title: Fast whole-brain three-dimensional macromolecular proton fraction mapping in multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the clinical utility of fast whole-brain macromolecular proton fraction ( MPF macromolecular proton fraction ) mapping in multiple sclerosis ( MS multiple sclerosis ) and compare MPF macromolecular proton fraction with established quantitative magnetic resonance (MR) imaging measures of tissue damage including magnetization transfer ( MT magnetization transfer ) ratio and relaxation rate (R1).
  
  
  METHODS
  In this institutional review board-approved and HIPAA-compliant study, 14 healthy control participants, 18 relapsing-remitting MS multiple sclerosis ( RRMS relaxing-remitting MS ) patients, and 12 secondary progressive MS multiple sclerosis ( SPMS secondary progressive MS ) patients provided written informed consent and underwent 3-T MR imaging. Three-dimensional MPF macromolecular proton fraction maps were reconstructed from MT magnetization transfer -weighted images and R1 maps by the single-point method. Mean MPF macromolecular proton fraction , R1, and MT magnetization transfer ratio in normal-appearing white matter ( WM white matter ), gray matter ( GM gray matter ), and lesions were compared between subject groups by using analysis of variance. Correlations (Pearson r) between imaging data and clinical scores (Expanded Disability Status Scale [EDSS] and MS multiple sclerosis Functional Composite [ MSFC MS functional composite ]) were compared by using Hotelling-Williams test.
  
  
  RESULTS
  RRMS relaxing-remitting MS patients had lower WM white matter and GM gray matter MPF macromolecular proton fraction than controls, with percentage decreases of 6.5% (P < .005) and 5.4% (P < .05). MPF macromolecular proton fraction in SPMS secondary progressive MS was reduced relative to RRMS relaxing-remitting MS in WM white matter , GM gray matter , and lesions by 6.4% (P < .005), 13.4% (P < .005), and 11.7% (P < .05), respectively. EDSS Expanded Disability Status Scale and MSFC MS functional composite demonstrated strongest correlations with MPF macromolecular proton fraction in GM gray matter (r = -0.74 and 0.81; P < .001) followed by WM white matter (r = -0.57 and 0.72; P < .01) and lesions (r = -0.42 and 0.50; P < .05). R1 and MT magnetization transfer ratio in all tissues were significantly less correlated with clinical scores than GM gray matter MPF macromolecular proton fraction (P < .05).
  
  
  CONCLUSIONS
  MPF macromolecular proton fraction mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of GM gray matter damage in MS multiple sclerosis . MPF macromolecular proton fraction outperforms MT magnetization transfer ratio and R1 in detection of MS multiple sclerosis -related tissue changes.
authors.affiliation: From the Department of Radiology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195 (V.L.Y., K.R.M.); Multiple Sclerosis Center (J.D.B., P.R., A.M., P.Q., B.G., L.K.J.H.) and Department of Radiology (B.P.K.), Swedish Neuroscience Institute, Seattle, Wash; and Department of Radiology, University of Wisconsin, Madison, Wis (A.S.).
authors.forename: Vasily L
authors.initials: VL
authors.lastname: Yarnykh
authors.forename: James D
authors.initials: JD
authors.lastname: Bowen
authors.forename: Alexey
authors.initials: A
authors.lastname: Samsonov
authors.forename: Pavle
authors.initials: P
authors.lastname: Repovic
authors.forename: Angeli
authors.initials: A
authors.lastname: Mayadev
authors.forename: Peiqing
authors.initials: P
authors.lastname: Qian
authors.forename: Beena
authors.initials: B
authors.lastname: Gangadharan
authors.forename: Bart P
authors.initials: BP
authors.lastname: Keogh
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Maravilla
authors.forename: Lily K
authors.initials: LK
authors.lastname: Jung Henson
mesh_terms: D000328:Adult; D000368:Aged; D001931:Brain Mapping / Q000379:methods*; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D011446:Prospective Studies; D011522:Protons
chemical_list: D011522:Protons