition is limited.MethodWe included 245 cognitively unimpaired participants from the Insight 46 birth cohort study, who underwent 3D T1‐weighted and pseudo‐continuous ASL‐MRI (labelling duration = 1800ms; post‐labelling delay = 1800ms) on a 3T Siemens Biograph mMR PET‐MRI scanner. Cognitive assessment included tests for logical memory (Wechsler Memory Scale‐Revised), associative memory (Face‐Name Associative Memory Exam), attention and processing speed (Digit‐symbol substitution and response inhibition test), non‐verbal reasoning (Matrix test), executive functioning (Choice Reaction Time), visuomotor integration (circle‐tracing task), and two composite scores (Mini‐Mental State Examination (MMSE) and the Preclinical Alzheimer Cognitive Composite).ResultSample characteristics are reported in Table 1. Associations were found between GM sCoV and MMSE (Male/Female ß = 0.74/‐0.75, p = 0.028, Figure 1), and GM sCoV and Logical Memory (Male/Female ß = 1.05/‐0.25, p = 0.005, Figure 2), but not between CBF and any cognitive scores (p&gt;0.05).ConclusionIn a cognitively unimpaired population, cognitive performance was associated with GM sCoV but not with other CBF parameters. However, in males, the relationship was opposite to what we expected. Further work should investigate to what extent this indicates macrovascular change occurs before perfusion alterations and could relate to future cognitive decline, and how they differ between sex.

ASL lexicon and reporting recommendations: A consensus report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

The 2015 consensus statement published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group and the European Cooperation in Science and Technology ( COST) Action ASL in Dementia aimed to encourage the implementation of robust arterial spin labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ASL Lexicon and Reporting Recommendations for perfusion imaging and analysis, aiming to (1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as for the physiological constants required for quantitative analysis; and (2) provide a community-endorsed recommendation of the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/papers. In this paper, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL, and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Disrupted resting-state functional connectivity and network topology in mild traumatic brain injury: an arterial spin labelling study.

Mild traumatic brain injury can cause different degrees of cognitive impairment and abnormal brain structure and functional connectivity, but there is still a lack of research on the functional connectivity and topological organization of cerebral blood flow fluctuations. This study explored the cerebral blood flow, functional connectivity and topological organization of the cerebral blood flow network in acute mild traumatic brain injury patients. In total, 48 mild traumatic brain injury patients and 46 well-matched healthy controls underwent resting-state arterial spin labelling perfusion MRI and neuropsychological assessments. The functional connectivity and topological organization of the cerebral blood flow network were analysed. Then, the correlation between the changes in cerebral blood flow network characteristics and cognitive function was explored. Acute mild traumatic brain injury patients showed decreased cerebral blood flow in the right insula and increased cerebral blood flow in the right inferior temporal gyrus and left superior temporal gyrus. Abnormal cerebral blood flow network connection patterns mainly occur in sensorimotor network, default mode network, cingulo-opercular network and occipital network-related regions. Furthermore, mild traumatic brain injury disrupted the topological organization of the whole brain, which manifested as (i) reduced global efficiency; (ii) abnormal degree centrality, betweenness centrality, nodal clustering coefficient and nodal efficiency; and (iii) decreased intermodular connectivity between the occipital network and sensorimotor network. Finally, the change in network topology was correlated with the cognitive score of the mild traumatic brain injury. This study provided evidence of abnormal functional connectivity and network topology based on cerebral blood flow in acute mild traumatic brain injury patients, revealing their potential use as early markers for mild traumatic brain injury, which may contribute to both disease diagnosis and assessment.

Cerebral blood flow patterns in preterm and term neonates assessed with pseudo-continuous arterial spin labeling perfusion MRI.

