Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
Division of Neurology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
EJNMMI Res. 2016 Dec;6(1):24. doi: 10.1186/s13550-016-0182-y. Epub 2016 Mar 12.
Quantitative in vivo imaging of tau pathologies potentially improves diagnostic accuracy of neurodegenerative tauopathies and would facilitate evaluation of disease-modifying drugs targeting tau lesions in these diseases. Tau pathology can be quantified by reference tissue models without arterial blood sampling when reference tissue devoid of target binding sites is available. The cerebellar cortex has been used as a reference region in analyses of tau positron emission tomography (PET) data in Alzheimer's disease (AD). However, in a significant subset of tauopathies such as progressive supranuclear palsy and corticobasal degeneration, tau accumulation may occur in diverse brain regions including the cerebellar cortex. This hampers selection of a distinctive reference region lacking binding sites for a tau PET ligand. The purpose of this study was to develop a new method to quantify specific binding of a PET radioligand, (11)C-PBB3, to tau deposits using reference voxels extracted from cortical gray matter, which have a low likelihood of containing tau accumulations.
We reanalyzed (11)C-PBB3 PET data of seven mild AD patients (ADs) and seven elderly healthy control subjects (HCs) acquired in a previous study. As a standard method, parametric images of binding potential ([Formula: see text]) were initially generated using reference tissue manually defined on the cerebellar cortex. We then constructed a frequency histogram of [Formula: see text] values in these parametric images and selected cortical gray matter voxels contained in a certain range of the histogram with a low likelihood of having (11)C-PBB3 binding sites. Finally, these reference voxels were used for generating new [Formula: see text] parametric images.
Reference tissue voxels defined by the histogram analysis spread throughout the cortical gray matter of AD and HC brains. The [Formula: see text] values determined by our new method correlated very well with those estimated by the standard method (r (2) = 0.94), although the binding estimates by the current method were slightly higher by ~0.14 than those by the standard method.
We developed and validated a new method enabling quantification of tau lesions that can accumulate in the cerebellum and other extensive brain areas. This method may be applicable to all tauopathy subtypes and various tau PET ligands besides (11)C-PBB3.
The number is UMIN000009052.
定量活体成像 tau 病理学可能会提高神经退行性 tau 病的诊断准确性，并有助于评估针对这些疾病中 tau 病变的疾病修饰药物。当不存在靶结合位点的参考组织时，可以通过参考组织模型来定量 tau 病理学，而无需进行动脉血采样。小脑皮层已被用于分析阿尔茨海默病（AD）中 tau 正电子发射断层扫描（PET）数据。然而，在包括进行性核上性麻痹和皮质基底节变性在内的 tau 病的一个重要亚组中，tau 可能会在包括小脑皮层在内的不同脑区积累。这阻碍了对缺乏 tau PET 配体结合位点的独特参考区域的选择。本研究的目的是开发一种新方法，使用皮质灰质提取的参考体素来定量 PET 放射性配体（11）C-PBB3 与 tau 沉积物的特异性结合，该方法不太可能包含 tau 积累。
我们重新分析了先前研究中 7 名轻度 AD 患者（AD）和 7 名老年健康对照者（HC）的（11）C-PBB3 PET 数据。作为标准方法，最初使用手动定义在小脑皮层上的参考组织生成结合潜能（BP）的参数图像。然后，我们构建了这些参数图像中 BP 值的频率直方图，并选择了直方图中具有低（11）C-PBB3 结合位点可能性的皮质灰质体素。最后，使用这些参考体素来生成新的 BP 参数图像。
通过直方图分析定义的参考组织体素分布在 AD 和 HC 大脑的皮质灰质中。我们的新方法确定的 BP 值与标准方法非常吻合（r2=0.94），尽管当前方法的结合估计值比标准方法高约 0.14。
我们开发并验证了一种新方法，可定量测定可能在小脑和其他广泛脑区积累的 tau 病变。该方法可能适用于除（11）C-PBB3 以外的所有 tau 病亚型和各种 tau PET 配体。
编号为 UMIN000009052。
