Arterial Spin Labeling Cerebral Blood Flow Research Articles

Comparison of ASL and DSC perfusion methods in the evaluation of response to treatment in patients with a history of treatment for malignant brain tumor

ObjectivePerfusion MRI is of great benefit in the post-treatment evaluation of brain tumors. Interestingly, dynamic susceptibility contrast-enhanced (DSC) perfusion has taken its place in routine examination for this purpose. The use of arterial spin labeling (ASL), a perfusion technique that does not require exogenous contrast material injection, has gained popularity in recent years. The aim of the study was to compare two different perfusion techniques, ASL and DSC, using qualitative and quantitative measurements and to investigate the diagnostic effectiveness of both. The fact that the number of patients is higher than in studies conducted with 3D pseudo-continious ASL (pCASL), the study group is heterogeneous as it consists of patients with both metastases and glial tumors, the use of 3D Turbo Gradient Spin Echo (TGSE), and the inclusion of visual (qualitative) assessment make our study unique.MethodsNinety patients, who were treated for malignant brain tumor, were enrolled in the retrospective study. DSC Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF) and ASL CBF maps of each case were obtained. In qualitative analysis, the lesions of the cases were visually classified as treatment-related changes (TRC) and relapse/residual mass (RRT). In the quantitative analysis, three regions of interest (ROI) measurements were taken from each case. The average of these measurements was compared with the ROI taken from the contralateral white matter and normalized values (n) were obtained. These normalized values were compared across events.ResultsUncorrected DSC normalized CBV (nCBV), DSC normalized CBF (nCBF) and ASL nCBF values of RRT cases were higher than those of TRC cases (p < 0.001). DSC nCBV values were correlated with DSC nCBF (r: 0.94, p < 0.001) and correlated with ASL nCBF (r: 0.75, p < 0.001). Similarly, ASL nCBF was positively correlated with DSC nCBF (r: 0.79 p < 0.01). When the ROC curve parameters were evaluated, the cut-off values were determined as 1.211 for DSC nCBV (AUC: 0.95, 93% sensitivity, 82% specificity), 0.896 for DSC nCBF (AUC; 0.95, 93% sensitivity, 82% specificity), and 0.829 for ASL nCBF (AUC: 0.84, 78% sensitivity, 75% specificity). For qualitative evaluation (visual evaluation), inter-observer agreement was found to be good for ASL CBF (0.714), good for DSC CBF (0.790), and excellent for DSC CBV (0.822). Intra-observer agreement was also evaluated. For the first observer, good agreement was found in ASL CBF (0.626, 70% sensitive, 93% specific), in DSC CBF (0.713, 76% sensitive, 95% specific), and in DSC CBV (0.755, 87% sensitive - 88% specific). In the second observer, moderate agreement was found in ASL CBF (0.584, 61% sensitive, 97% specific) and DSC CBF (0.649, 65% sensitive, 100% specific), and excellent agreement in DSC CBV (0.800, 89% sensitive, 90% specific).ConclusionIt was observed that uncorrected DSC nCBV, DSC nCBF and ASL nCBF values were well correlated with each other. In qualitative evaluation, inter-observer and intra-observer agreement was higher in DSC CBV than DSC CBF and ASL CBF. In addition, DSC CBV is found more sensitive, ASL CBF and DSC CBF are found more specific for both observers. From a diagnostic perspective, all three parameters DSC CBV, DSC CBF and ASL CBF can be used, but it was observed that the highest rate belonged to DSC CBV.

Pathologic burden goes with the flow: MRI perfusion and pathologic burden in frontotemporal lobar degeneration due to tau

