While imaging studies are widely used in clinical practice and research, the number of neuroimaging- based biomarkers is small. For example, in clinical trials of immunomodulatory therapies for MS, the only commonly used imaging biomarkers are the total lesion volume and the number of new and en- hancing lesions. These biomarkers are essential, but do not capture the recovery process of lesions, which is thought to decline in more severe, progressive disease. The partial or complete recovery of lesions may depend both on the ability of the brain to heal and on external factors, such as treat- ment or environmental and behavioral exposures. In this proposal we take the natural next step of proposing imaging biomarkers for MS based on the formation and change of lesions as observed on multi-sequence structural MRIs. To solve this problem we propose to address several general method- ological problems: 1) develop models and methods for the longitudinal analysis of several images of the same brain; 2) identify and estimate the length of history that is necessary to estimate recovery; 3) study the association with known biomarkers of the disease (in this case total volume and number of new and enhancing lesions); 4) develop methods that are robust to changes in imaging protocols that inevitably arise in longitudinal neuroimaging studies; and 5) develop the computational tools that allow for sophisticated methods to be implemented seamlessly in practice. While our scienti?c problem is focused, the proposed statistical methods are general and can be applied to a wide variety of longitu- dinal neuroimaging studies. For example, there are many ongoing longitudinal neuroimaging studies, including the ADNI, AIBL, HBC, and MISTIE, where our methods could be used to study subtle or large changes in lesions or in white and gray matter intensities.

Public Health Relevance

. The project provides statistical analysis methods for quanti?cation of the evolution in the intensity of brain lesions on multi-sequence Magnetic Resonance Imaging (MRI). Methods are motivated by the need to develop new neuroimaging-based biomarkers for multiple sclerosis (MS), but can be applied to other types of brain diseases including stroke, Alzheimer disease, and cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS060910-11
Application #
9635802
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gnadt, James W
Project Start
2009-01-01
Project End
2022-02-28
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
11
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Dworkin, J D; Sati, P; Solomon, A et al. (2018) Automated Integration of Multimodal MRI for the Probabilistic Detection of the Central Vein Sign in White Matter Lesions. AJNR Am J Neuroradiol 39:1806-1813
Valcarcel, Alessandra M; Linn, Kristin A; Vandekar, Simon N et al. (2018) MIMoSA: An Automated Method for Intermodal Segmentation Analysis of Multiple Sclerosis Brain Lesions. J Neuroimaging 28:389-398
Valcarcel, Alessandra M; Linn, Kristin A; Khalid, Fariha et al. (2018) A dual modeling approach to automatic segmentation of cerebral T2 hyperintensities and T1 black holes in multiple sclerosis. Neuroimage Clin 20:1211-1221
Dworkin, Jordan D; Shinohara, Russell T; Bassett, Danielle S (2018) The landscape of NeuroImage-ing research. Neuroimage 183:872-883
Reardon, P K; Seidlitz, Jakob; Vandekar, Simon et al. (2018) Normative brain size variation and brain shape diversity in humans. Science 360:1222-1227
Bai, Jiawei; Sun, Yifei; Schrack, Jennifer A et al. (2018) A two-stage model for wearable device data. Biometrics 74:744-752
Alexander-Bloch, Aaron F; Shou, Haochang; Liu, Siyuan et al. (2018) On testing for spatial correspondence between maps of human brain structure and function. Neuroimage 178:540-551
Yu, Meichen; Linn, Kristin A; Cook, Philip A et al. (2018) Statistical harmonization corrects site effects in functional connectivity measurements from multi-site fMRI data. Hum Brain Mapp 39:4213-4227
Leroux, Andrew; Xiao, Luo; Crainiceanu, Ciprian et al. (2018) Dynamic prediction in functional concurrent regression with an application to child growth. Stat Med 37:1376-1388
Muschelli, John; Sweeney, Elizabeth; Crainiceanu, Ciprian M (2018) freesurfer: Connecting the Freesurfer software with R. F1000Res 7:599

Showing the most recent 10 out of 102 publications