Li Zekun, Benabdallah Nadia, Laforest Richard, Wahl Richard L, Thorek Daniel L J, Jha Abhinav K
ArXiv. 2024 Jul 1:arXiv:2305.17117v4.
Thorium-227-based alpha-particle radiopharmaceutical therapies ({\alpha}-RPTs) are being investigated in several clinical and pre-clinical studies. After administration, Thorium-227 decays to Radium-223, another alpha-particle-emitting isotope, which redistributes within the patient. Reliable dose quantification of both Thorium-227 and Radium-223 is clinically important, and SPECT may perform this quantification as these isotopes also emit X- and gamma-ray photons. However, reliable quantification is challenged by the orders-of-magnitude lower activity compared to conventional SPECT, resulting in a very low number of detected counts, the presence of multiple photopeaks, substantial overlap in the emission spectra of these isotopes, and the image-degrading effects in SPECT. To address these issues, we propose a multiple-energy-window projection-domain quantification (MEW-PDQ) method that jointly estimates the regional activity uptake of both Thorium-227 and Radium-223 directly using the SPECT projection from multiple energy windows. We evaluated the method with realistic simulation studies using anthropomorphic digital phantoms, in the context of imaging patients with bone metastases of prostate cancer and treated with Thorium-227-based {\alpha}-RPTs. The proposed method yielded reliable (accurate and precise) regional uptake estimates of both isotopes and outperformed state-of-the-art methods across different lesion sizes and contrasts, in a virtual imaging trial, as well as with moderate levels of intra-regional heterogeneous uptake and with moderate inaccuracies in the definitions of the support of various regions. Additionally, we demonstrated the effectiveness of using multiple energy windows and the variance of the estimated uptake using the proposed method approached the Cram'er-Rao-lower-bound-defined theoretical limit.
基于钍 - 227的α粒子放射性药物疗法(α - RPTs)正在多项临床和临床前研究中进行探索。给药后,钍 - 227衰变为镭 - 223,另一种发射α粒子的同位素,它会在患者体内重新分布。对钍 - 227和镭 - 223进行可靠的剂量定量在临床上具有重要意义,并且单光子发射计算机断层扫描(SPECT)可以进行这种定量,因为这些同位素也会发射X射线和γ射线光子。然而,与传统SPECT相比,由于活性降低了几个数量级,可靠的定量面临挑战,这导致检测到的计数非常低、存在多个光电峰、这些同位素的发射光谱有大量重叠以及SPECT中的图像退化效应。为了解决这些问题,我们提出了一种多能量窗口投影域定量(MEW - PDQ)方法,该方法直接使用来自多个能量窗口的SPECT投影联合估计钍 - 227和镭 - 223的区域活性摄取。我们在使用基于钍 - 227的α - RPTs治疗前列腺癌骨转移患者成像的背景下,使用拟人化数字体模进行了逼真的模拟研究来评估该方法。在虚拟成像试验中,以及在区域内摄取存在中等程度的异质性和各种区域支持定义存在中等程度不准确的情况下,所提出的方法对两种同位素都产生了可靠(准确且精确) 的区域摄取估计,并且在不同病变大小和对比度方面优于现有方法。此外,我们证明了使用多个能量窗口的有效性,并且使用所提出的方法估计摄取的方差接近克拉美 - 罗下界定义的理论极限。