Abstract Regional cerebral blood flow (CBF) changes quantified using arterial spin labeling (ASL) are altered in neurodegenerative disorders such as frontotemporal lobar degeneration due to tau (FTLD-tau), but the relationship between ASL CBF and pathologic burden has not been assessed. Our objective was to determine whether regional ASL CBF acquired antemortem in patients with FTLD-tau is related to pathologic burden measured at autopsy in those same regions in the same patients to directly test the imaging-pathology relationship. In this case-control study, data were acquired between 3/4/2010 and 12/16/2018. Data processing and analysis were completed in 2023. Twenty-one participants with autopsy-confirmed FTLD-tau (N = 10 women, mean[SD] age 67.9[7.56] years) along with 25 control participants (N = 15 women, age 64.7[7.53]) were recruited through the cognitive neurology clinic at the University of Pennsylvania. All participants had ASL and T1-weighted images collected antemortem. ASL images were processed to estimate CBF and T1-weighted images were processed to estimate gray matter (GM) volumes in regions corresponding to regions sampled postmortem. Digital quantification of pathologic burden was performed to find the percent area occupied (%AO) of pathologic FTLD-tau at autopsy. Regional CBF and GM volumes were both related to pathologic burden in the same regions from the same participants. Strengths of model fits of imaging measures to pathologic burden were compared. CBF in FTLD-tau and controls were compared, with results considered significant at p &amp;lt; 0.05 after Bonferroni correction. We found that relative to controls, FTLD-tau displayed hypoperfusion in anterior cingulate, orbitofrontal, middle frontal, and superior temporal regions, as well as angular gyrus. For patients with FTLD-tau regional CBF was significantly associated with pathologic burden (beta = -1.07, t = -4.80, p &amp;lt; 0.005). Models including both GM volume and CBF provided significantly better fits to pathologic burden data than single modality models (p &amp;lt; 0.05, Bonferroni-corrected). Our results indicate that reduced CBF measured using ASL MRI is associated with increased pathologic burden in FTLD-tau and adds complementary predictive value of pathologic burden to structural MRI.

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0± 1.8 vs. 13.9± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Automated Quality Evaluation Index for Arterial Spin Labeling Derived Cerebral Blood Flow Maps.

Arterial spin labeling (ASL) derived cerebral blood flow (CBF) maps are prone to artifacts and noise that can degrade image quality. To develop an automated and objective quality evaluation index (QEI) for ASL CBF maps. Retrospective. Data from N = 221 adults, including patients with Alzheimer's disease (AD), Parkinson's disease, and traumatic brain injury. Pulsed or pseudocontinuous ASL acquired at 3 T using non-background suppressed 2D gradient-echo echoplanar imaging or background suppressed 3D spiral spin-echo readouts. The QEI was developed using N = 101 2D CBF maps rated as unacceptable, poor, average, or excellent by two neuroradiologists and validated by 1) leave-one-out cross validation, 2) assessing if CBF reproducibility in N = 53 cognitively normal adults correlates inversely with QEI, 3) if iterative discarding of low QEI data improves the Cohen's d effect size for CBF differences between preclinical AD (N = 27) and controls (N = 53), 4) comparing the QEI with manual ratings for N = 50 3D CBF maps, and 5) comparing the QEI with another automated quality metric. Inter-rater reliability and manual vs. automated QEI were quantified using Pearson's correlation. P < 0.05 was considered significant. The correlation between QEI and manual ratings (R = 0.83, CI: 0.76-0.88) was similar (P = 0.56) to inter-rater correlation (R = 0.81, CI: 0.73-0.87) for the 2D data. CBF reproducibility correlated negatively (R = -0.74, CI: -0.84 to -0.59) with QEI. The effect size comparing patients and controls improved (R = 0.72, CI: 0.59-0.82) as low QEI data was discarded iteratively. The correlation between QEI and manual ratings (R = 0.86, CI: 0.77-0.92) of 3D ASL was similar (P = 0.09) to inter-rater correlation (R = 0.78, CI: 0.64-0.87). The QEI correlated (R = 0.87, CI: 0.77-0.92) significantly better with manual ratings than did an existing approach (R = 0.54, CI: 0.30-0.72). Automated QEI performed similarly to manual ratings and can provide scalable ASL quality control. 2 TECHNICAL EFFICACY: Stage 1.

