Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience

Purpose 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 is to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35T MRI-guided radiotherapy system. Methods A diffusion prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) sequence on a 0.35T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantify 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 0.40×10-3 and 2.10×10-3 mm2/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 quantify 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. Results The proposed DP-TSE passed the spatial integrity test (<1mm within 100mm radius and <2mm within 175mm radius) under the three orthogonal orientations. The detected errors were 0.474±0.355mm, 0.475±0.287mm, and 0.546±0.336mm 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 quantification errors, whereas it is optional for DP-TSE. At 0°C, the two sequences provided accurate quantification 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 1.6mm overall, whereas it could be greater than 12mm 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. Conclusion 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. This article is protected by copyright. All rights reserved.