Fujimoto Koya, Shiinoki Takehiro, Yuasa Yuki, Tanaka Hidekazu
Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8535, Japan.
Med Phys. 2021 Mar;48(3):1286-1298. doi: 10.1002/mp.14723. Epub 2021 Feb 6.
Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis.
Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4).
The mean ± standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54 ± 0.33 mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r = 0.87, P < 0.001). Furthermore, the estimated whole liver elasticity was statistically significantly correlated with the UTE (r = 0.84, P < 0.001), APRI score (r = 0.62, P = 0.005), and FIB-4 score (r = 0.54, P = 0.021).
In this study, liver elasticity was estimated through FEM-based simulation and actual respiratory-induced liver displacement obtained from 4DCT images. Furthermore, we assessed that the estimated elasticity of the liver's right lobe was strongly correlated with the UTE. Therefore, the estimated elasticity has the potential to be a feasible imaging biomarker for assessing liver fibrosis using only 4DCT images without additional inspection or equipment costs. Because our results were derived from a limited sample of 20 patients, it is necessary to evaluate the accuracy of elasticity estimation for each liver segment on larger groups of biopsied patients to utilize liver elasticity information for radiotherapy planning.
当前的放射治疗计划程序通常仅基于解剖学信息设计,并使用不包含器官功能信息的计算机断层扫描(CT)图像。在本研究中,我们开发了一种使用有限元方法(FEM)和放射治疗计划期间获取的四维CT(4DCT)图像来估计肝脏弹性的方法,随后我们评估了其作为肝纤维化生物标志物的可行性。
招募了20名接受4DCT和基于超声的瞬时弹性成像(UTE)的患者。所有患者均患有慢性肝病或肝硬化。对20名患者的肝脏右叶进行了UTE肝脏弹性测量。在20名患者中的18名患者中可获得天冬氨酸转氨酶(AST)与血小板比值指数(APRI)和纤维化-4指数(FIB-4)的血清生物标志物,这些标志物在接受4DCT后1周内进行测量。使用实际(通过可变形图像配准)和模拟(通过有限元方法)呼吸诱导位移来确定呼气和吸气终点处获得的4DCT图像之间的位移。通过最小化实际和模拟呼吸诱导位移之间的误差来优化肝脏模型每个元素的弹性。然后,使用估计的弹性图将每位患者的估计肝脏弹性定义为肝脏右叶和整个肝脏的平均杨氏模量。评估估计的肝脏弹性与通过UTE获得的弹性以及两种血清生物标志物(APRI和FIB-4)之间的相关性。
肝脏模型中实际和模拟呼吸诱导位移之间误差的平均值±标准差(SD)为0.54±0.33mm。估计的肝脏右叶弹性与UTE在统计学上显著相关(r = 0.87,P < 0.001)。此外,估计的整个肝脏弹性与UTE(r = 0.84,P < 0.001)、APRI评分(r = 0.62,P = 0.005)和FIB-4评分(r = 0.54,P = 0.021)在统计学上显著相关。
在本研究中,通过基于有限元方法的模拟和从4DCT图像获得的实际呼吸诱导肝脏位移来估计肝脏弹性。此外,我们评估了估计的肝脏右叶弹性与UTE密切相关。因此,估计的弹性有可能成为一种可行的成像生物标志物,用于仅使用4DCT图像评估肝纤维化,而无需额外的检查或设备成本。由于我们的结果来自20名患者的有限样本,有必要在更大的活检患者群体中评估每个肝段弹性估计的准确性,以便将肝脏弹性信息用于放射治疗计划。