In preterm (PT) infants, regional cerebral blood flow (CBF) disturbances may predispose to abnormal brain maturation even without overt brain injury. Therefore, it would be informative to determine the spatial distribution of grey matter (GM) CBF in PT and full-term (FT) newborns at term-equivalent age (TEA) and to assess the relationship between the features of the CBF pattern and both prematurity and prematurity-related brain lesions. In this prospective study, we obtained measures of CBF in 66 PT (51 without and 15 with prematurity-related brain lesions) and 38 FT newborns through pseudo-continuous arterial spin labeling (pCASL) MRI acquired at TEA. The pattern of GM CBF was characterized by combining an atlas-based automated segmentation of structural MRI with spatial normalization and hierarchical clustering. The effects of gestational age (GA) at birth and brain injury on the CBF pattern were investigated. We identified 4 physiologically-derived clusters of brain regions that were labeled Fronto-Temporal, Parieto-Occipital, Insular-Deep GM (DGM) and Sensorimotor, from the least to the most perfused. We demonstrated that GM perfusion was associated with GA at birth in the Fronto-Temporal and Sensorimotor clusters, positively and negatively, respectively. Moreover, the presence of periventricular leukomalacia was associated with significantly increased Fronto-Temporal GM perfusion and decreased Insular-DGM perfusion, while the presence of germinal matrix hemorrhage appeared to mildly decrease the Insular-DGM perfusion. Prematurity and prematurity-related brain injury heterogeneously affect brain perfusion. ASL MRI may, therefore, have strong potential as a noninvasive tool for the accurate stratification of individuals at risk of domain-specific impairment.

White-Matter Lesions and Cortical Cerebral Blood Flow Evaluation by 3D Arterial Spin-Labeled Perfusion MRI in Asymptomatic Divers: Correlation with Patent Foramen Ovale Ocurrence.

Cerebral white-matter lesions (cWML) can be caused by dilation of Virchow-Robin spaces or may correspond to true lacunar ischemic lesions. The aim of our study was to evaluate in asymptomatic divers the relationship between the presence of patent foramen ovale (PFO) and cWML, as well as their possible effects on cortical cerebral blood flow (CBF) by magnetic resonance (MRI) through the arterial spin labeling (ASL) sequence. Transthoracic echocardiography was performed for the identification of PFO, and cerebral magnetic resonance including the 3D-ASL sequence for CBF quantification. Thirty-eight divers, with a mean age 45.8 ± 8.6 years, were included. Nineteen healthy volunteers, mean age 41 ± 15.2 years, served as the control group. A total of 28.9% of divers had completed more than 1000 dives. It was found that 26.3% of divers presented with PFO in the echocardiographic study. cWML was evidenced in 10.5% of diver MRI studies. There was no statistically significant relationship between the presence of PFO and cWML (p = 0.95). We observed a lower blood flow in all brain areas assessed by the 3D-ASL sequence in the group of divers, compared with the control group. We did not find statistical differences in CBF as a function of the presence or absence of PFO, number of dives, or cWML evidence.

Hypo- and hyper-perfusion in MCI and AD identified by different ASL MRI sequences.

Arterial spin labeling (ASL) perfusion MRI has been increasingly used in Alzheimer's Disease (AD) research. However, ASL MRI sequences differ greatly in terms of arterial blood signal preparations and data acquisition strategies, both leading to a large difference of signal-to-noise ratio (SNR). It is of great translational importance to compare the several widely used ASL MRI sequences regarding sensitivity of ASL measured cerebral blood flow (CBF) for detecting the between-group difference across the AD continuum. To this end, this study compared three ASL MRI sequences in AD research, including the 2D Pulsed ASL (PASL), 3D Background Suppressed (BS) PASL, and 3D BS Pseudo-Continuous ASL (PCASL). We used data from 100 healthy and cognitively normal elderly control (NC) subjects, 75 patients with mild cognitive impairment (MCI), and 57 Alzheimer's disease (AD) subjects from the AD neuroimaging initiative (ADNI). Both cross-sectional perfusion difference and perfusion versus clinical assessment correlations were examined. The major findings included: 3D PCASL sequence identified stronger patient versus control CBF/rCBF differences than 2D PASL and 3D PASL; MCI showed reduced CBF and CBF redistribution; CBF in orbito-frontal cortex presents a new U-shape change pattern from normal aging to MCI and to AD; 3D PCASL identified a negative rCBF to memory correlation while 2D PASL showed a positive correlation.

Hypoperfusion Precedes Tau Deposition in the Entorhinal Cortex: A Retrospective Evaluation of ADNI-2 Data.

