Large-Scale Multi-Center CT and MRI Segmentation of Pancreas with Deep Learning

Automated volumetric segmentation of the pancreas on cross-sectional imaging is needed for diagnosis and follow-up of pancreatic diseases. While CT-based pancreatic segmentation is more established, MRI-based segmentation methods are understudied, largely due to a lack of publicly available datasets, benchmarking research efforts, and domain-specific deep learning methods. In this retrospective study, we collected a large dataset (767 scans from 499 participants) of T1-weighted (T1W) and T2-weighted (T2W) abdominal MRI series from five centers between March 2004 and November 2022. We also collected CT scans of 1,350 patients from publicly available sources for benchmarking purposes. We developed a new pancreas segmentation method, called PanSegNet, combining the strengths of nnUNet and a Transformer network with a new linear attention module enabling volumetric computation. We tested PanSegNet's accuracy in cross-modality (a total of 2,117 scans) and cross-center settings with Dice and Hausdorff distance (HD95) evaluation metrics. We used Cohen's kappa statistics for intra and inter-rater agreement evaluation and paired t-tests for volume and Dice comparisons, respectively. For segmentation accuracy, we achieved Dice coefficients of 88.3% (std: 7.2%, at case level) with CT, 85.0% (std: 7.9%) with T1W MRI, and 86.3% (std: 6.4%) with T2W MRI. There was a high correlation for pancreas volume prediction with R^2 of 0.91, 0.84, and 0.85 for CT, T1W, and T2W, respectively. We found moderate inter-observer (0.624 and 0.638 for T1W and T2W MRI, respectively) and high intra-observer agreement scores. All MRI data is made available at https://osf.io/kysnj/. Our source code is available at https://github.com/NUBagciLab/PaNSegNet.

ResNCT: A Deep Learning Model for the Synthesis of Nephrographic Phase Images in CT Urography

Purpose: To develop and evaluate a transformer-based deep learning model for the synthesis of nephrographic phase images in CT urography (CTU) examinations from the unenhanced and urographic phases. Materials and Methods: This retrospective study was approved by the local Institutional Review Board. A dataset of 119 patients (mean $\pm$ SD age, 65 $\pm$ 12 years; 75/44 males/females) with three-phase CT urography studies was curated for deep learning model development. The three phases for each patient were aligned with an affine registration algorithm. A custom model, coined Residual transformer model for Nephrographic phase CT image synthesis (ResNCT), was developed and implemented with paired inputs of non-contrast and urographic sets of images trained to produce the nephrographic phase images, that were compared with the corresponding ground truth nephrographic phase images. The synthesized images were evaluated with multiple performance metrics, including peak signal to noise ratio (PSNR), structural similarity index (SSIM), normalized cross correlation coefficient (NCC), mean absolute error (MAE), and root mean squared error (RMSE). Results: The ResNCT model successfully generated synthetic nephrographic images from non-contrast and urographic image inputs. With respect to ground truth nephrographic phase images, the images synthesized by the model achieved high PSNR (27.8 $\pm$ 2.7 dB), SSIM (0.88 $\pm$ 0.05), and NCC (0.98 $\pm$ 0.02), and low MAE (0.02 $\pm$ 0.005) and RMSE (0.042 $\pm$ 0.016). Conclusion: The ResNCT model synthesized nephrographic phase CT images with high similarity to ground truth images. The ResNCT model provides a means of eliminating the acquisition of the nephrographic phase with a resultant 33% reduction in radiation dose for CTU examinations.

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Radiomic Deformation and Textural Heterogeneity (R-DepTH) Descriptor to characterize Tumor Field Effect: Application to Survival Prediction in Glioblastoma

The concept of tumor field effect implies that cancer is a systemic disease with its impact way beyond the visible tumor confines. For instance, in Glioblastoma (GBM), an aggressive brain tumor, the increase in intracranial pressure due to tumor burden often leads to brain herniation and poor outcomes. Our work is based on the rationale that highly aggressive tumors tend to grow uncontrollably, leading to pronounced biomechanical tissue deformations in the normal parenchyma, which when combined with local morphological differences in the tumor confines on MRI scans, will comprehensively capture tumor field effect. Specifically, we present an integrated MRI-based descriptor, radiomic-Deformation and Textural Heterogeneity (r-DepTH). This descriptor comprises measurements of the subtle perturbations in tissue deformations throughout the surrounding normal parenchyma due to mass effect. This involves non-rigidly aligning the patients MRI scans to a healthy atlas via diffeomorphic registration. The resulting inverse mapping is used to obtain the deformation field magnitudes in the normal parenchyma. These measurements are then combined with a 3D texture descriptor, Co-occurrence of Local Anisotropic Gradient Orientations (COLLAGE), which captures the morphological heterogeneity within the tumor confines, on MRI scans. R-DepTH, on N = 207 GBM cases (training set (St) = 128, testing set (Sv) = 79), demonstrated improved prognosis of overall survival by categorizing patients into low- (prolonged survival) and high-risk (poor survival) groups (on St, p-value = 0.0000035, and on Sv, p-value = 0.0024). R-DepTH descriptor may serve as a comprehensive MRI-based prognostic marker of disease aggressiveness and survival in solid tumors.

