Biao Xiang1, Matthew R Brier2, Manasa Kanthamneni3, Jie Wen1, Abraham Z Snyder4, Dmitriy A Yablonskiy1, Anne H Cross2. 1. Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA. 2. Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA. 3. Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA/School of Medicine, St. George's University, St. George, Grenada. 4. Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA/Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Abstract
BACKGROUND: Imaging biomarkers of progressive multiple sclerosis (MS) are needed. Quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) evaluates microstructural tissue damage in MS. OBJECTIVE: To evaluate qGRE-derived R2t* as an imaging biomarker of MS progression compared with atrophy and lesion burden. METHODS: Twenty-three non-relapsing progressive MS (PMS), 22 relapsing-remitting MS (RRMS), and 18 healthy control participants underwent standard MS physical and cognitive neurological assessments and imaging with qGRE, FLAIR, and MPRAGE at 3T. PMS subjects were tested clinically and imaged every 9 months over 45 months. Imaging measures included lesion burden, atrophy, and R2t* in cortical gray matter (GM), deep GM, and normal-appearing white matter (NAWM). Longitudinal analysis of clinical performance and imaging biomarkers in PMS subjects was conducted via linear models with subject as repeated, within-subject factor. Relationship between imaging biomarkers and clinical scores was assessed by Spearman rank correlation. RESULTS: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression (N = 13) showed faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group (N = 10). Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. CONCLUSION: qGRE-derived R2t* is a potential imaging biomarker of MS progression.
BACKGROUND: Imaging biomarkers of progressive multiple sclerosis (MS) are needed. Quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) evaluates microstructural tissue damage in MS. OBJECTIVE: To evaluate qGRE-derived R2t* as an imaging biomarker of MS progression compared with atrophy and lesion burden. METHODS: Twenty-three non-relapsing progressive MS (PMS), 22 relapsing-remitting MS (RRMS), and 18 healthy control participants underwent standard MS physical and cognitive neurological assessments and imaging with qGRE, FLAIR, and MPRAGE at 3T. PMS subjects were tested clinically and imaged every 9 months over 45 months. Imaging measures included lesion burden, atrophy, and R2t* in cortical gray matter (GM), deep GM, and normal-appearing white matter (NAWM). Longitudinal analysis of clinical performance and imaging biomarkers in PMS subjects was conducted via linear models with subject as repeated, within-subject factor. Relationship between imaging biomarkers and clinical scores was assessed by Spearman rank correlation. RESULTS: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression (N = 13) showed faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group (N = 10). Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. CONCLUSION: qGRE-derived R2t* is a potential imaging biomarker of MS progression.
Authors: Robert J Fox; Christopher S Coffey; Robin Conwit; Merit E Cudkowicz; Trevis Gleason; Andrew Goodman; Eric C Klawiter; Kazuko Matsuda; Michelle McGovern; Robert T Naismith; Akshata Ashokkumar; Janel Barnes; Dixie Ecklund; Elizabeth Klingner; Maxine Koepp; Jeffrey D Long; Sneha Natarajan; Brenda Thornell; Jon Yankey; Robert A Bermel; Josef P Debbins; Xuemei Huang; Patricia Jagodnik; Mark J Lowe; Kunio Nakamura; Sridar Narayanan; Ken E Sakaie; Bhaskar Thoomukuntla; Xiaopeng Zhou; Stephen Krieger; Enrique Alvarez; Michelle Apperson; Khurram Bashir; Bruce A Cohen; Patricia K Coyle; Silvia Delgado; L Dana Dewitt; Angela Flores; Barbara S Giesser; Myla D Goldman; Burk Jubelt; Neil Lava; Sharon G Lynch; Harold Moses; Daniel Ontaneda; Jai S Perumal; Michael Racke; Pavle Repovic; Claire S Riley; Christopher Severson; Shlomo Shinnar; Valerie Suski; Bianca Weinstock-Guttman; Vijayshree Yadav; Aram Zabeti Journal: N Engl J Med Date: 2018-08-30 Impact factor: 91.245
Authors: Jiwon Oh; Daniel Ontaneda; Christina Azevedo; Eric C Klawiter; Martina Absinta; Douglas L Arnold; Rohit Bakshi; Peter A Calabresi; Ciprian Crainiceanu; Blake Dewey; Leorah Freeman; Susan Gauthier; Roland Henry; Mathilde Inglese; Shannon Kolind; David K B Li; Caterina Mainero; Ravi S Menon; Govind Nair; Sridar Narayanan; Flavia Nelson; Daniel Pelletier; Alexander Rauscher; William Rooney; Pascal Sati; Daniel Schwartz; Russell T Shinohara; Ian Tagge; Anthony Traboulsee; Yi Wang; Youngjin Yoo; Tarek Yousry; Yunyan Zhang; Nancy L Sicotte; Daniel S Reich Journal: Neurology Date: 2019-02-20 Impact factor: 9.910
Authors: Tammie L S Benzinger; Robert T Naismith; Matthew R Brier; Abraham Z Snyder; Aaron Tanenbaum; Richard A Rudick; Elizabeth Fisher; Stephen Jones; Joshua S Shimony; Anne H Cross Journal: Ann Clin Transl Neurol Date: 2021-05-04 Impact factor: 4.511
Authors: Biao Xiang; Jie Wen; Hsiang-Chih Lu; Robert E Schmidt; Dmitriy A Yablonskiy; Anne H Cross Journal: Ann Clin Transl Neurol Date: 2020-05-04 Impact factor: 4.511