Tau deposition in the entorhinal cortex is the earliest pathological feature of Alzheimer's disease (AD). However, this feature has also been observed in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI). The precise pathophysiology for the development of tau deposition remains unclear. We hypothesized that reduced cerebral perfusion is associated with the development of tau deposition. A subset of the Alzheimer's Disease Neuroimaging Initiative data set was utilized. Included patients had undergone arterial spin labeling perfusion MRI along with [18F]flortaucipir tau PET at baseline, within 1 year of the MRI, and a follow-up at 6 years. The association between baseline cerebral blood flow (CBF) and the baseline and 6-year tau PET was assessed. Univariate and multivariate linear modeling was performed, with p<0.05 indicating significance. Significant differences were found in the CBF between patients with AD and MCI, and CN individuals in the left entorhinal cortex (p=0.013), but not in the right entorhinal cortex (p=0.076). The difference in maximum standardized uptake value ratio between 6 years and baseline was significantly and inversely associated with the baseline mean CBF (p=0.042, R²=0.54) in the left entorhinal cortex but not the right entorhinal cortex. Linear modeling demonstrated that CBF predicted 6-year tau deposition (p=0.015, R²=0.11). The results of this study suggest that a reduction in CBF at the entorhinal cortex precedes tau deposition. Further work is needed to understand the mechanism underlying tau deposition in aging and disease.

The value of arterial spin labelling (ASL) perfusion MRI in the assessment of post-treatment progression in adult glioma: A systematic review and meta-analysis.

The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects. Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed. This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] (p < .00001). The maximum perfusion indices (rCBFmax and CBFmax) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] (p < .00001) and 1.56 [95% CI 0.79, 2.33] (p < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBFmax and CBFmax, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95]. These results suggest that ASL quantitative biomarkers, particularly rCBFmax and CBFmax, have the potential to discriminate between glioma progression and therapy-induced changes.

The longitudinal evolution of cerebral blood flow in children with tuberous sclerosis assessed by arterial spin labeling magnetic resonance imaging may be related to cognitive performance.

To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes. Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF. Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load. Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay. • Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay.

P15.06.B Influence of arterial transit time delays on the differentiation between tumor progression and pseudo-progression in glioblastoma by arterial spin labeling MRI

Abstract Background Perfusion MRI by Arterial Spin Labeling (ASL) and Dynamic Susceptibility Contrast (DSC) has shown its potential for differentiating tumor progression from pseudo-progression in glioblastoma patients. The ASL scans can be affected by arterial transit time (ATT) delays, which could be caused by treatment effects due to concomitant radiochemotherapy. A prolonged ATT is present as apparent signal increase in the large arteries due to labeled spins still residing within the vasculature, leading to underestimation of tissue perfusion and thus potentially affecting clinical decision-making. The research questions were: 1) Do delayed ATTs lead to a difference in the visual assessment of ASL perfusion (normal/increased) maps compared to DSC-MRI?; 2) Does the radiological evaluation (progression vs. pseudo-progression) of ASL and DSC perfusion maps differ when ATT artifacts are present?; 3) Do delayed ATTs affect the predictive value of ASL-MRI scans 3 months post-radiotherapy for detecting true disease progression? Material and Methods This retrospective, single-center study included 68 adult patients with histologically confirmed glioblastoma who received postoperative radio(chemo)therapy. ASL and DSC scans were acquired 3 months post-radiotherapy as part of routine clinical follow-up. The perfusion data were visually scored by a neuroradiologist who determined presence/absence of ATT artifacts and their severity (%), perfusion of the enhancing tumor lesion and the radiological evaluation of tumor progression versus pseudo-progression. Presence of true disease progression was determined by follow-up of clinical data until 9 months post-radiotherapy available for 49/68 patients. Logistic regression was performed with gender, age, treatment type and tumor genetic status as covariates to assess the predictive value of ASL. Results In 78% of the patients ATT artifacts were present. No statistically significant association between the agreement of the perfusion maps and presence of ATT artifacts was found, but presence of ATT artifacts lowered the agreement between the DSC and ASL radiological evaluation. The logistic regression analysis showed that the ASL-based radiological score could not predict true disease progression, whereas higher age and unmethylated MGMT gene were associated with progression. Presence of ATT artifacts was not associated with tumor progression. Conclusion The presence of delayed ATT in ASL data seems to impact the radiological evaluation of ASL data, steering interpretation towards tumor progression (as compared to the DSC evaluation), whereas in patients without ATT artifacts ASL and DSC provide more similar radiological scores. Therefore, it is highly recommended to consider these artifacts when interpreting ASL perfusion MRI to differentiate between tumor progression and pseudo-progression in glioblastoma patients.

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.