Medical Physics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Department of Electronics Information and Bioengineering (DEIB), Politecnico di Milano, Milan, Italy.
PLoS One. 2021 Feb 26;16(2):e0247748. doi: 10.1371/journal.pone.0247748. eCollection 2021.
To study a robust and reproducible procedure to investigate a relation between focal brain radiotherapy (RT) low doses, neurocognitive impairment and late White Matter and Gray Matter alterations, as shown by Diffusion Tensor Imaging (DTI), in children.
Forty-five patients (23 males and 22 females, median age at RT 6.2 years, median age at evaluations 11.1 years) who had received focal RT for brain tumors were recruited for DTI exams and neurocognitive tests. Patients' brains were parceled in 116 regions of interest (ROIs) using an available segmented atlas. After the development of an ad hoc, home-made, multimodal and highly deformable registration framework, we collected mean RT doses and DTI metrics values for each ROI. The pattern of association between cognitive scores or domains and dose or DTI values was assessed in each ROI through both considering and excluding ROIs with mean doses higher than 75% of the prescription. Subsequently, a preliminary threshold value of dose discriminating patients with and without neurocognitive impairment was selected for the most relevant associations.
The workflow allowed us to identify 10 ROIs where RT dose and DTI metrics were significantly associated with cognitive tests results (p<0.05). In 5/10 ROIs, RT dose and cognitive tests were associated with p<0.01 and preliminary RT threshold dose values, implying a possible cognitive or neuropsychological damage, were calculated. The analysis of domains showed that the most involved one was the "school-related activities".
This analysis, despite being conducted on a retrospective cohort of children, shows that the identification of critical brain structures and respective radiation dose thresholds is achievable by combining, with appropriate methodological tools, the large amount of data arising from different sources. This supported the design of a prospective study to gain stronger evidence.
研究一种稳健且可重复的方法，以调查儿童局灶性脑放射治疗（RT）低剂量与神经认知障碍以及晚期白质和灰质改变之间的关系，这些改变通过弥散张量成像（DTI）显示。
共招募了 45 名（男 23 名，女 22 名，中位 RT 年龄为 6.2 岁，中位评估年龄为 11.1 岁）接受局灶性 RT 治疗脑肿瘤的患者进行 DTI 检查和神经认知测试。使用现有的分割图谱，将患者的大脑分为 116 个感兴趣区（ROI）。在开发了一个专门的、自制的、多模态和高度可变形的配准框架之后，我们收集了每个 ROI 的平均 RT 剂量和 DTI 指标值。通过考虑和排除平均剂量高于处方剂量 75%的 ROI，评估了认知评分或领域与剂量或 DTI 值之间的关联模式。随后，为了选择与神经认知障碍相关的最相关的关联，选择了一个初步的剂量阈值来区分有和没有神经认知障碍的患者。
该工作流程使我们能够在 10 个 ROI 中识别出 RT 剂量和 DTI 指标与认知测试结果显著相关（p<0.05）。在 5/10 个 ROI 中，RT 剂量和认知测试结果呈显著相关（p<0.01），并计算出了初步的 RT 阈值剂量值，表明可能存在认知或神经心理损害。对域的分析表明，最相关的域是“学校相关活动”。
尽管这是一项对儿童回顾性队列的研究，但该分析表明，通过适当的方法工具，结合来自不同来源的大量数据，可以确定关键的脑结构及其相应的辐射剂量阈值。这支持了设计一项前瞻性研究以获得更强有力的证据。
