Whole-brain histogram analysis and top 20% gray and white matter ratio of amyloid positron emission tomography: A comparison with the centiloid scale

Abstract Objective To compare whole-brain histogram analysis (WBHA) of amyloid-β (Aβ) positron emission tomography (PET) using several magnetic resonance imaging (MRI)-based brain extraction (brain extraction tool [BET]) methods, to evaluate a novel quantitative analysis method, namely the Top 20% Gray and White Matter Ratio (GW-ratio), to determine appropriate thresholds, and to evaluate diagnostic performance in comparison with the Centiloid scale (CL). Methods We analyzed structural MRI, 18 F-flutemetamol amyloid PET images, and dementia severity scores (Global Clinical Dementia Rating [G-CDR] and Mini-Mental State Examination [MMSE]) of 262 participants. For WBHA, BET was performed using structural MRI and three different BET software programs, namely High-Definition-BET (HD-BET), FMRIB Software Library (FSL), and Statistical Parametric Mapping (SPM). Skewness and mode-to-mean ratio (MMR) were measured using brain-extracted PET. The Top 20% Map was generated from SPM BET images, separated into gray and white matter voxels, and their ratio was calculated as the GW-ratio. The CL value was computed using structural MRI. Aβ-negativity or positivity was visually determined. Results Skewness from three BET methods was strongly negatively correlated with CL. Skewness (HD-BET) showed the strongest correlation (R = -0.9043). Moreover, the GW-ratio strongly correlated with CL (R = 0.8332), whereas MMR, particularly MMR (FSL) (R = 0.2112), showed poor correlation. All indicators significantly distinguished Aβ-negative from Aβ-positive visuals. CL had the highest area under the curve (AUC, 0.9959), followed by skewness (HD-BET) (0.9927), Top 20% GW-ratio (0.9872), and skewness (SPM) (0.9779), with no statistical difference between CL and skewness (HD-BET) ( P = 0.5763). Based on mean and SD values from 118 cognitively unimpaired (G-CDR = 0, MMSE ≥ 28) and visually Aβ-negative participants, 95% cut-off limits for Aβ-negative individuals without dementia symptoms were: CL ≤ 12.9, skewness (HD-BET) ≥ 0.1769, MMR (HD-BET) ≤ 0.9372, skewness (FSL) ≥ 0.1819, MMR (FSL) ≤ 1.9132, skewness (SPM) ≥ -0.0382, MMR (SPM) ≤ 1.1274, and GW-ratio ≤ 0.1079. Conclusion WBHA using MRI-based BET and GW-ratio showed strong correlations with CL and demonstrated a diagnostic performance comparable to that of CL.

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Journal
Annals of Nuclear Medicine
Published
2026-05-18
DOI
https://doi.org/10.1007/s12149-026-02218-9
Primary Topic
Dementia and Cognitive Impairment Research
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article
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article

Whole-brain histogram analysis and top 20% gray and white matter ratio of amyloid positron emission tomography: A comparison with the centiloid scale

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Annals of Nuclear Medicine
Dementia and Cognitive Impairment Research
article

Whole-brain histogram analysis and top 20% gray and white matter ratio of amyloid positron emission tomography: A comparison with the centiloid scale

