Bianchi Anna, Selva Anna, Bortot Davide, Fazzi Alberto, Mazzucconi Davide, Conte Valeria
Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Legnaro, Legnaro, Padua, Italy.
Dipartimento di energia, Politecnico di Milano, Milano, Milano, Italy.
Med Phys. 2025 Aug;52(8):e18005. doi: 10.1002/mp.18005.
It is well established that different types of radiation cause varying degrees of biological damage, even when delivered at the same physical dose. This variability arises from differences in the spatial distribution of energy deposition at the subcellular level. Understanding this is critical for improving radiation therapy techniques, particularly hadron therapy, where precise beam characterization is essential for optimizing treatment plans. Traditional dosimetric approaches focus primarily on quantitative dose measurements, but a deeper understanding of the biological effectiveness of radiation requires additional information.
The MUSICA project, funded by the 5 scientific commission of the Italian National Institute for Nuclear Physics, aims to develop an innovative microdosimeter that will enhance conventional dosimetry by incorporating qualitative insights into radiation interactions at the cellular and subcellular levels. By measuring physical parameters correlated with biological effectiveness, this detector provides a more comprehensive characterization of radiation quality. A specific application in hadron therapy, particularly proton therapy, is expected to improve treatment accuracy and patient outcomes by refining dose distributions and radiobiological effectiveness models.
Radiation-induced damage occurs across multiple scales, from DNA (≈2 nm) to the entire cell nucleus (≈10 µm). The stochastic spatial distribution of energy deposition can be experimentally investigated using microdosimetric techniques. A widely used approach relies on tissue-equivalent gas proportional counters (TEPCs), which enable measurement of microscopic energy deposition in a manner representative of human tissue. While previous studies with TEPCs primarily focused on chromosomal-scale sites (<2 µm), characterizing energy deposition at the scale of entire nuclei (≈10 µm) has often relied on solid-state detectors. However, gas microdosimeters offer advantages in sensitivity, geometric flexibility, and tissue equivalence. This project introduces a novel multi-site TEPC capable of performing microdosimetric measurements at two distinct site sizes (e.g., 1 and 10 µm) within a single measurement session, without requiring gas pressure adjustments. The detector achieves this by incorporating two charge collection regions, enabling simultaneous characterization at both microscopic scales. This unique capability facilitates the direct comparison of radiation interactions at different spatial scales, potentially leading to a more refined understanding of how ionizing radiation damages living matter.
The performance of the multi-site TEPC was evaluated by characterizing its response to different radiation qualities and site sizes. Preliminary results indicate that the detector effectively captures variations in energy deposition patterns, providing valuable data for assessing radiation quality. The two-dimensional microdosimetric information obtained with this detector offers insights into the relationship between physical parameters of the ionizing radiation field and biological effectiveness, which could contribute to the development of improved radiobiological models.
The innovative microdosimetric detector represents a significant advancement in radiation quality assessment. By enabling simultaneous characterization at multiple spatial scales, this technology bridges the gap between conventional dosimetry and radiobiological modeling. The ability to integrate qualitative and quantitative dosimetric data could lead to more accurate treatment planning in proton therapy and other applications in radiation medicine. Future studies will further explore the potential of this detector to refine current radiobiological models and enhance clinical outcomes in hadron therapy.
众所周知，即使物理剂量相同，不同类型的辐射也会造成不同程度的生物损伤。这种变异性源于亚细胞水平能量沉积的空间分布差异。了解这一点对于改进放射治疗技术至关重要，尤其是强子治疗，其中精确的束流表征对于优化治疗计划必不可少。传统的剂量测定方法主要侧重于定量剂量测量，但要更深入地了解辐射的生物有效性还需要更多信息。
由意大利国家核物理研究所的5个科学委员会资助的MUSICA项目旨在开发一种创新的微剂量计，通过纳入细胞和亚细胞水平辐射相互作用的定性见解来增强传统剂量测定。通过测量与生物有效性相关的物理参数，该探测器能更全面地表征辐射质量。预计在强子治疗，特别是质子治疗中的具体应用将通过优化剂量分布和放射生物学有效性模型来提高治疗准确性和患者预后。
辐射引起的损伤发生在多个尺度上，从DNA（约2纳米）到整个细胞核（约10微米）。能量沉积的随机空间分布可以使用微剂量测定技术进行实验研究。一种广泛使用的方法依赖于组织等效气体正比计数器（TEPC），它能够以代表人体组织的方式测量微观能量沉积。虽然以前使用TEPC的研究主要集中在染色体尺度的位点（<2微米），但表征整个细胞核尺度（约10微米）的能量沉积通常依赖于固态探测器。然而，气体微剂量计在灵敏度、几何灵活性和组织等效性方面具有优势。该项目引入了一种新型多位点TEPC，能够在单次测量中在两个不同的位点尺寸（例如1和10微米）下进行微剂量测量，而无需调整气压。该探测器通过结合两个电荷收集区域来实现这一点，从而能够在两个微观尺度上同时进行表征。这种独特的能力有助于直接比较不同空间尺度上的辐射相互作用，有可能更精确地理解电离辐射如何损伤生物物质。
通过表征多位点TEPC对不同辐射质量和位点尺寸的响应来评估其性能。初步结果表明，该探测器有效地捕捉了能量沉积模式的变化，为评估辐射质量提供了有价值的数据。用该探测器获得的二维微剂量信息深入了解了电离辐射场的物理参数与生物有效性之间的关系，这可能有助于改进放射生物学模型的开发。
创新的微剂量探测器代表了辐射质量评估的重大进展。通过能够在多个空间尺度上同时进行表征，这项技术弥合了传统剂量测定与放射生物学建模之间的差距。整合定性和定量剂量数据的能力可能会在质子治疗和放射医学的其他应用中实现更准确的治疗计划。未来的研究将进一步探索该探测器在改进当前放射生物学模型和提高强子治疗临床疗效方面的潜力。
