Purpose

The most challenging issue in radiation therapy is the non-invasive, accurate assessment of tumor response during treatment. Apparent diffusion coefficient (ADC)1, derived from DW-MRI has shown promise in tumor characterization and assessment of treatment response2. However, geometric distortions associated with the DW-MRI data collected in clinical setting needs to be corrected prior to the calculation of ADC. One of the options for this correction is to use reversed gradient method3,4. This pilot study investigates the use of the reversed gradient correction method in DW-MRI for reduction in geometric distortion and accurate measurement of ADC in treatment response assessment.

Methods

MRI data acquisition: We developed a new phantom for distortion assessment (DA) in DW-MRI (Figure 1). It consists of a 17 x 17 x 17 cm³ polyethylene HD 500 cube, which contains 10 rows and 5 columns of cylindrical tubes (diameter: 14 mm) filled with water and capped at the ends. After phantom studies were performed at room temperature, three head and neck squamous cell carcinoma patients (stage IV) were enrolled for in vivo feasibility study and was approved by local institutional review board. The patients had 4 MRIs (1pre-, 2 intra- treatment [2nd and 3rd week] and 1 post- chemoradiation therapy). All MRI examinations were performed on a 1.5-T scanner (Achieva; Philips Healthcare) with a Philips Sense Flex Medium coil. Standard MR images for localization and T2w Turbo Spin Echo images were obtained followed by DW-MRI acquisition using a single-shot echo planar imaging (TE/TR (ms) = 77/5270; NEX=4, FOV (cm): 23, slice thickness (mm)= 6) with 3 b values of b=0, 600 and 1000 s/mm², respectively. For the reversed gradient correction method3,4, a 2nd DW-MRI acquisition was performed under exactly the same conditions, supposing that the spatial shifting of the signal occurred in the opposite direction along the y axis. MRI data analysis: Regions of interest (ROIs) were delineated in the cylindrical tubes filled with water in the phantom-DA, using ImageJ (http://imagej.nih.gov/ij/.). For the patient MRI studies, the radiation oncologist contoured the ROIs on the tumor using treatment planning vendor system (FocalSim). We used the 2 sets of DW-MRI images collected for each b values (b= 0, 600 and 1000 s/mm²) and analyzed the data with the open source SPM8 software (http://www.fil.ion.ucl.ac.uk/spm/software/spm8/) selecting the HySCO options to apply the reversed gradient method3,4. We used the standard settings for the method: dimension of phase encoding y (Antero-Posterior Direction), maximal data resolution full; smoothing of spline-interpolation 0.1, weight for "diffusion" regularizer 50; weight for "Jacobian" regularizer105. The corrected set of DW-MRI images were used to calculate ADC (mono-exponential fitting of the data) on a voxel-wise basis. ADC was also calculated from the 2 raw DW-MRI datasets. Geometric distortion correction was assessed using mutual information metrics6,7 via registration of the raw and corrected DW-MRI images with T2-weighted MR images using a in-home software ( ARTFIBio 0.6.2) 8.

Results

Phantom study: No significant difference was observed in ADC values of water derived from the raw ((2.13 ± 0.19) × 10-3 mm²/s) and corrected ((2.19 ± 0.05) × 10-3 mm² /s) DW-MRI data at room temperature. The mutual information metric values reflect their dependence on the b-value (13% for b=0, 23% for b=600 and 36% for b=1000s/mm2) [Table 1]. Patients study: The mutual information metric values for the pre- MRIs in three different patients for different b-values obtaining an average registration improvement of 21% [Table 2]. In one of the three patients tumor response was evaluated by measuring the difference in ADC values during treatment for raw and corrected datasets. The voxel-wise analysis of the tumor showing variation of ADC with treatment is closely clustered for corrected datasets rather than raw datasets and exhibits significant difference (p<0.01) in calculated ADC between corrected and raw images. (Figure 3).

Discussion

ADC has shown promise for mathematically modeling of the individual tumor response9. The DW-MRI data corrected by the reversed gradient method points out the feasibility of accurately measuring ADC through a voxel-wise approach for tumor response assessment. DW-MRI phantoms have been developed for verifying ADC value mostly of water10, 11, and do not focus on evaluating geometric distortion. Thus, our new phantom-DA provides the DW-MRI imaging community with a new tool to evaluate geometric distortions with mutual information metric.

Conclusion

The reverse gradient method may find wider applicability after validation in a larger cancer patient population for tumor response assessment which needs accurate measurement of ADC.

Acknowledgements

The National Health Institute of Spain is supporting this work by the ISCIII Grant PI11/02035 and DTS14/00188, and BIOCAPS project (FP7/REGPOT-2012-2013.1 under grant agreement n° 316265) that also partially supported this research.

References

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