Ayaka Nemoto, Yoshie Omachi, Shigeyasu Sugawara, Takashi Hanakawa, Hiroyasu Ikeno, Kazuaki Sajima, Masanori Sawamura, Jun Tazoe, Yosuke Taruno, Etsuro Nakanishi, Hideaki Takasumi, Harumasa Takano, Yuji Takahashi, Takeshi Nii, Tomohisa Okada, Atsushi Shima, Shiho Ubukata, Kentaro Akazawa, Yoko Nakano, Nozomu Matsuda, Mitsunari Abe, Fukiko Morii‐Kitani, Kyoji Okita, 福岡寛子, Shinya Seino, Kotaro Hattori, Yasutaka Fushimi, Emiya Koike, Kiyoaki Takeda, Hiroshi Hoshino, Yayoi Kurihara, Teruyuki Matsuoka, Atsuko Inoue, Nobukatsu Sawamoto, Fumitoshi Niwa, Noritaka Wakasugi, Ryo Yamakuni, Yusuke Sakato, Kasumi Hattori, Hiroki Togo, Haruhi Sakamaki‐Tsukita, Ikko Wada, Wataru Toda, Minoru Oto, Daisuke Kambe, Daisuke Goto, Takashi Kasai, Kazuaki Kanai, Kenji Yoshinaga, Toma Matsushima, Noriko Nishikawa, Yuta Terada, Anna Yamaki, Takashi Kanezawa, Yuhei Mori, Kazuko Kanno, Takashi Sakamoto, Mayumi Inoue, Koichi Kato, Toshiki Mizuno, Yasuhiro Hashimoto, Yoshiki Endo, Yuka Ueda, Hirooki Yabe, Yohei Aoshima, Tadashi Tsukamoto, Shizuko Sugou, Atsushi Sekiguchi, Sinobu Kawakakatsu, Hironobu Ishikawa, Shinichiro Mogi, Toshiya Murai, Hirofumi Sekino, Yuji Nakamoto, Ryosuke Takahashi, Nagara Tamaki, Jin Narumoto, Kenji Fukushima, Akira Nishida, Yuya Hagane, Hiroshi Hayashi, Tomoya Kotani, Kenji Hishikawa, Yohei Mukai, Masaki Kondo, Toshiki Nakahara, Naoto Kobayashi, Koji Furukawa, Katuyuki Kikori, Hiroshi Ito, Kei Yamada, Hodaka Yamakado, Kenji Yoshimura, Alzheimer’s disease Dimensional Neuroimaging Initiative (PADNI) Parkinson’s, Naoyuki Ukon, Shiro Ishii
article en

Abstract

Abstract Objective To compare whole-brain histogram analysis (WBHA) of amyloid-β (Aβ) positron emission tomography (PET) using several magnetic resonance imaging (MRI)-based brain extraction (brain extraction tool [BET]) methods, to evaluate a novel quantitative analysis method, namely the Top 20% Gray and White Matter Ratio (GW-ratio), to determine appropriate thresholds, and to evaluate diagnostic performance in comparison with the Centiloid scale (CL). Methods We analyzed structural MRI, 18 F-flutemetamol amyloid PET images, and dementia severity scores (Global Clinical Dementia Rating [G-CDR] and Mini-Mental State Examination [MMSE]) of 262 participants. For WBHA, BET was performed using structural MRI and three different BET software programs, namely High-Definition-BET (HD-BET), FMRIB Software Library (FSL), and Statistical Parametric Mapping (SPM). Skewness and mode-to-mean ratio (MMR) were measured using brain-extracted PET. The Top 20% Map was generated from SPM BET images, separated into gray and white matter voxels, and their ratio was calculated as the GW-ratio. The CL value was computed using structural MRI. Aβ-negativity or positivity was visually determined. Results Skewness from three BET methods was strongly negatively correlated with CL. Skewness (HD-BET) showed the strongest correlation (R = -0.9043). Moreover, the GW-ratio strongly correlated with CL (R = 0.8332), whereas MMR, particularly MMR (FSL) (R = 0.2112), showed poor correlation. All indicators significantly distinguished Aβ-negative from Aβ-positive visuals. CL had the highest area under the curve (AUC, 0.9959), followed by skewness (HD-BET) (0.9927), Top 20% GW-ratio (0.9872), and skewness (SPM) (0.9779), with no statistical difference between CL and skewness (HD-BET) ( P = 0.5763). Based on mean and SD values from 118 cognitively unimpaired (G-CDR = 0, MMSE ≥ 28) and visually Aβ-negative participants, 95% cut-off limits for Aβ-negative individuals without dementia symptoms were: CL ≤ 12.9, skewness (HD-BET) ≥ 0.1769, MMR (HD-BET) ≤ 0.9372, skewness (FSL) ≥ 0.1819, MMR (FSL) ≤ 1.9132, skewness (SPM) ≥ -0.0382, MMR (SPM) ≤ 1.1274, and GW-ratio ≤ 0.1079. Conclusion WBHA using MRI-based BET and GW-ratio showed strong correlations with CL and demonstrated a diagnostic performance comparable to that of CL.

Annals of Nuclear Medicine
Fukushima Medical University (JP), Kyoto University (JP), Kyoto Prefectural University of Medicine (JP), National Cancer Centre Japan (JP), Fukushima Medical University Hospital (JP)
Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science
Openalex Percentile: Top 6%
Dementia and Cognitive Impairment Research
DOIOpen Access PDFOpenAlex
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