Cerebral Microbleeds (CMBs) are chronic deposits of small blood products in the brain tissues, which have explicit relation to various cerebrovascular diseases depending on their anatomical location, including cognitive decline, intracerebral hemorrhage, and cerebral infarction. However, manual detection of CMBs is a time-consuming and error-prone process because of their sparse and tiny structural properties. The detection of CMBs is commonly affected by the presence of many CMB mimics that cause a high false-positive rate (FPR), such as calcification and pial vessels. This paper proposes a novel 3D deep learning framework that does not only detect CMBs but also inform their anatomical location in the brain (i.e., lobar, deep, and infratentorial regions). For the CMB detection task, we propose a single end-to-end model by leveraging the U-Net as a backbone with Region Proposal Network (RPN). To significantly reduce the FPs within the same single model, we develop a new scheme, containing Feature Fusion Module (FFM) that detects small candidates utilizing contextual information and Hard Sample Prototype Learning (HSPL) that mines CMB mimics and generates additional loss term called concentration loss using Convolutional Prototype Learning (CPL). The anatomical localization task does not only tell to which region the CMBs belong but also eliminate some FPs from the detection task by utilizing anatomical information. The results show that the proposed RPN that utilizes the FFM and HSPL outperforms the vanilla RPN and achieves a sensitivity of 94.66% vs. 93.33% and an average number of false positives per subject (FPavg) of 0.86 vs. 14.73. Also, the anatomical localization task further improves the detection performance by reducing the FPavg to 0.56 while maintaining the sensitivity of 94.66%.
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