Dual independent pathway‐densely connected residual network with dilated convolution‐based arterial spin labeling MRI image reconstruction with minimum label‐control pairs

AbstractArterial spin labeling (ASL) is a non‐invasive MRI technique widely used to measure cerebral blood flow (CBF), but it suffers from poor SNR, requiring the acquisition of a large number of multiple Label‐Control (L‐C) pairs at the expense of prolonged acquisition time. This work proposed a novel deep learning network to reconstruct the ASL CBF map using the minimum number of L‐C pairs. A dataset comprising 72 normal ASL raw images with 52 L‐C pairs is obtained from ADNI2. The mean CBF map, derived from 52 L‐C pairs with Gaussian smoothing and outlier cleaning, serves as the reference. The mean CBF images obtained from randomly selected 10 pairs per subject, without preprocessing, are employed as input for the proposed model. A novel data augmentation technique for model training, leveraging the characteristics of ASL L‐C pairs, is implemented. The accuracy and reproducibility of the reconstructed ASL CBF map were assessed with various state‐of‐the‐art methods on both normal and Alzheimer's Disease (AD) data. The proposed model surpasses state‐of‐the‐art methods, yielding PSNR = 23.9542, SSIM = 0.81499, and Lin's CCC = 0.9168 for the ASL CBF map with 10 L‐C pairs in normal data. For AD patients, the model achieves PSNR of 22.5932, SSIM of 0.80923, and Lin's CCC of 0.9078. The Bland–Altman plot, using the radiologist's manual GMCBF ROI, consistently aligns the estimated and reference CBF values. The novel data augmentation technique improved the ASL CBF map quantification accuracy with Lin's CCC &gt;0.9. The proposed work is a promising approach to reconstructing the ASL CBF map using a minimum number of ASL LC pairs that can lead to low image acquisition time with a reduction in motion artifacts. The use of a novel data augmentation approach, utilizing the properties of ASL L‐C pairs, allows for the generation of a large dataset for further experimentation and analysis.

Validation of early‐frame 18F‐FDG PET for CBF quantification: Comparison to simultaneous eASL measurements in memory patients

AbstractBackgroundThis study aimed to validate early [18F]‐FDG (eFDG) imaging for the quantification of cerebral blood flow (CBF), enabling dual‐marker imaging of perfusion and metabolism with a single tracer.Method19 participants with memory concerns underwent simultaneous [18F]‐FDG PET and multi delay pseudo‐continuous arterial spin labeling (eASL) MR imaging on a hybrid 3T PET/MRI scanner. eFDG‐CBF maps were generated from the first 30s, 60s, 120s and 300s after injection, and measurements were compared to ASL‐CBF using voxel‐wise cross correlation and concordance correlation for 7 regions derived from the MNI‐structural atlas.ResultHighest voxel‐wise cross‐correlation to ASL‐CBF maps were reported for 300s (5 min) eFDG (r = 0.77).Concordance correlation (CC) values were strong in all ROIs, ranging from (CC = 0.88) to (CC = 0.65) in temporal and occipital regions respectively. Mean of measurements in all ROIs were in good agreement between eFDG and ASL CBF maps, with a reported voxel‐wise mean absolute error of ±6.73 ml/100g/min between two maps.ConclusionBy simultaneous measurement of hemodynamics across modalities with a TOF‐enabled PET/MRI, we were able to demonstrate that eFDG PET is a reliable measure in mapping CBF based on strong inter‐modality correlation with ASL‐CBF, irrespective of pathophysiological variations in memory patients.

How can we differentiate supratentorial tumor recurrence from postradiation imaging changes in children treated for primary malignant brain tumors?

Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

Comparison of arterial spin labeling perfusion with dynamic susceptibility contrast perfusion in Moyamoya disease.

