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Objective <p>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).</p> Methods <p>We analyzed structural MRI, <sup>18</sup>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.</p> Results <p>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) (<i>P</i> = 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.</p> Conclusion <p>WBHA using MRI-based BET and GW-ratio showed strong correlations with CL and demonstrated a diagnostic performance comparable to that of CL.</p>

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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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  • 发表日期：

    2026年5月18日

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

摘要

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, 18F-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.