Gagan Acharya

Gagan Acharya, Erfan Nozari

Recent advances in neurotechnologies and decades of scientific and clinical research have made closed-loop electrical neuromodulation one of the most promising avenues for the treatment of drug-resistant epilepsy (DRE), a condition that affects over 15 million individuals globally. Yet, with the existing clinical state of the art, only 18% of patients with DRE who undergo closed-loop neuromodulation become seizure-free. In a recent study, we demonstrated that a simple proportional feedback policy based on the framework of passivity-based control (PBC) can significantly outperform the clinical state of the art. However, this study was purely numerical and lacked rigorous mathematical analysis. The present study addresses this gap and provides the first rigorous analysis of PBC for the closed-loop control of epileptic seizures. Using the celebrated Epileptor neural mass model of epilepsy, we analytically demonstrate that (i) seizure dynamics are, in their standard form, neither passive nor passivatable, (ii) epileptic dynamics, despite their lack of passivity, can be stabilized by sufficiently strong passive feedback, and (iii) seizure dynamics can be passivated via proper output redesign. To our knowledge, our results provide the first rigorous passivity-based analysis of epileptic seizure dynamics, as well as a theoretically-grounded framework for sensor placement and feedback design for a new form of closed-loop neuromodulation with the potential to transform seizure management in DRE.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.