Moyamoya disease (MMD) leads to frequent ischemic/hemorrhagic manifestations. Our aim was to compare findings of arterial spin labeling (ASL) with dynamic susceptibility contrast (DSC) perfusion in patients of MMD. Patients diagnosed as MMD underwent magnetic resonance imaging with ASL and DSC perfusion sequences. Perfusion in bilateral anterior cerebral artery and middle cerebral artery territories at two levels (level of thalami and centrum semiovale) was graded as normal (score 1), or reduced (score 2) on DSC and ASL cerebral blood flow (CBF) maps by comparison with normal cerebellar perfusion. Time to peak (TTP) maps of DSC perfusion were also qualitatively scored as normal (score 1), or increased (score 2) similarly. Correlation between scores of ASL, CBF, DSC, CBF, and DSC, TTP maps was assessed by using Spearman's rank correlation. Among the 34 patients, we did not find any significant correlation between the ASL CBF maps and DSC CBF maps (r = -0.028, P = 0.878), mean matching index 0.39 ± 0.31, whereas significant correlation was noted between the ASL CBF maps and DSC TTP maps (r = 0.58, P = 0.0003), mean matching index 0.79 ± 0.26. ASL CBF underestimated the perfusion compared to DSC perfusion. ASL perfusion CBF maps do not match the DSC perfusion CBF maps and rather match the TTP maps of DSC perfusion. This is explained by inherent problems in estimation of CBF in these techniques because of delay in arrival of label (in ASL perfusion) or contrast bolus (in DSC perfusion) due to the presence of stenotic lesions.

The Utility of Arterial Transit Time Measurement for Evaluating the Hemodynamic Perfusion State of Patients with Chronic Cerebrovascular Stenosis or Occlusive Disease: Correlative Study between MR Imaging and 15O-labeled H2O Positron Emission Tomography.

To verify whether arterial transit time (ATT) mapping can correct arterial spin labeling-cerebral blood flow (ASL-CBF) values and to verify whether ATT is a parameter that correlates with positron emission tomography (PET)-oxygen extraction fraction (OEF) and PET-mean transit time (MTT). Eleven patients with unilateral major cerebral artery stenosis or occlusion underwent MRI and PET in the chronic or asymptomatic phase. ASL-MRI acquisitions were conducted with each of two post-label delay (PLD) settings (0.7s and 2.0s) using a pseudo-continuous ASL pulse sequence and 3D-spin echo spiral readout with vascular crusher gradient. ATT maps were obtained using a low-resolution pre-scan approach with five PLD settings. Using the ASL perfusion images and ATT mapping, ATT-corrected ASL-CBF images were obtained. Four kinds of ASL-CBF methods (PLD 0.7s with or without ATT correction and PLD 2.0s with or without ATT correction) were compared to PET-CBF, using vascular territory ROIs. ATT and OEF were compared for all ROIs, unaffected side ROIs, and affected side ROIs, respectively. ATT and MTT were compared by the ratio of the affected side to the unaffected side. Transit time-based ROIs were used for the comparison with ATT. Comparing ASL-CBF and PET-CBF, the correlation was higher with ATT correction than without correction, and for a PLD of 2.0s compared with 0.7s. The best correlation was for PLD of 2.0s with ATT correction (R2 = 0.547). ROIs on the affected side showed a low but significant correlation between ATT and PET-OEF (R2 = 0.141). There was a low correlation between the ATT ratio and the MTT ratio (R2 = 0.133). Low-resolution ATT correction may increase the accuracy of ASL-CBF measurements in patients with unilateral major cerebral artery stenosis or occlusion. In addition, ATT itself might have a potential role in detecting compromised hemodynamic state.

Reply: Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study.