Spatial-And-Context aware (SpACe) "virtual biopsy" radiogenomic maps to target tumor mutational status on structural MRI

With growing emphasis on personalized cancer-therapies,radiogenomics has shown promise in identifying target tumor mutational status on routine imaging (i.e. MRI) scans. These approaches fall into 2 categories: (1) deep-learning/radiomics (context-based), using image features from the entire tumor to identify the gene mutation status, or (2) atlas (spatial)-based to obtain likelihood of gene mutation status based on population statistics. While many genes (i.e. EGFR, MGMT) are spatially variant, a significant challenge in reliable assessment of gene mutation status on imaging has been the lack of available co-localized ground truth for training the models. We present Spatial-And-Context aware (SpACe) "virtual biopsy" maps that incorporate context-features from co-localized biopsy site along with spatial-priors from population atlases, within a Least Absolute Shrinkage and Selection Operator (LASSO) regression model, to obtain a per-voxel probability of the presence of a mutation status (M+ vs M-). We then use probabilistic pair-wise Markov model to improve the voxel-wise prediction probability. We evaluate the efficacy of SpACe maps on MRI scans with co-localized ground truth obtained from corresponding biopsy, to predict the mutation status of 2 driver genes in Glioblastoma: (1) EGFR (n=91), and (2) MGMT (n=81). When compared against deep-learning (DL) and radiomic models, SpACe maps obtained training and testing accuracies of 90% (n=71) and 90.48% (n=21) in identifying EGFR amplification status,compared to 80% and 71.4% via radiomics, and 74.28% and 65.5% via DL. For MGMT status, training and testing accuracies using SpACe were 88.3% (n=61) and 71.5% (n=20), compared to 52.4% and 66.7% using radiomics,and 79.3% and 68.4% using DL. Following validation,SpACe maps could provide surgical navigation to improve localization of sampling sites for targeting of specific driver genes in cancer.

Can tumor location on pre-treatment MRI predict likelihood of pseudo-progression versus tumor recurrence in Glioblastoma? A feasibility study

A significant challenge in Glioblastoma (GBM) management is identifying pseudo-progression (PsP), a benign radiation-induced effect, from tumor recurrence, on routine imaging following conventional treatment. Previous studies have linked tumor lobar presence and laterality to GBM outcomes, suggesting that disease etiology and progression in GBM may be impacted by tumor location. Hence, in this feasibility study, we seek to investigate the following question: Can tumor location on treatment-na\"ive MRI provide early cues regarding likelihood of a patient developing pseudo-progression versus tumor recurrence? In this study, 74 pre-treatment Glioblastoma MRI scans with PsP (33) and tumor recurrence (41) were analyzed. First, enhancing lesion on Gd-T1w MRI and peri-lesional hyperintensities on T2w/FLAIR were segmented by experts and then registered to a brain atlas. Using patients from the two phenotypes, we construct two atlases by quantifying frequency of occurrence of enhancing lesion and peri-lesion hyperintensities, by averaging voxel intensities across the population. Analysis of differential involvement was then performed to compute voxel-wise significant differences (p-value<0.05) across the atlases. Statistically significant clusters were finally mapped to a structural atlas to provide anatomic localization of their location. Our results demonstrate that patients with tumor recurrence showed prominence of their initial tumor in the parietal lobe, while patients with PsP showed a multi-focal distribution of the initial tumor in the frontal and temporal lobes, insula, and putamen. These preliminary results suggest that lateralization of pre-treatment lesions towards certain anatomical areas of the brain may allow to provide early cues regarding assessing likelihood of occurrence of pseudo-progression from tumor recurrence on MRI scans.

MRQy: An Open-Source Tool for Quality Control of MR Imaging Data

Even as public data repositories such as The Cancer Imaging Archive (TCIA) have enabled development of new radiomics and machine learning schemes, a key concern remains the generalizability of these methods to unseen datasets. For MRI datasets, model performance could be impacted by (a) site- or scanner-specific variations in image resolution, field-of-view, or image contrast, or (b) presence of imaging artifacts such as noise, motion, inhomogeneity, ringing, or aliasing; which can adversely affect relative image quality between data cohorts. This indicates a need for a quantitative tool to quickly determine relative differences in MRI volumes both within and between large data cohorts. We present MRQy, a new open-source quality control tool to (a) interrogate MRI cohorts for site- or equipment-based differences, and (b) quantify the impact of MRI artifacts on relative image quality; to help determine how to correct for these variations prior to model development. MRQy extracts a series of quality measures (e.g. noise ratios, variation metrics, entropy and energy criteria) and MR image metadata (e.g. voxel resolution, image dimensions) for subsequent interrogation via a specialized HTML5 based front-end designed for real-time filtering and trend visualization. MRQy is designed to be a standalone, unsupervised tool that can be efficiently run on a standard desktop computer. It has been made freely accessible at http://github.com/ccipd/MRQy for wider community use and feedback. MRQy was used to evaluate (a) n=133 brain MRIs from TCIA (7 sites), and (b) n=104 rectal MRIs (3 local sites). MRQy measures revealed significant site-specific variations in both cohorts, indicating potential batch effects. Marked differences in specific MRQy measures were also able to identify MRI datasets that needed to be corrected for common MR imaging artifacts.