Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using 18FDG and 64Cu-DOTA-Trastuzumab Positron Emission Tomography Studies.

Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency. The fits were also compared against previously published results from institutions using the full resolution series. The model was then evaluated on a separate cohort for validity of biomarker indications. Finally, the model was used as a fundamental part of predicting response to neoadjuvant chemotherapy (NACT).

Results: Temporally subsampled DCE-MRI series yield perfusion fit variations on the scale of 1% of the tumor median value when input frames are varied. Fits generated from pseudoclinical series are within the variation range seen between imaging sites (ρ = 0.55), voxel-wise. The model also demonstrates significant correlations with orthogonal positron emission tomography imaging, indicating potential for use as a biomarker proxy. Specifically, using the perfusion fits as the grounding for a biophysical simulation of response, we correctly predict the pathologic complete response status after NACT in 15 of 18 patients, for an accuracy of 0.83, with a specificity and sensitivity of 0.83 as well.

Conclusion: Clinical DCE-MRI data may be leveraged to provide stable perfusion fit results and indirectly interrogate the tumor microenvironment. These fits can then be used downstream for prediction of response to NACT with high accuracy.