We have read with great interest the letter from Long et al. regarding our article.1 Their letter stated two methodological concerns to which we will respond. The first concern is that objective criteria are missing for true trigonocephaly or benign metopic ridge. We only included patients with moderate to severe trigonocephaly according to the definitions of Birgfeld et al.2 In their article, Birgfeld et al. provide a phenotypical distinction between benign metopic ridge and metopic synostosis, as well as illustrative photographs with corresponding computed tomographic imaging.2 Cho et al.3 and Anolik et al.4 described computed tomographic measures to assess severity of metopic synostosis. In both studies, the cut-off point to determine surgical indication remained subjective, and poor consensus for the intermediate presentation of metopic craniosynostosis was found. In addition, Sisti et al.5 recently reviewed all literature in PubMed on trigonocephaly, relating to 15 anthropometric cranial measurements for surgical indications. They found that most articles have a lack of diagnostic criteria for trigonocephaly. At our center, the decision for surgery is made through shared decision-making with parents. In 2021, this resulted in surgery for 14 patients (moderate or severe presentation) and a conservative treatment for 40 patients (18 with mild presentation and 22 with moderate or severe presentation). The second concern Long et al. raise is the potential blunting effect of sevoflurane on cerebral blood flow (CBF). If there is a blunting effect, a similar effect on both patients and controls is expected. In our previous arterial spin labeling study in patients with syndromic craniosynostosis using the same sedation protocol, we found a difference between the groups.6 This suggests that the normal findings in patients with trigonocephaly reflect normal CBF. Very few studies have investigated the influence of anesthesia on arterial spin labeling CBF in the pediatric population. Carsin-Vu et al.7 included 84 subjects ranging in age from 6 months to 15 years and showed no significant CBF changes with sevoflurane in comparison to general anesthesia. Kaisti et al.8 showed in eight healthy male patients (age range, 20 to 26 years) that sevoflurane reduced regional CBF less than propofol did. Without sedation, scanning of one sequence is possible, because of the limited timeframe. However, more sequences, as in our protocol, requires a longer time period. Without sedation, motion artifacts would make it impossible to analyze. Finally, Long et al. mention that cerebral perfusion is a limited measure of neurodevelopment and that functional magnetic resonance imaging (MRI) studies in patients with scaphocephaly have shown a difference in functional brain connectivity compared with controls. However, there is still a lot unknown about the optimal method of scanning, reproducibility, and interpretation of functional MRI results. Finding a difference in connectivity in functional MRI studies would be at the same level of evidence as the arterial spin labeling brain MRI study.9 To conclude, our study further supports our hypothesis that surgery for trigonocephaly is rarely indicated functionally. Parents should be informed about the unknown added value of surgery regarding raised intracranial pressure and brain perfusion. Comparative research on outcome of conservative versus surgical treatment of moderate to severe trigonocephaly is needed to establish clinical guidelines. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Catherine A. de Planque, MDDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands Jan Petr, PhDHelmholtz-Zentrum Dresden-RossendorfInstitute of Radiopharmaceutical Cancer ResearchDresden, Germany Linda Gaillard, MDDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands Henk J. M. M. Mutsaerts, MD, PhDVrije Universiteit AmsterdamAmsterdam NeuroscienceAmsterdam, The Netherlands Marie-Lise C. van Veelen, MD, PhDDepartment of Neurosurgery Sarah L. Versnel, MD, PhDDepartment of Plastic, Reconstructive Surgery, and Hand Surgery Marjolein H. G. Dremmen, MDDepartment of Radiology and Nuclear Medicine Irene M. J. Mathijssen, MD, PhD, MBA-HDepartment of Plastic, Reconstructive Surgery, and Hand SurgeryErasmus MC-Sophia Children’s HospitalUniversity Medical Center RotterdamRotterdam, The Netherlands

Associations of intracranial artery length and branch number on non-contrast enhanced MRA with cognitive impairment in individuals with carotid atherosclerosis.

Developing novel risk markers for vascular contributions to cognitive impairment and dementia is important. This study aimed to extract total length, branch number and average tortuosity of intracranial distal arteries (A2, M2, P2 and more distal) from non-contrast enhanced magnetic resonance angiography (NCE-MRA) images, and explore their associations with global cognition. In 29 subjects (aged 40–90 years) with carotid atherosclerotic disease, the 3 intracranial vascular features on two NCE-MRA techniques (i.e. time of flight, TOF and simultaneous non-contrast angiography and intraplaque hemorrhage, SNAP) were extracted using a custom-developed software named iCafe. Arterial spin labeling (ASL) and phase contrast (PC) cerebral blood flow (CBF) were measured as references. Linear regression was performed to study their associations with global cognition, measured with the Montreal Cognitive Assessment (MoCA). Intracranial artery length and number of branches on NCE-MRA, ASL CBF and PC CBF were found to be positively associated with MoCA scores (P < 0.01). The associations remained significant for artery length and number of branches on NCE-MRA after adjusting for clinical covariates and white matter hyperintensity volume. Further adjustment of confounding factors of ASL CBF or PC CBF did not abolish the significant association for artery length and number of branches on TOF. Our findings suggest that intracranial vascular features, including artery length and number of branches, on NCE-MRA may be useful markers of cerebrovascular health and provide added information over conventional brain blood flow measurements in individuals with cognitive impairment.

