Tagai Kenji, Ikoma Yoko, Endo Hironobu, Debnath Oiendrila Bhowmik, Seki Chie, Matsuoka Kiwamu, Matsumoto Hideki, Oya Masaki, Hirata Kosei, Shinotoh Hitoshi, Takahata Keisuke, Kurose Shin, Sano Yasunori, Ono Maiko, Shimada Hitoshi, Kawamura Kazunori, Zhang Ming-Rong, Takado Yuhei, Higuchi Makoto
Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Institute for Quantum Medical Science, Chiba 263-8555, Japan; Department of Psychiatry, The Jikei University of Medicine, Tokyo 105-8461, Japan.
Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Institute for Quantum Medical Science, Chiba 263-8555, Japan.
Neuroimage. 2022 Dec 1;264:119763. doi: 10.1016/j.neuroimage.2022.119763. Epub 2022 Nov 24.
Positron emission tomography (PET) with F-PM-PBB3 (F-APN-1607, F-Florzolotau) enables high-contrast detection of tau depositions in various neurodegenerative dementias, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). A simplified method for quantifying radioligand binding in target regions is to employ the cerebellum as a reference (CB-ref) on the assumption that the cerebellum has minimal tau pathologies. This procedure is typically valid in AD, while FTLD disorders exemplified by progressive supranuclear palsy (PSP) are characterized by occasional tau accumulations in the cerebellum, hampering the application of CB-ref. The present study aimed to establish an optimal method for defining reference tissues on F-PM-PBB3-PET images of AD and non-AD tauopathy brains. We developed a new algorithm to extract reference voxels with a low likelihood of containing tau deposits from gray matter (GM-ref) or white matter (WM-ref) by a bimodal fit to an individual, voxel-wise histogram of the radioligand retentions and applied it to F-PM-PBB3-PET data obtained from age-matched 40 healthy controls (HCs) and 23 CE, 40 PSP, and five other tau-positive FTLD patients. PET images acquired at 90-110 min after injection were averaged and co-registered to corresponding magnetic resonance imaging space. Subsequently, we generated standardized uptake value ratio (SUVR) images estimated by CB-ref, GM-ref and WM-ref, respectively, and then compared the diagnostic performances. GM-ref and WM-ref covered a broad area in HCs and were free of voxels located in regions known to bear high tau burdens in AD and PSP patients. However, radioligand retentions in WM-ref exhibited age-related declines. GM-ref was unaffected by aging and provided SUVR images with higher contrast than CB-ref in FTLD patients with suspected and confirmed corticobasal degeneration. The methodology for determining reference tissues as optimized here improves the accuracy of F-PM-PBB3-PET measurements of tau burdens in a wide range of neurodegenerative illnesses.
使用F-PM-PBB3（F-APN-1607，F-Florzolotau）的正电子发射断层扫描（PET）能够高对比度检测各种神经退行性痴呆中的tau蛋白沉积，包括阿尔茨海默病（AD）和额颞叶变性（FTLD）。一种在目标区域量化放射性配体结合的简化方法是，假设小脑的tau蛋白病变最少，将小脑用作参考（CB-ref）。该方法在AD中通常是有效的，而以进行性核上性麻痹（PSP）为代表的FTLD疾病的特征是小脑中偶尔会有tau蛋白积聚，这妨碍了CB-ref的应用。本研究旨在建立一种在AD和非AD tau蛋白病脑的F-PM-PBB3-PET图像上定义参考组织的最佳方法。我们开发了一种新算法，通过对放射性配体滞留的个体体素直方图进行双峰拟合，从灰质（GM-ref）或白质（WM-ref）中提取含有tau蛋白沉积可能性较低的参考体素，并将其应用于从年龄匹配的40名健康对照（HC）以及23名皮质基底节变性（CBD）、40名PSP和5名其他tau蛋白阳性FTLD患者获得的F-PM-PBB3-PET数据。在注射后90 - 110分钟采集的PET图像进行平均，并与相应的磁共振成像空间进行配准。随后，我们分别生成了由CB-ref、GM-ref和WM-ref估计的标准化摄取值比（SUVR）图像，然后比较了诊断性能。GM-ref和WM-ref在HC中覆盖了广泛区域，并且没有位于AD和PSP患者中已知具有高tau蛋白负荷区域的体素。然而，WM-ref中的放射性配体滞留表现出与年龄相关的下降。GM-ref不受衰老影响，并且在疑似和确诊为皮质基底节变性的FTLD患者中提供了比CB-ref对比度更高的SUVR图像。这里优化的确定参考组织的方法提高了在广泛的神经退行性疾病中F-PM-PBB3-PET测量tau蛋白负荷的准确性。
