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Microstructural changes associated with degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) have been studied using Diffusion Tensor Imaging (DTI). However, these studies show inconsistent results, mainly due to methodological variations in delineation of SNc. To mitigate this, our work aims to construct a probabilistic atlas of SNc based on a 3D Neuromelanin Sensitive MRI (NMS‐MRI) sequence and demonstrate its applicability to investigate microstructural changes on a large dataset of PD. Using manual segmentation and deformable registration we created a novel SNc atlas in the MNI space using NMS‐MRI sequences of 27 healthy controls (HC). We first quantitatively evaluated this atlas and then employed it to investigate the micro‐structural abnormalities in SNc using diffusion MRI from 133 patients with PD and 99 HCs. Our results demonstrated significant increase in diffusivity with no changes in anisotropy. In addition, we also observed an asymmetry of the diffusion metrics with a higher diffusivity and lower anisotropy in the left SNc than the right. Finally, a multivariate classifier based on SNc diffusion features could delineate patients with PD with an average accuracy of 71.7%. Overall, from this work we establish a normative baseline for the SNc region of interest using NMS‐MRI while the application on PD data emphasizes on the contribution of diffusivity measures rather than anisotropy of white matter in PD.

We propose a CNN based technique that aggregates feature maps from its multiple layers that can localize abnormalities with greater details as well as predict pathology under consideration. Existing class activation mapping (CAM) techniques extract feature maps from either the final layer or a single intermediate layer to create the discriminative maps and then interpolate to upsample to the original image resolution. In this case, the subject specific localization is coarse and is unable to capture subtle abnormalities. To mitigate this, our method builds a novel CNN based discriminative localization model that we call high resolution CAM (HR-CAM), which accounts for layers from each resolution, therefore facilitating a comprehensive map that can delineate the pathology for each subject by combining low-level, intermediate as well as highlevel features from the CNN. Moreover, our model directly provides the discriminative map in the resolution of the original image facilitating finer delineation of abnormalities. We demonstrate the working of our model on a simulated abnormalities data where we illustrate how the model captures finer details in the final discriminative maps as compared to current techniques. We then apply this technique: (1) to classify ependymomas from grade IV glioblastoma on T1weighted contrast enhanced (T1-CE) MRI and (2) to predict Parkinson's disease from neuromelanin sensitive MRI. In all these cases we demonstrate that our model not only predicts pathologies with high accuracies, but also creates clinically interpretable subject specific high resolution discriminative localizations. Overall, the technique can be generalized to any CNN and carries high relevance in a clinical setting.

Glioblastoma is a highly infiltrative neoplasm with a high propensity of recurrence. The location of recurrence usually cannot be anticipated and depends on various factors, including the surgical resection margins. Currently, radiation planning utilizes the hyperintense signal from T2‐FLAIR MRI and is delivered to a limited area defined by standardized guidelines. To this end, noninvasive early prediction and delineation of recurrence can aid in tailored targeted therapy, which may potentially delay the relapse, consequently improving overall survival. In this work, we hypothesize that radiomics‐based phenotypic quantifiers may support the detection of recurrence before it is visualized on multimodal MRI. We employ retrospective longitudinal data from 29 subjects with a varying number of time points (three to 13) that includes glioblastoma recurrence. Voxelwise textural and intensity features are computed from multimodal MRI (T1‐contrast enhanced [T1CE], FLAIR, and apparent diffusion coefficient), primarily to gain insights into longitudinal radiomic changes from preoperative MRI to recurrence and subsequently to predict the region of relapse from 143 ± 42 days before recurrence using machine learning. T1CE MRI first‐order and gray‐level co‐occurrence matrix features are crucial in detecting local recurrence, while multimodal gray‐level difference matrix and first‐order features are highly predictive of the distant relapse, with a voxelwise test accuracy of 80.1% for distant recurrence and 71.4% for local recurrence. In summary, our work exemplifies a step forward in predicting glioblastoma recurrence using radiomics‐based phenotypic changes that may potentially serve as MR‐based biomarkers for customized therapeutic intervention.

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