Search

Glioblastoma is the most common malignant brain tumor with less than 15 months median survival. To aid prognosis, there is a need for decision tools that leverage diagnostic modalities such as MRI to inform survival. In this study, we examine higher-order spatial proximity characteristics from habitats and propose two graph-based methods (minimum spanning tree and graph run-length matrix) to characterize spatial heterogeneity over tumor MRI-derived intensity habitats and assess their relationships with overall survival as well as the immune signature status of patients with glioblastoma. A data set of 74 patients was studied based on the availability of post-contrast T1-weighted and T2-weighted fluid attenuated inversion recovery (FLAIR) image data in The Cancer Image Archive (TCIA). We assessed the predictive value of MST- and GRLM-derived features from 2D images for prediction of 12-month survival status and immune signature status of patients with glioblastoma via a receiver operating characteristic curve analysis. For 12-month survival prediction using MST-based method, sensitivity and specificity were 0.82 and 0.79 respectively. For GRLM-based method, sensitivity and specificity were 0.73 and 0.77 respectively. For immune status, sensitivity and specificity were 0.91 and 0.69, respectively, for the GRLM-based method with an immune effector. Our results show that the proposed MST- and GRLM-derived features are predictive of 12-month survival status as well as the immune signature status of patients with glioblastoma. To our knowledge, this is the first application of MST- and GRLM-based proximity analyses for the study of radiologically-defined tumor habitats in glioblastoma., (© 2023. Springer Nature Limited.)

Differentiating pseudoprogression from true tumor progression has become a significant challenge in follow-up of diffuse infiltrating gliomas, particularly high grade, which leads to a potential treatment delay for patients with early glioma recurrence. In this study, we proposed to use a multiparametric MRI data as a sequence input for the convolutional neural network with the recurrent neural network based deep learning structure to discriminate between pseudoprogression and true tumor progression. In this study, 43 biopsy-proven patient data identified as diffuse infiltrating glioma patients whose disease progressed/recurred were used. The dataset consists of five original MRI sequences; pre-contrast T1-weighted, post-contrast T1-weighted, T2-weighted, FLAIR, and ADC images as well as two engineered sequences; T1post-T1pre and T2-FLAIR. Next, we used three CNN-LSTM models with a different set of sequences as input sequences to pass through CNN-LSTM layers. We performed threefold cross-validation in the training dataset and generated the boxplot, accuracy, and ROC curve, AUC from each trained model with the test dataset to evaluate models. The mean accuracy for VGG16 models ranged from 0.44 to 0.60 and the mean AUC ranged from 0.47 to 0.59. For CNN-LSTM model, the mean accuracy ranged from 0.62 to 0.75 and the mean AUC ranged from 0.64 to 0.81. The performance of the proposed CNN-LSTM with multiparametric sequence data was found to outperform the popular convolutional CNN with a single MRI sequence. In conclusion, incorporating all available MRI sequences into a sequence input for a CNN-LSTM model improved diagnostic performance for discriminating between pseudoprogression and true tumor progression.

Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.

One of the most common and aggressive malignant brain tumors is Glioblastoma multiforme. Despite the multimodality treatment such as radiation therapy and chemotherapy (temozolomide: TMZ), the median survival rate of glioblastoma patient is less than 15 months. In this study, we investigated the association between measures of spatial diversity derived from spatial point pattern analysis of multiparametric magnetic resonance imaging (MRI) data with molecular status as well as 12-month survival in glioblastoma. We obtained 27 measures of spatial proximity (diversity) via spatial point pattern analysis of multiparametric T1 post-contrast and T2 fluid-attenuated inversion recovery MRI data. These measures were used to predict 12-month survival status (≤12 or >12 months) in 74 glioblastoma patients. Kaplan-Meier with receiver operating characteristic analyses was used to assess the relationship between derived spatial features and 12-month survival status as well as molecular subtype status in patients with glioblastoma. Kaplan-Meier survival analysis revealed that 14 spatial features were capable of stratifying overall survival in a statistically significant manner. For prediction of 12-month survival status based on these diversity indices, sensitivity and specificity were 0.86 and 0.64, respectively. The area under the receiver operating characteristic curve and the accuracy were 0.76 and 0.75, respectively. For prediction of molecular subtype status, proneural subtype shows highest accuracy of 0.93 among all molecular subtypes based on receiver operating characteristic analysis. We find that measures of spatial diversity from point pattern analysis of intensity habitats from T1 post-contrast and T2 fluid-attenuated inversion recovery images are associated with both tumor subtype status and 12-month survival status and may therefore be useful indicators of patient prognosis, in addition to providing potential guidance for molecularly-targeted therapies in Glioblastoma multiforme.

This study compared three methods for analyzing DCE-MRI data with a reference region (RR) model: a linear least-square fitting with numerical analysis (LLSQ-N), a nonlinear least-square fitting with numerical analysis (NLSQ-N), and an analytical analysis (NLSQ-A). The accuracy and precision of estimating the pharmacokinetic parameter ratios KR and VR, where KR is defined as a ratio between the two volume transfer constants, K(trans,TOI) and K(trans,RR), and VR is the ratio between the two extracellular extravascular volumes, ve,TOI and ve,RR, were assessed using simulations under various signal-to-noise ratios (SNRs) and temporal resolutions (4, 6, 30, and 60s). When no noise was added, the simulations showed that the mean percent error (MPE) for the estimated KR and VR using the LLSQ-N and NLSQ-N methods ranged from 1.2% to 31.6% with various temporal resolutions while the NLSQ-A method maintained a very high accuracy (<1.0×10(-4) %) regardless of the temporal resolution. The simulation also indicated that the LLSQ-N and NLSQ-N methods appear to underestimate the parameter ratios more than the NLSQ-A method. In addition, seven in vivo DCE-MRI datasets from spontaneously occurring canine brain tumors were analyzed with each method. Results for the in vivo study showed that KR (ranging from 0.63 to 3.11) and VR (ranging from 2.82 to 19.16) for the NLSQ-A method were both higher than results for the other two methods (KR ranging from 0.01 to 1.29 and VR ranging from 1.48 to 19.59). A temporal downsampling experiment showed that the averaged percent error for the NLSQ-A method (8.45%) was lower than the other two methods (22.97% for LLSQ-N and 65.02% for NLSQ-N) for KR, and the averaged percent error for the NLSQ-A method (6.33%) was lower than the other two methods (6.57% for LLSQ-N and 13.66% for NLSQ-N) for VR. Using simulations, we showed that the NLSQ-A method can estimate the ratios of pharmacokinetic parameters more accurately and precisely than the NLSQ-N and LLSQ-N methods over various SNRs and temporal resolutions. All simulations were validated with in vivo DCE MRI data., (Copyright © 2014 Elsevier Inc. All rights reserved.)