The value of arterial spin labelling perfusion MRI in brain age prediction.

Current structural MRI-based brain age estimates and their difference from chronological age-the brain age gap (BAG)-are limited to late-stage pathological brain-tissue changes. The addition of physiological MRI features may detect early-stage pathological brain alterations and improve brain age prediction. This study investigated the optimal combination of structural and physiological arterial spin labelling (ASL) image features and algorithms. Healthy participants (n = 341, age 59.7 ± 14.8 years) were scanned at baseline and after 1.7 ± 0.5 years follow-up (n = 248, mean age 62.4 ± 13.3 years). From 3 T MRI, structural (T1w and FLAIR) volumetric ROI and physiological (ASL) cerebral blood flow (CBF) and spatial coefficient of variation ROI features were constructed. Multiple combinations of features and machine learning algorithms were evaluated using the Mean Absolute Error (MAE). From the best model, longitudinal BAG repeatability and feature importance were assessed. The ElasticNetCV algorithm using T1w + FLAIR+ASL performed best (MAE = 5.0 ± 0.3 years), and better compared with using T1w + FLAIR (MAE = 6.0 ± 0.4 years, p < .01). The three most important features were, in descending order, GM CBF, GM/ICV, and WM CBF. Average baseline and follow-up BAGs were similar (-1.5 ± 6.3 and - 1.1 ± 6.4 years respectively, ICC = 0.85, 95% CI: 0.8-0.9, p = .16). The addition of ASL features to structural brain age, combined with the ElasticNetCV algorithm, improved brain age prediction the most, and performed best in a cross-sectional and repeatability comparison. These findings encourage future studies to explore the value of ASL in brain age in various pathologies.

Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults.

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, 'CO2 in air' and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, 'CO2 in air' and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for 'CO2 in air' and carbogen, respectively). CMRO2 decreased for 'CO2 in air' (-13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that 'CO2 in air' is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

A Beginner's Guide to Arterial Spin Labeling (ASL) Image Processing.

Arterial spin labeling (ASL) is a non-invasive and cost-effective MRI technique for brain perfusion measurements. While it has developed into a robust technique for scientific and clinical use, its image processing can still be daunting. The 2019 Ann Arbor ISMRM ASL working group established that education is one of the main areas that can accelerate the use of ASL in research and clinical practice. Specifically, the post-acquisition processing of ASL images and their preparation for region-of-interest or voxel-wise statistical analyses is a topic that has not yet received much educational attention. This educational review is aimed at those with an interest in ASL image processing and analysis. We provide summaries of all typical ASL processing steps on both single-subject and group levels. The readers are assumed to have a basic understanding of cerebral perfusion (patho) physiology; a basic level of programming or image analysis is not required. Starting with an introduction of the physiology and MRI technique behind ASL, and how they interact with the image processing, we present an overview of processing pipelines and explain the specific ASL processing steps. Example video and image illustrations of ASL studies of different cases, as well as model calculations, help the reader develop an understanding of which processing steps to check for their own analyses. Some of the educational content can be extrapolated to the processing of other MRI data. We anticipate that this educational review will help accelerate the application of ASL MRI for clinical brain research.

The Open-Access European Prevention of Alzheimer's Dementia (EPAD) MRI dataset and processing workflow.

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI preprocessing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses.