An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with 18F-PM-PBB3 (18F-APN-1607)
An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with 18F-PM-PBB3 (18F-APN-1607)
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DOI：
10.1016/j.neuroimage.2022.119763
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发表时间：
2022-02
期刊：
影响因子：
5.7
通讯作者：
K. Tagai;Y. Ikoma;H. Endo;O. Debnath;C. Seki;K. Matsuoka;H. Matsumoto;M. Oya;K. Hirata;H. Shinotoh;K. Takahata;S. Kurose;Yasunori Sano;M. Ono;H. Shimada;K. Kawamura;Z. Ming-rong;Y. Takado;M. Higuchi
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作者：
K. Tagai;Y. Ikoma;H. Endo;O. Debnath;C. Seki;K. Matsuoka;H. Matsumoto;M. Oya;K. Hirata;H. Shinotoh;K. Takahata;S. Kurose;Yasunori Sano;M. Ono;H. Shimada;K. Kawamura;Z. Ming-rong;Y. Takado;M. Higuchi
使用18F-PM-PBB3(18F-APN-1607，18F-Florzolotau)的正电子发射断层扫描(PET)可以高对比度检测各种神经退行性痴呆患者的tau沉积，包括阿尔茨海默病(AD)和额颞叶变性(FTLD)。一种用于定量靶区放射性配基结合的简化方法是使用小脑作为参照物(CB-REF)，假设小脑有最小的tau病变。这种方法在AD中通常有效，而以进行性核上性麻痹(PSP)为例的FTLD疾病的特点是小脑中偶尔有tau积聚，阻碍了CB-REF的应用。本研究旨在建立一种在AD和非AD患者脑18F-PM-PBB3-PET图像上确定参考组织的最佳方法。我们开发了一种新的算法来从灰质(GM-REF)或白质(WM-REF)中提取包含tau沉积的可能性较低的参考体素，方法是通过对放射配基保留的个体体素方向直方图进行双峰拟合，并将其应用于来自年龄匹配的40名健康对照组(HCS)和23名CE、40名PSP和其他5名tau阳性FTLD患者的18F-PM-PBB3-PET数据。在注射后90-110分钟采集的PET图像被平均并共同配准到相应的磁共振成像空间。随后，我们生成了分别由CB-REF、GM-REF和WM-REF估计的标准化摄取值比(SUVR)图像，并比较了它们的诊断性能。GM-REF和WM-REF在HCS中覆盖了广泛的区域，并且在AD和PSP患者中没有位于已知承担高tau负荷的区域的体素。然而，WM-REF中的放射性配基保留率显示出与年龄相关的下降。GM-REF不受年龄的影响，在可疑和确诊的FTLD患者中，GM-REF提供了比CB-RF更高对比度的SUVR图像。这里优化的确定参考组织的方法提高了18F-PM-PBB3-PET测量各种神经退行性疾病的tau负荷的准确性。
Positron emission tomography (PET) with18F-PM-PBB3 (18F-APN-1607,18F-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 on18F-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 to18F-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 of18F-PM-PBB3-PET measurements of tau burdens in a wide range of neurodegenerative illnesses.