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Abstract：
Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.
摘要：
使用90Y选择性内部放射疗法（SIRT）治疗肝脏恶性肿瘤可能会损害功能性肝实质。评估功能性实质变化并开发吸收剂量（AD）毒性模型可以帮助接受SIRT的患者的临床管理。我们旨在确定在SIRT之前和之后，90YPETAD体素图与动态gadoxetic酸增强MRI得出的非肿瘤肝脏（NTL）功能的空间变化之间是否存在相关性。方法：对11例接受90YSIRT治疗的患者，在治疗前后进行动态gadoxetic酸增强MRI扫描。从MRI数据生成直接量化空间肝实质功能的Gadoxetic酸摄取率（k1）图。基于体素的AD地图，来自90YPET/CT扫描，根据AD分类。SIRT前和后k1图被共同注册到AD图。计算每个箱中k1损失的绝对和百分比，作为肝功能损失的量度，对每位患者的k1丢失和AD之间的Spearman相关系数进行评估。患者的平均k1损失符合基于AD的3参数逻辑函数。根据病变类型将患者进一步分为亚组，基线白蛋白-胆红素评分和丙氨酸转氨酶水平，剂量-体积效应，和SIRT治疗的数量。结果：在大多数患者（8/11）中，k1绝对丢失和百分比丢失与AD之间存在显着正相关（ρ=0.53-0.99，P<0.001）。9例患者的平均k1损失也显示出与AD的显着强相关性（ρ≥0.92，P<0.001）。AD患者k1丢失的平均百分比为28%，逻辑函数模型表明，在约100Gy时，k1损失约25%。患者亚组之间的分析表明，在肝细胞癌患者中k1丢失更大，更高的丙氨酸转氨酶水平，接受70Gy或更高AD的NTL的分数更大，和连续SIRT治疗。结论：多模态成像的新应用证明了90YSIRTAD与空间功能性肝实质降解之间的相关性，表明较高的AD与局部肝细胞功能的较大丧失有关。有了开发的响应模型，PET衍生的AD图可以潜在地用于识别肝脏中的局部损伤并增强治疗策略。
