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A prospective IRB approved trial was performed to evaluate diffusion MRI in predicting early response to therapy in patients with primary brain tumors. Thirty-four patients with WHO grade III (n=7) or WHO grade IV (n=27) glioma were examined by diffusion MRI 5.2 +/- 0.6 days (mean +/- SEM) prior to the start of treatment and again 3.1 +/- 0.1 weeks later. To assess the utility of diffusion MRI patients were stratified by standard radiographic response at 9.7 +/- 0.4 weeks from the start of treatment based upon WHO criteria.
For fDM analysis, the pre- and 3 week diffusion weighted images were co-registered using a mutal information algorithmn and differences in tumor water diffusion values were calculated on a voxel-by-voxel basis (see Figure 1). Functional diffusion maps (fDM) were then constructed by segmenting regions within the tumors into 3 categories: areas where diffusion increased in response to treatment (colored red), where diffusion decreased in response to treatment (colored blue), and where there was no significant change in diffusion following treatment. These fDM parameters were then used to evaluate response to treatment.
Not enough patients were available for a training population and test population, so a leave-one-out cross validation strategy was utilized to partially correct for this bias and is represented in all analyses. fDM was then correlated with radiographic response (RR), time to progression (TTP), and overall survival (OS).
Thirty-three of 34 patients were treated with 3D-conformal external beam radiotherapy (using 6 MV or greater photons) using a shrinking-field technique to a median dose of 70 Gy. Thirty-one of 34 patients also received chemotherapy: concurrent with radiation (n=8), adjuvantly (n=26), or in salvage (n=13).
Median follow-up for all patients was 10.0 months and for patients still alive was 13.1 months.
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Example of a Patient with Progressive Disease:
Example of a Patient with Stable Disease:
Example of a Patient with a Partial Response: