Bache Steven T, Juang Titania, Belley Matthew D, Koontz Bridget F, Adamovics John, Yoshizumi Terry T, Kirsch David G, Oldham Mark
Duke University Medical Physics Graduate Program, Durham, North Carolina 27705.
Duke University Medical Center, Durham, North Carolina 27710.
Med Phys. 2015 Feb;42(2):846-55. doi: 10.1118/1.4905489.
Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1-15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm(3)) optical computed tomography (optical-CT) dose read-out.
Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half.
Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%.
This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.
最近已开发出结合锥束CT图像引导的精密小动物辐照仪,可用于探索临床前环境中先进放射治疗的疗效。微型立体定向体部放射治疗(microSBRT)是一种备受关注的技术,其射野尺寸在1-15毫米范围内。由于缺乏能够在具有足够高空间分辨率的代表性模体中全面测量三维(3D)剂量分布的可用方法,因此验证microSBRT治疗剂量传递的准确性具有挑战性。这项工作介绍了一种潜在的解决方案,即与超高分辨率(0.3毫米³)光学计算机断层扫描(光学CT)剂量读出兼容的解剖学精确的啮齿动物形态3D剂量仪。
通过直接从大鼠和小鼠的X射线CT数据集中定义的轮廓3D打印啮齿动物解剖结构的模具,并使用这些模具从Presage创建组织等效的放射变色3D剂量仪,来制作啮齿动物形态剂量仪。通过首先3D打印脊柱模具,然后形成高Z值骨等效脊柱插入物,将解剖学精确的脊柱纳入一些剂量仪中。然后将该脊柱插入物放置在组织等效体模内。高Z值脊柱插入物实现了代表性的锥束CT图像引导放射治疗(IGRT)靶向。在辐照时,剂量仪中会发生与吸收剂量成比例的光学密度线性放射变色变化,并使用高分辨率(0.5毫米各向同性体素)的光学CT读出。光学CT数据通过两种方式转换为绝对剂量:(i)使用来自同一批次的其他Presage剂量仪得出的校准曲线,以及(ii)使用由基于氧化钇的纳米晶闪烁体组成的新型探测器在一点独立测量校准剂量,该探测器的有效长度为亚毫米级。进行了一次microSBRT脊柱治疗,包括在225 kVp下进行180°连续弧,射野尺寸为20×10毫米。使用上述Presage/光学CT 3D剂量测定系统评估剂量响应,并使用放置在已切成两半的啮齿动物形态剂量仪内EBT2放射变色胶片在选定平面进行独立验证。
通过利用大鼠CT轮廓的3D打印模具,成功地从Presage放射变色材料制作出了啮齿动物形态3D剂量仪。发现这些剂量仪与高分辨率3D(0.5毫米各向同性体素)的光学CT剂量读出兼容,伪影或噪声最小。由于高Z值脊柱插入物与组织等效Presage材料之间有足够的对比度(CBCT图像上的对比度噪声比约为10),因此使用这些剂量仪可以进行锥束CT图像引导。发现用光学CT测量的等中心剂量与纳米闪烁体测量结果在2.8%以内一致。通过Presage和胶片剂量切片的线轮廓中的最大剂量在3%以内一致,通过每个轮廓的半高宽测量结果在2%以内一致。
这项工作证明了使用3D打印技术制作包含脊柱模拟插入物的解剖学精确的Presage啮齿动物形态剂量仪的可行性。尽管表面不规则且有植入的插入物,但在这些剂量仪上进行高质量的光学CT 3D剂量测定是可行的。在解剖学精确的模体中测量剂量分布的能力代表了一种强大且有用的临床前microSBRT额外验证工具。