Localizing Image-Based Biomarker Regression Without Training Masks: A New Approach to Biomarker Discovery

Biomarker inference from biomedical images is one of the main tasks of medical image analysis. Standard techniques follow a segmentation-and-measure strategy, where the structure is first segmented and then the measurement is performed. Recent work has shown that such strategy could be replaced by a direct regression of the biomarker value in using regression networks. While achieving high correlation coefficients, such techniques operate as a 'black-box', not offering quality-control images. We present a methodology to regress the biomarker from the image while simultaneously computing the quality control image. Our proposed methodology does not require segmentation masks for training, but infers the segmentations directly from the pixels that used to compute the biomarker value. The network proposed consists of two steps: a segmentation method to an unknown reference and a summation method for the biomarker estimation. The network is optimized using a dual loss function, L2 for the biomarkers and an L1 to enforce sparsity. We showcase our methodology in the problem of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) inference in a single slice from chest-CT images. We use a database of 7000 cases to which only the value of the biomarker is known for training and a test set of 3000 cases with both, biomarkers and segmentations. We achieve a correlation coefficient of 0.97 for PMA and 0.98 for SFA with respect to the reference standard. The average DICE coefficient is of 0.88 (PMA) and 0.89 (SFA). Comparing with standard segment-and-measure techniques, we achieve the same correlation for the biomarkers but smaller DICE coefficients in segmentation. Such is of little surprise, since segmentation networks are the upper limit of performance achievable, and we are not using segmentation masks for training. We can conclude that it is possible to infer segmentation masks from biomarker regression networks.