Diffusion and Perfusion MRI Predicts Response Preceding and Shortly After Radiosurgery to Brain Metastases: A Pilot Study

Abstract

Background and purpose: To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS).

Methods: In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria.

Results: We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12 of 16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = .041). Pre-SRS extracellular extravascular volume fraction, v_e , and volume transfer coefficient, K^trans , derived from DCE-MRI were higher in nonresponders versus responders (q = .041).

Conclusions: Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

Keywords: Brain metastases; DCE-MRI; DWI; stereotactic radiosurgery; treatment response.

Figure 1.

Representative pre- and early post-SRS MR images from an 80-year-old female with right occipital lobe brain metastasis that eventually demonstrated PD on follow-up. Top panel: The yellow rectangle surrounds the metastatic lesion on the pre-SRS DWI (b=0 s/mm²) image. Diffusion coefficient (D) (× 10⁻³ mm²/s), pseudo-diffusion coefficient (D*) (× 10⁻³ mm²/s), and perfusion fraction (f) maps are zoomed in at the locations of the regions of interest (ROIs). The lesion volume was unchanged within 72 hours of SRS. Bottom panel: The yellow rectangle surrounds the metastatic lesion on the pre-SRS T1-postcontrast image. K^trans (min⁻¹), volume fraction of extracellular extravascular space (v_e), and vascular volume (v_p) maps are zoomed in at the locations of the ROIs.

Figure 2.

Representative pre-SRS and early post-SRS MR images from a 51-year-old female with right frontal lobe metastasis that eventually demonstrated CR on follow-up. Top panel: The yellow rectangle surrounds the metastatic lesion on pre-SRS diffusion weighted (b=0 s/mm²) image. Diffusion coefficient (D) (×10⁻³ mm²/s), pseudo-diffusion coefficient (D*) (×10⁻³ mm²/s), and perfusion fraction (f) maps are zoomed at the locations of regions of interests (ROIs). The lesion volume was reduced on early post-SRS imaging. Bottom panel: The yellow rectangle surrounds the metastatic lesion on pre-SRS T1-postcontrast image. K^trans (min⁻¹), volume fraction of extracellular extravascular space (v_e), and vascular volume (v_p) maps are zoomed at the locations of ROIs.

Figure 3.

ROC curves for post-SRS f mean and median and D* and pre-SRS v_e median and k_trans mean and median. The area under the curve (AUC) for post-SRS perfusion fraction (f) mean, f median, and pseudo-diffusion coefficient (D*) mean, and pre-SRS Ktrans mean, Ktrans median, and volume fraction of extracellular extravascular space (ve) median was 0.88, 0.93, 0.84, 0.79, 0.85, and 0.78 respectively.

Figure 4.

Univariate analysis of DWI and DCE-MRI metrics using WRST and comparison of DWI and DCE-MRI metrics pre- and post-SRS using WSRT. Lesions that progressed had a higher perfusion fraction (f) mean and median than those that did not (0.416 vs. 0.336, q = 0.041; 0.500 vs. 0.358, q = 0.033 respectively). Lesions that responded to SRS had a lower pre-SRS k_trans mean, k_trans median, and v_e median than those that did not (0.044 vs. 0.093, q = 0.041; 0.032 vs 0.080, q = 0.033; 0.089 vs. 0.181, q = 0.041 respectively). ADC mean and median trended higher in lesions post-SRS than pre-SRS (p = 0.0522 and 0.065 respectively). V_p was lower in lesions post-SRS than pre-SRS (p=0.009). ADC, apparent diffusion coefficient. K^trans, index of tumor vascular permeability. V_e, volume fraction of extracellular extravascular space. V_p, vascular volume.