title: New rapid, accurate T2quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients.
abstract: Quantitative T2mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38).
  
  
  
  The EMC algorithm uses Bloch simulations to model T2decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation.
  
  
  
  Compared to conventional exponential T2modeling, EMC fitting provided more accurate estimations of T2with less variance across scans, MRI systems, and healthy individuals. Thalamic T2was increased 8.5% in RRMS subjects (p< 0.001) and could be used to discriminate RRMS from healthy controls well (AUC = 0.913). Manual segmentation detected both statistically significant increases (corpus callosum & temporal stem) and decreases (posterior limb internal capsule) in T2associated with RRMS diagnosis (allp< 0.05). In healthy controls, we also observed statistically significant T2differences for different white and gray matter structures.
  
  
  
  The EMC algorithm precisely characterizes T2values, and is able to detect subtle T2changes in normal-appearing brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States; Center for Advanced Imaging Innovation and Research (CAI2R), New York, NY, United States.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Shepherd
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States; Center for Advanced Imaging Innovation and Research (CAI2R), New York, NY, United States.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Kirov
authors.affiliation: Department of Neurology & Multiple Sclerosis Comprehensive Care Center, New York University Langone School of Medicine, New York, NY, United States.
authors.forename: Erik
authors.initials: E
authors.lastname: Charlson
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Bruno
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States.
authors.forename: James
authors.initials: J
authors.lastname: Babb
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States; Center for Advanced Imaging Innovation and Research (CAI2R), New York, NY, United States.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Sodickson
authors.affiliation: Department of Radiology, New York University Langone School of Medicine, New York, NY, United States; Center for Advanced Imaging Innovation and Research (CAI2R), New York, NY, United States.
authors.forename: Noam
authors.initials: N
authors.lastname: Ben-Eliezer
mesh_terms: D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: AUC, area under the curve; B1 +,  transmit field; Biomarkers; Demyelination; EMC, echo modulation curve; FLAIR, fluid-attenuated inversion recovery; GM, gray matter; MPRAGE, magnetization-prepared rapid gradient-echo; MSE, multi-spin echo; MWF, myelin water fraction; Mesoscopic; Neurodegeneration; ROI, Region of Interest; RRMS, relapsing-remitting multiple sclerosis; Relaxation; SPACE, sampling perfection with application-optimized contrasts using different flip angle evolution; SSE, single spin echo; WM, white matter