Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge
Peiying Liu,
Dengrong Jiang,
Marilyn Albert,
Christopher E. Bauer,
Arvind Caprihan,
Brian T. Gold,
Steven M. Greenberg,
Karl G. Helmer,
Kay Jann,
Gregory Jicha,
Pavel Rodriguez,
Claudia L. Satizabal,
Sudha Seshadri,
Herpreet Singh,
Jeffrey F. Thompson,
Danny J.J. Wang,
Hanzhang Lu
Affiliations
Peiying Liu
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Dengrong Jiang
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Marilyn Albert
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Christopher E. Bauer
Department of Neuroscience, University of Kentucky, Lexington, KY, USA
Arvind Caprihan
The Mind Research Network, Albuquerque, NM, USA
Brian T. Gold
Department of Neuroscience, University of Kentucky, Lexington, KY, USA
Steven M. Greenberg
Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
Karl G. Helmer
Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
Kay Jann
Laboratory of Functional MRI Technology, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Gregory Jicha
Department of Neurology, University of Kentucky, Lexington, KY, USA
Pavel Rodriguez
Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA
Claudia L. Satizabal
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA
Sudha Seshadri
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA
Herpreet Singh
Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
Jeffrey F. Thompson
Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Danny J.J. Wang
Laboratory of Functional MRI Technology, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Hanzhang Lu
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore 21287, USA; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, 21205, USA; Corresponding author at: Department of Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Park 322, Baltimore, MD, 21287, USA.
Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate the reliability of CO2-CVR quantification in three studies. First, the inter-rater reliability of CO2-CVR data processing was evaluated by having raters from 5 MarkVCID sites process the same 30 CVR datasets using a cloud-based CVR data processing pipeline. Second, the inter-scanner reproducibility of CO2-CVR quantification was assessed in 10 young subjects across two scanners of different vendors. Third, test-retest repeatability was evaluated in 20 elderly subjects from 4 sites with a scan interval of less than 2 weeks. In all studies, the CO2 CVR measurements were performed using the fixed inspiration method, where the subjects wore a nose clip and a mouthpiece and breathed room air and 5% CO2 air contained in a Douglas bag alternatively through their mouth. The results showed that the inter-rater CoV of CVR processing was 0.08 ± 0.08% for whole-brain CVR values and ranged from 0.16% to 0.88% in major brain regions, with ICC of absolute agreement above 0.9959 for all brain regions. Inter-scanner CoV was found to be 6.90 ± 5.08% for whole-brain CVR values, and ranged from 4.69% to 12.71% in major brain regions, which are comparable to intra-session CoVs obtained from the same scanners on the same day. ICC of consistency between the two scanners was 0.8498 for whole-brain CVR and ranged from 0.8052 to 0.9185 across major brain regions. In the test-retest evaluation, test-retest CoV across different days was found to be 18.29 ± 17.12% for whole-brain CVR values, and ranged from 16.58% to 19.52% in major brain regions, with ICC of absolute agreement ranged from 0.6480 to 0.7785. These results demonstrated good inter-rater, inter-scanner, and test-retest reliability in healthy volunteers, and suggested that CO2-CVR has suitable instrumental properties for use as an imaging biomarker of cerebrovascular function in multi-site and longitudinal observational studies and clinical trials.
