Weakly Supervised Skull Stripping of Magnetic Resonance Imaging of Brain Tumor Patients.

Automatic brain tumor segmentation is particularly challenging on magnetic resonance imaging (MRI) with marked pathologies, such as brain tumors, which usually cause large displacement, abnormal appearance, and deformation of brain tissue. Despite an abundance of previous literature on learning-based methodologies for MRI segmentation, few works have focused on tackling MRI skull stripping of brain tumor patient data. This gap in literature can be associated with the lack of publicly available data (due to concerns about patient identification) and the labor-intensive nature of generating ground truth labels for model training. In this retrospective study, we assessed the performance of Dense-Vnet in skull stripping brain tumor patient MRI trained on our large multi-institutional brain tumor patient dataset. Our data included pretreatment MRI of 668 patients from our in-house institutional review board-approved multi-institutional brain tumor repository. Because of the absence of ground truth, we used imperfect automatically generated training labels using SPM12 software. We trained the network using common MRI sequences in oncology: T1-weighted with gadolinium contrast, T2-weighted fluid-attenuated inversion recovery, or both. We measured model performance against 30 independent brain tumor test cases with available manual brain masks. All images were harmonized for voxel spacing and volumetric dimensions before model training. Model training was performed using the modularly structured deep learning platform NiftyNet that is tailored toward simplifying medical image analysis. Our proposed approach showed the success of a weakly supervised deep learning approach in MRI brain extraction even in the presence of pathology. Our best model achieved an average Dice score, sensitivity, and specificity of, respectively, 94.5, 96.4, and 98.5% on the multi-institutional independent brain tumor test set. To further contextualize our results within existing literature on healthy brain segmentation, we tested the model against healthy subjects from the benchmark LBPA40 dataset. For this dataset, the model achieved an average Dice score, sensitivity, and specificity of 96.2, 96.6, and 99.2%, which are, although comparable to other publications, slightly lower than the performance of models trained on healthy patients. We associate this drop in performance with the use of brain tumor data for model training and its influence on brain appearance.

Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment With Standard-of-Care.

Glioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) (N = 184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established (N = 40 with SOC, N = 19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM (N = 144 with SOC, N = 111 without SOC). When stratified by sex, the survival benefit of cystic GBM was only preserved in male patients (N = 303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.

Deep neural network to locate and segment brain tumors outperformed the expert technicians who created the training data.

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data.

Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies.

BACKGROUND: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. METHODS: DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. RESULTS: In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. CONCLUSION: DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients.

BACKGROUND: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. METHODS: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). RESULTS: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test). CONCLUSION: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

A Deep Convolutional Neural Network for Annotation of Magnetic Resonance Imaging Sequence Type.

The explosion of medical imaging data along with the advent of big data analytics has launched an exciting era for clinical research. One factor affecting the ability to aggregate large medical image collections for research is the lack of infrastructure for automated data annotation. Among all imaging modalities, annotation of magnetic resonance (MR) images is particularly challenging due to the non-standard labeling of MR image types. In this work, we aimed to train a deep neural network to annotate MR image sequence type for scans of brain tumor patients. We focused on the four most common MR sequence types within neuroimaging: T1-weighted (T1W), T1-weighted post-gadolinium contrast (T1Gd), T2-weighted (T2W), and T2-weighted fluid-attenuated inversion recovery (FLAIR). Our repository contains images acquired using a variety of pulse sequences, sequence parameters, field strengths, and scanner manufacturers. Image selection was agnostic to patient demographics, diagnosis, and the presence of tumor in the imaging field of view. We used a total of 14,400 two-dimensional images, each visualizing a different part of the brain. Data was split into train, validation, and test sets (9600, 2400, and 2400 images, respectively) and sets consisted of equal-sized groups of image types. Overall, the model reached an accuracy of 99% on the test set. Our results showed excellent performance of deep learning techniques in predicting sequence types for brain tumor MR images. We conclude deep learning models can serve as tools to support clinical research and facilitate efficient database management.