title: Use of T1-weighted/T2-weighted magnetic resonance ratio to elucidate changes due to amyloid β accumulation in cognitively normal subjects.
abstract: The ratio of signal intensity in T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) was recently proposed to enhance the sensitivity of detecting changes in disease-related signal intensity. The objective of this study was to test the effectiveness of T1w/T2w image ratios as an easily accessible biomarker for amyloid beta (Aβ) accumulation. We performed the T1w/T2w analysis in cognitively normal elderly individuals. We applied [11C] Pittsburgh Compound B (PiB)-PET to the same individuals, and Aβ deposition was quantified by its binding potential (PiB-BPND). The subjects were divided into low and high PiB-BPNDgroups, and group differences in regional T1w/T2w values were evaluated. In the regions where we found a significant group difference, we conducted a correlation analysis between regional T1w/T2w values and PiB-BPND. Subjects with high global cortical PiB-BPNDshowed a significantly higher regional T1w/T2w ratio in the frontal cortex and anterior cingulate cortex.We found a significant positive relationship between the regional T1w/T2w ratio and Aβ accumulation. Moreover, with a T1w/T2w ratio of 0.55 in the medial frontal regions, we correctly discriminated subjects with high PiB-BPNDfrom the entire subject population with a sensitivity of 84.6% and specificity of 80.0%. Our results indicate that early Aβ-induced pathological changes can be detected using the T1w/T2w ratio on MRI. We believe that the T1w/T2w ratio is a prospective stable biological marker of early Aβ accumulation in cognitively normal individuals. The availability of such an accessible marker would improve the efficiency of clinical trials focusing on the initial disease stages by reducing the number of subjects who require screening by Aβ-PET scan or lumbar puncture.
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Japan; Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.affiliation: Department of Neuropsychiatry, Osaka University Medical School, Suita, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kazui
authors.affiliation: Department of Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Morita
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Kajimoto
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Nakagawara
authors.affiliation: Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D013844:Thiazoles
keywords: 11C–labeled Pittsburgh Compound B ([11C]PiB); AD, Alzheimer's disease; Alzheimer's disease (AD); Amyloid-β (Aβ); Aβ, amyloid beta; BP, binding potential; CSF, cerebrospinal fluid; FWHM, full-width at half maximum; MRI, magnetic resonance imaging; PET, positron emission tomography; PiB, Pittsburgh Compound B; PiB-BPND, PiB-BP estimates relative to non-displaceable (ND) binding; Positron emission tomography (PET); ROC, receiver operating characteristic; T1-weighted/T2-weighted magnetic resonance ratio images; T1w, T1-weighted; T2w, T2-weighted; VOI, volumes of interest