A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men with a subset inevitably presenting with metastatic disease to the bone. A well-recognized limitation in evaluating new treatments for metastatic PCa is the inability to use imaging to objectively assess response therapy. In this study, we evaluated the feasibility of clinically translating the functional diffusion map (fDM) imaging biomarker for quantifying the spatiotemporal effects of bone tumor response in a patient treated for metastatic PCa with bone metastases. A patient beginning therapy was scanned using MRI before treatment and again at 2 and 8 weeks post-treatment initiation to quantify changes in tumor diffusion values. Three metastatic lesions were identified for fDM analysis, all of which all demonstrated an early increase in diffusion values at 2 weeks, which increased further at 8 weeks post-treatment initiation. This finding correlated with a decrease in the patient's prostate-specific antigen (PSA) levels suggestive of patient response. CT, bone scans, and anatomic MRI images obtained posttreatment were found to be uninformative for the assessment of treatment effectiveness. This study presents the feasibility of fDM-measurements in osseous lesions over time and shows that changes in fDM values were consistent with therapeutic response. Thus, the fDM imaging biomarker may provide a quantifiable therapeutic endpoint to assess response in patients with metastatic bone cancer.

Keywords: Metastatic prostate cancer; androgen deprivation therapy; diffusion MRI; functional diffusion map; imaging biomarker.

Figure 1

Bone scintigraphy. Posterior bone scintigraphic image of the pelvis shows increased uptake of the sacrum and left femoral head lesions, with two additional foci of uptake in each ilium. Follow-up bone scintigraphy 9 weeks after therapy shows increased intensity of the uptake.

Figure 2

Computed tomography. Axial CT images (A) before and (B) 7 weeks after treatment show a mixed lucent and sclerotic metastasis (yellow arrow) of the left femoral head. Axial CT images reveal the sacral lesion (red arrow) and ilium lesion (green arrow) (C) before and (D) 7 weeks after treatment.

Figure 3

T1-weighted MRI. Axial T1-weighted MR images of the femoral head (A) before and (B) 7 weeks after treatment show heterogeneous marrow replacement (yellow arrow). Axial T1-weighted MR images of the sacrum (red arrow) and ilium (green arrow) (C) before and (D) 7 weeks after treatment.

Figure 4

Functional diffusion maps. Regional changes of ADC are plotted on the image to provide a visual representation of areas with increased ADC (red voxels), decreased ADC (blue voxels), and areas where ADC did not change significantly (green voxels). fDM analysis of the femoral head lesion (yellow arrows) at (A) 2 and (B) 8 weeks after treatment initiation revealed distinct regions of red voxels signifying areas with significant increases in ADC (>26 x 10^-6 mm²/s). fDM analysis of the sacral lesion (red arrows) at (C) 2 and (D) 8 weeks after treatment revealed significant regions of increased ADC as depicted by the red voxels. fDM analysis of the ilium lesion (green arrows) at (E) 2 and (F) 8 weeks after treatment show large regions of increased ADC values (red voxels).

Figure 5

Comparison of mean ADC versus fDM with respect to pre-therapy baseline. At 2 weeks post-therapy, a decrease of 0.7 ± 4.8% was observed by comparing mean ADC whereas fDM demonstrated a 24 ± 1.6% increase in ADC. At 8 weeks, mean ADC increased by 8.3 ± 4.3% whereas fDM demonstrated a 38 ± 5.2% increase in ADC.