Department of Radiological Sciences, University of California, Los Angeles, CA, USA.
Physics and Biology in Medicine IDP, University of California, Los Angeles, CA, USA.
Med Phys. 2017 Oct;44(10):5357-5366. doi: 10.1002/mp.12465. Epub 2017 Aug 12.
Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided radiotherapy system.
A diffusion-prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10 and 2.10 × 10 mm /s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co-registered to the diffusion images as references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared.
The proposed DP-TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW-ssEPI to avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP-TSE and the reference were within 4%, but could be as high as 8% for DW-ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP-TSE, indicating desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP-TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW-ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements.
A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low-field MRI-guided radiotherapy system.
在治疗过程中监测肿瘤反应，并根据肿瘤生物学反馈自适应地修改治疗计划，这可能代表放射治疗的一个新范例。扩散 MRI 在评估和预测放射治疗的肿瘤反应方面显示出巨大的前景。然而，传统的扩散加权单次激发回波平面成像（DW-ssEPI）技术在低场强下存在分辨率有限、严重失真和可能不准确的 ADC 的问题。本研究的目的是开发一种可靠、准确且无失真的扩散 MRI 技术，该技术可用于 0.35 T MRI 引导放射治疗系统上的肿瘤纵向反应评估和自适应放射治疗。
开发了一种扩散准备的涡轮自旋回波读出（DP-TSE）序列，并在 0.35 T MRI 引导放射治疗系统（ViewRay）上与传统的扩散加权单次激发回波平面成像序列进行了比较。使用空间完整性体模来量化和比较两种扩散序列在三个正交方向上的几何精度。在 0 °C 和室温下在扩散体模中评估 ADC 精度，以覆盖 0.40×10 和 2.10×10 mm/s 之间的扩散率范围。在五个不同的日子进行了 10 次室温测量，以评估 DP-TSE 的 ADC 可重复性。纳入了两名胶质母细胞瘤（GBM）患者和六名肉瘤患者，以检查体内可行性。目标注册误差（TRE）用于定量测量，将结构 CT 或 MR 图像与参考的扩散图像进行配准。计算 DP-TSE 和 DW-ssEPI 的 ADC 图，并进行比较。在未在 ViewRay 上接受治疗的患者旁边放置了一个管体模，并比较了该参考管的 ADC 值。
所提出的 DP-TSE 在三个正交方向上通过了空间完整性测试（在 100 毫米半径内的误差<1 毫米，在 175 毫米半径内的误差<2 毫米）。在轴向、冠状和矢状平面中，检测到的误差分别为 0.474±0.355 毫米、0.475±0.287 毫米和 0.546±0.336 毫米。然而，DW-ssEPI 由于严重失真和低信号强度而未能通过测试。必须对 DW-ssEPI 进行噪声校正以避免 ADC 定量误差，而 DP-TSE 则可以选择进行噪声校正。在 0 °C 时，两种序列都提供了准确的定量结果，与参考值的差异<3%。在室温研究中，DP-TSE 和参考值之间的 ADC 差异在 4%以内，但在进行噪声校正后，DW-ssEPI 的差异可能高达 8%。DP-TSE 在 10 次测量中的 ADC 可重复性非常好，变异系数<5%，表明其在基于 ADC 的肿瘤反应评估方面具有良好的稳健性。在 DP-TSE 中，体内 TRE 总体上小于 1.6 毫米，而在 DW-ssEPI 中，TRE 可能大于 12 毫米。对于 GBM 患者，DP-TSE 的 CSF 和脑组织 ADC 值在文献中找到的范围内。六名肉瘤患者中，两种技术之间的 ADC 差异在 8%以内。对于具有相对较低扩散率的参考管，两种扩散序列提供了匹配的测量值。
使用低场强 MRI 引导放射治疗系统，我们展示了一种具有出色几何保真度、准确且可重复的 ADC 测量的扩散技术，可用于肿瘤纵向反应评估。