Patch tensor decomposition and non-local means filter-based hybrid ASL image denoising

BackgroundArterial spin labeling magnetic resonance imaging (ASL MRI) is a noninvasive technique to measure cerebral blood flow (CBF). It is widely used in the study of neurodegenerative diseases. Image denoising is an important step in ASL image processing because the signal-to-noise ratio (SNR) of an ASL CBF perfusion image is very small. New methodWe propose a new ASL image denoising method that exploits patch-based low-rank and sparse tensor decomposition and a non-local means filter. Comparison with existing methodsThe proposed method was compared with two existing ASL denoising methods: component-based noise correction method (CompCor) and low-rank and sparse matrix decomposition-based ASL image denoising method (LS-ASLd). ResultsVarious image quality measures, namely SNR, tSNR and ASL CBF variance, show that the proposed method is more effective than existing ASL denoising methods. The proposed method was used to denoise images from a resting state ASL dataset to compute brain functional connectivity (FC) and images from a task-related ASL dataset to identify brain activation. The results show that the proposed denoising method is more effective to enhance the sensitivity of ASL CBF series when undertaking CBF time series-based FC analysis and task activation detection. ConclusionsAssessment of the performance of the proposed hybrid ASL CBF image denoising method confirms that it is especially well-suited to FC analysis and sensorimotor task analysis.

Differences in cerebral blood flow measurement using arterial spin labeling MRI between patients with moyamoya disease and patients with arteriosclerotic cerebrovascular disease.

It is unclear whether the accuracy of arterial spin labeling (ASL) magnetic resonance imaging (MRI) is the same between moyamoya disease (MMD), which is known to have markedly elevated cerebral blood volume (CBV), and atherosclerotic intracranial arterial stenosis (AS), which has relatively less elevated CBV. To investigate how the differences in hemodynamics affect measurement of ASL-cerebral blood flow (CBF) using ASL for patients with MMD and AS. Fourteen MMD and ten AS patients were evaluated with ASL-MRI, magnetic resonance angiography (MRA), and 15O-gas positron emission computed tomography (PET). The regional CBF values of ASL using two post-labeling delays (PLDs; 1525 ms and 2525 ms) were compared with the PET-derived CBF, CBV, and mean transit time (MTT). Corresponding anterior circulation results were evaluated by flow territory map-based analysis. The correlation between the ASL-CBF values (2525 ms) and PET-CBF declined in the MMD group (r = 0.28; P < 0.01), while the AS group showed good correlation (r = 0.77; P < 0.01). In the MMD group, the ASL-CBF values (2525 ms) overestimated the PET-CBF values as the regional CBV values increased (r = 0.35; P < 0.01). When the regions of interest were divided into two subgroups according to the degree of arterial stenosis by MRA, the correlation coefficient between the ASL-CBF (2525 ms) and PET-CBF values improved (mild stenosis: r = 0.36; P = 0.06; severe stenosis: r = 0.51; P < 0.01). The accuracy of CBF measurements using ASL-MRI differed between patients with MMD and AS. The prominent increase of CBV and the degree of arterial stenosis may have affected the accuracy of ASL-CBF in patients with MMD.

Cerebral perfusion in posterior reversible encephalopathy syndrome measured with arterial spin labeling MRI

