Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity

Ji Eun Park; Jessica Yun; Sang Joon Kim; Woo Hyun Shim; Jungsu S Oh; Minyoung Oh; Jee Hoon Roh; Sang Won Seo; Seung Jun Oh; Jae Seung Kim

doi:10.1371/journal.pone.0226265

Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity

PLoS One. 2019 Dec 13;14(12):e0226265. doi: 10.1371/journal.pone.0226265. eCollection 2019.

Authors

Affiliations

¹ Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
² Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
³ Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
⁴ Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro, Kangnam-ku, Seoul, South Korea.

Abstract

Purpose: To assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer's disease (AD).

Materials and methods: Sixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson's correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity.

Results: No significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = -0.576-0.781) than the MCI group (r = 0.368-0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = -0.494, P = .012) in the β-amyloid PET-positive group.

Conclusions: Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / pathology*
Amyloid / chemistry*
Aniline Compounds / chemistry
Case-Control Studies
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / pathology*
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / pathology*
Female
Follow-Up Studies
Humans
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Positron-Emission Tomography / methods*
Prognosis
Prospective Studies
Severity of Illness Index*

Substances

Amyloid
Aniline Compounds

Associated data

ClinicalTrials.gov/NCT02656498

Grants and funding

This study was supported by grant HI14C2768 and HR18C2383 from the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute, funded by the Ministry of Health &Welfare, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.