Background and purposeThe pathophysiologic basis of posterior reversible encephalopathy syndrome (PRES) remains controversial. Hypertension (HTN)-induced autoregulatory failure with subsequent hyperperfusion is the leading hypothesis, whereas alternative theories suggest vasoconstriction-induced hypoperfusion as the underlying mechanism. Studies using contrast-based CT and MR perfusion imaging have yielded contradictory results supporting both ideas. This work represents one of the first applications of arterial spin labeling (ASL) to evaluate cerebral blood flow (CBF) changes in PRES. Materials and methodsAfter obtaining Institutional Review Board approval, MRI reports at our institution from 07/2015 to 09/2020 were retrospectively searched and reviewed for mention of “PRES” and “posterior reversible encephalopathy syndrome.” Of the resulting 103 MRIs (performed on GE 1.5 Tesla or 3 Tesla scanners), 20 MRIs in 18 patients who met the inclusion criteria of clinical and imaging diagnosis of PRES and had diagnostic-quality pseudocontinuous ASL scans were included. Patients with a more likely alternative diagnosis, technically non-diagnostic ASL, or other intracranial abnormalities limiting assessment of underlying PRES features were excluded. Perfusion in FLAIR-affected brain regions was qualitatively assessed using ASL and characterized as hyperperfusion, normal, or hypoperfusion. Additional quantitative analysis was performed by measuring average gray matter CBF in abnormal versus normal brain regions. ResultsHTN was the most common PRES etiology (65%). ASL showed hyperperfusion in 13 cases and normal perfusion in 7 cases. A hypoperfusion pattern was not identified. Quantitative analysis of gray matter CBF among patients with visually apparent hyperperfusion showed statistically higher perfusion in affected versus normal appearing brain regions (median CBF 100.4 ml/100 g-min vs. 61.0 ml/ 100 g-min, p < 0.001). ConclusionElevated ASL CBF was seen in the majority (65%) of patients with PRES, favoring the autoregulatory failure hypothesis as a predominant mechanism. Our data support ASL as a practical way to assess and noninvasively monitor cerebral perfusion in PRES that could potentially alter management strategies.

Arterial Transit Time-Based Multidelay Combination Strategy Improves Arterial Spin Labeling Cerebral Blood Flow Measurement Accuracy in Severe Steno-Occlusive Diseases.

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. 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. Prospective. Moyamoya (n=10) and atherosclerotic diseases (n= 8). A 3.0T/3DT1 -weighted and ASL. 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. Pearson's correlation coefficient, repeated-measures analysis of variance, t-test. P< 0.05 was considered significant. 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). 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. 1 TECHNICAL EFFICACY: Stage 2.

243 Adverse relationships between sleep apnea, white matter integrity and perfusion is attenuated in more physically fit older adults

Abstract Introduction White matter (WM) integrity declines with age and is sensitive to vascular risk modifiers, such as exercise. Sleep apnea is believed to contribute to cerebral white matter change via intermittent hypoxia-induced alterations to cerebral blood flow resulting in cerebrovascular shearing. Existing literature highlights the relationships between poor sleep and numerous adverse health outcomes, including risk for cardiovascular disease and dementia. Conversely, exercise seems to have a positive effect on both brain structure and function. Here we examine a potential interaction between sleep apnea severity and cardiorespiratory fitness (characterized by a gender-specific Non-Exercise CardioRespiratory Fitness Measure, NECRFM) as predictors of MRI measures of brain WM integrity and cerebral blood flow (CBF) in a sample of non-demented older adult participants of the Wisconsin Sleep Cohort (WSC). Methods Cross-sectional linear models using data from a subset of 124 WSC participants (50% female; mean age[range]=67.6 [49.6, 85.3]) examined the relationship between sleep apnea severity (apnea-hypopnea index, AHI) and cardiorespiratory fitness in predicting MRI-assessed total WM and lesion volumes, WM hyperintensities (WMHs; a marker of small vessel disease in the brain) and Arterial Spin Labeling (ASL) CBF, controlling for age, sex, BMI, education, and hypertension. Results Greater sleep apnea severity was associated more strongly with both total lesion and WMH loads in less fit compared to more fit persons (p’s&amp;lt;0.05) in the absence of significant differences in total WM volume. Regional perfusion revealed higher CBF in the angular gyrus, middle frontal cortex, and superior frontal gyrus and lower CBF in the anterior cingulate gyrus and the hippocampus of more fit compared to less fit persons (p’s&amp;lt; 0.05), in the absence of differences in mean global perfusion. Conclusion Overall, our results suggest that better general fitness may attenuate negative brain health outcomes related to poor sleep. We highlight an important relationship between brain health and modifiable behavioral factors, namely sleep and fitness, that have the potential to help maintain or improve brain integrity with age. Support (if any) This work was supported by United States National Institutes of Health grants R01AG062167, R01AG058680, R01HL62252, 1R01AG036838 and 1UL1RR025011.

Vessel length on SNAP MRA and TOF MRA is a potential imaging biomarker for brain blood flow

PurposeTo explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references. MethodsIn a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements. ResultsUnder the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P < 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P < 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P < 0.001). ConclusionThe results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.

NFB-04. EXAMINING DIFFUSION, ARTERIAL SPIN-LABELED PERFUSION, AND VOLUMETRIC CHANGES IN THE NEUROFIBROMATOSIS TYPE 1 BRAIN USING AN ATLAS-BASED, MULTI-PARAMETRIC APPROACH

BACKGROUNDNeurofibromatosis Type 1 (NF1) is a multisystem disorder with wide ranging clinical implications. Patients may present with macrocephaly, stroke, and cognitive deficits, all of which may impede normal neural development. We applied atlas-based, multi-parametric MRI analysis of regional brain to evaluate diffusion, arterial spin-labeled (ASL) perfusion, and volumetric changes in children with NF1.METHODSChildren evaluated for NF1 from 2009 to 2018 at Stanford University (n=78) were retrospectively reviewed and compared to healthy controls (n=100). All patients underwent diffusion-weighted (DWI) magnetic resonance imaging at 3T, and children with brain tumors were excluded. Using atlas-based DWI analyses, we assessed volume, median apparent diffusion coefficient (ADC), and cerebral blood flow in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. We also measured volume of the lateral ventricles. Multivariate analysis of covariance was used to test for differences between controls and NF1 patients, controlling for gender and age at time of imaging.RESULTSComparing NF1 to controls, we detected increased volume and decreased ASL cerebral blood flow in white matter and all subcortical and cortical structures except for brainstem volume. Median ADC was also increased in the thalamus, pallidum, hippocampus, and brainstem.CONCLUSIONSUsing a multi-parametric approach, we demonstrate quantitative measures of microstructural and physiologic changes of the NF1 brain. Atlas-based, quantitative MRI brain signatures may serve as biomarkers of neural development and further provide insight into associated cognitive dysfunction or risks for vasculopathy-related strokes in children with NF1.

Intracranial vascular feature changes in time of flight MR angiography in patients undergoing carotid revascularization surgery

PurposeTo characterize the intracranial vascular features extracted from time of flight (TOF) images and their changes from baseline to follow-up in patients undergoing carotid revascularization, using arterial spin labeling (ASL) cerebral blood flow (CBF) measurement as a reference. MethodsIn this retrospective study, brain TOF and ASL images of 99 subjects, acquired before, within 48 h, and/or 6 months after, carotid revascularization surgery were analyzed. TOF images were analyzed using a custom software (iCafe) to quantify intracranial vascular features, including total vessel length, total vessel volume, and number of branches. Mean whole-brain CBF was calculated from ASL images. ASL scans showing low ASL signal in the entire flow territory of an internal carotid artery (ICA), which may be caused by labeling failure, were excluded. Changes and correlations between time points were analyzed separately for TOF intracranial vascular features and ASL CBF. ResultsSimilar to ASL CBF, TOF vascular features (i.e. total vessel length, total vessel volume and number of branches) increased dramatically from baseline to post-surgery, then returned to a level slightly higher than the baseline in long-term follow-up (All P < 0.05). Correlation between time points was observed for all three TOF vascular features but not for ASL CBF. ConclusionIntracranial vascular features, including total vessel length, total vessel volume and number of branches, extracted from TOF images are useful in detecting brain blood flow changes induced by carotid revascularization surgery.

Age-related differences in cerebral blood flow and cortical thickness with an application to age prediction

Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In this study, T1-weighted structural magnetic resonance imaging and arterial spin labeling CBF images were acquired in 146 healthy participants across the adult life span. Sixty-eight cerebral cortex regions were segmented, and the cortical thickness and mean CBF were computed for each region. Linear regression with age was computed for each region and data type, and laterality and correlation matrices were computed. Sixteen predictive models were trained with the cortical thickness and CBF data alone as well as a combination of both data types. The age explained more variance in the cortical thickness data (average R2 of 0.21) than in the CBF data (average R2 of 0.09). All 16 models performed significantly better when combining both measurement types and using feature selection, and thus, we conclude that the inclusion of CBF data marginally improves age estimation.