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  • 1
    In: Neoplasia, Elsevier BV, Vol. 36 ( 2023-02), p. 100869-
    Type of Medium: Online Resource
    ISSN: 1476-5586
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2008231-9
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  • 2
    In: The Neuroradiology Journal, SAGE Publications, Vol. 32, No. 2 ( 2019-04), p. 74-85
    Abstract: The purpose of this study was to determine the accuracy of selected first or second-order histogram features in differentiation of functional types of pituitary macro-adenomas. Materials and methods Diffusion-weighted imaging magnetic resonance imaging was performed on 32 patients (age mean±standard deviation = 43.09 ± 11.02 years; min = 22 and max = 65 years) with pituitary macro-adenoma (10 with functional and 22 with non-functional tumors). Histograms of apparent diffusion coefficient were generated from regions of interest and selected first or second-order histogram features were extracted. Collagen contents of the surgically resected tumors were examined histochemically using Masson trichromatic staining and graded as containing 〈 1%, 1–3%, and 〉 3% of collagen. Results Among selected first or second-order histogram features, uniformity ( p = 0.02), 75th percentile ( p = 0.03), and tumor smoothness ( p = 0.02) were significantly different between functional and non-functional tumors. Tumor smoothness  〉  5.7 × 10 −9 (area under the curve = 0.75; 0.56–0.89) had 70% (95% confidence interval = 34.8–93.3%) sensitivity and 33.33% (95% confidence interval = 14.6–57.0%) specificity for diagnosis of functional tumors. Uniformity ≤179.271 had a sensitivity of 60% (95% confidence interval = 26.2–87.8%) and specificity of 90.48% (95% confidence interval = 69.6–98.8%) with area under the curve = 0.76; 0.57–0.89. The 75th percentile 〉 0.7 had a sensitivity of 80% (95% confidence interval = 44.4–97.5%) and specificity of 66.67% (95% confidence interval = 43.0–85.4%) for categorizing tumors to functional and non-functional types (area under the curve = 0.74; 0.55–0.88). Using these cut-offs, smoothness and uniformity are suggested as negative predictive indices (non-functional tumors) whereas 75th percentile is more applicable for diagnosis of functional tumors. Conclusion First or second-order histogram features could be helpful in differentiating functional vs non-functional pituitary macro-adenoma tumors.
    Type of Medium: Online Resource
    ISSN: 1971-4009 , 2385-1996
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2622347-8
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  • 3
    In: npj Precision Oncology, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2023-06-19)
    Abstract: Increasing evidence suggests that besides mutational and molecular alterations, the immune component of the tumor microenvironment also substantially impacts tumor behavior and complicates treatment response, particularly to immunotherapies. Although the standard method for characterizing tumor immune profile is through performing integrated genomic analysis on tissue biopsies, the dynamic change in the immune composition of the tumor microenvironment makes this approach not feasible, especially for brain tumors. Radiomics is a rapidly growing field that uses advanced imaging techniques and computational algorithms to extract numerous quantitative features from medical images. Recent advances in machine learning methods are facilitating biological validation of radiomic signatures and allowing them to “mine” for a variety of significant correlates, including genetic, immunologic, and histologic data. Radiomics has the potential to be used as a non-invasive approach to predict the presence and density of immune cells within the microenvironment, as well as to assess the expression of immune-related genes and pathways. This information can be essential for patient stratification, informing treatment decisions and predicting patients’ response to immunotherapies. This is particularly important for tumors with difficult surgical access such as gliomas. In this review, we provide an overview of the glioma microenvironment, describe novel approaches for clustering patients based on their tumor immune profile, and discuss the latest progress on utilization of radiomics for immune profiling of glioma based on current literature.
    Type of Medium: Online Resource
    ISSN: 2397-768X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2891458-2
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  • 4
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii166-vii166
    Abstract: There is evidence that molecular heterogeneity of glioblastoma is associated with heterogeneity of MR imaging signatures. Modern machine learning models, such as deep neural networks, provide a tool for capturing such complex relationships in high-dimensional datasets. This study leverages recent advances in visualizing neural networks to construct a radiogenomics coordinate system whose axes reflect the expression of imaging signatures of genetic mutations commonly found in glioblastoma. METHODS Multi-parametric MRI (mpMRI) scans (T1, T1-Gd, T2, T2-FLAIR, DSC, DTI) of 254 subjects with glioblastoma were retrospectively collected. Radiomics features, including histograms, morphologic and textural descriptors, were derived. Genetic markers were obtained through next generation sequencing (NGS) panel. A multi-label classification deep neural network was trained for predicting mutation status in key driver genes, EGFR, PTEN, NF1, TP53 and RB1. We utilized a nonlinear manifold learning method called Intensive Principal Component Analysis (InPCA), to visualize the output probability distributions from the trained model. The first three principal components (PCs) were selected for constructing the coordinate system. RESULTS The axes derived from InPCA analysis were associated with molecular pathways known to be implicated in glioblastoma: (1) Increasing values of PC1 were associated with primary involvement of P53 then RB1 then MAPK then RTK/PI3K; (2) Increasing values of PC2 were associated with primary involvement of RTK then RB1/P53/MAPK then PI3K; (3) Increasing values of PC3 were associated with primary involvement of MAPK then RB1/P53/RTK/PI3K. Imaging features significantly associated with each of three PCs (p & lt; 0.05) were identified by Pearson correlation analysis. CONCLUSION Deep learning followed by nonlinear manifold embedding identifies a radiogenomics coordinate system spanned by three components which were associated with different molecular pathways of glioblastoma. The heterogeneity of radiogenomic signatures captured by this coordinate system offers in vivo biomarkers of the molecular heterogeneity of glioblastoma.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 5
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_1 ( 2023-06-12), p. i47-i48
    Abstract: In pediatric low-grade gliomas (pLGG), prognosis and responses to treatments are heterogeneous. This heterogeneity may be explained by the differences in molecular composition of the tumors of the same histology and the likely upstream alterations following administered radiation or systemic therapy. Integration of radiomics and clinical variables could generate a non-invasive biomarker that provides upfront prediction about patient’s risk of progression. We show that our proposed radiomic-based risk-stratification signature for pLGGs is associated with alterations in transcriptomic pathways. Standard multiparametric MRI sequences of 134 pLGG patients from Children’s Brain Tumor Network (CBTN) were retrospectively collected and 881 quantitative radiomic features were extracted. A multivariate Cox proportional hazard’s (Cox-PH) regression model was fitted on clinical (age, sex, tumor location, and extent of tumor resection) along with radiomic variables using 5-fold cross-validation, to predict patient’s risk of progression. The Cox-PH model showed excellent performance in prediction of PFS and patient’s risk scores, supported by the concordance index of 0.78. Radiogenomic analysis was performed to determine the transcriptomic pathways (1594 pathways, c2 MsigDb Reactome v2022.1) that contribute to the pLGG risk, predicted by the radiomic signature. ElasticNet regression was applied on the scores obtained by gene set enrichment analysis (GSEA) (in 70/134 subjects) to predict radiomic-based risk scores. Increased risk, corresponded to upregulation of DNA repair pathways, dysregulation of lipophagy, fatty acid beta oxidation, and vitamin D pathways, which are tumor-promoting. BRAFfusion signaling inversely correlated with risk, consistent with known favorable prognosis of KIAA1549-BRAF fused pLGGs. Upregulation in immune related pathways and Toll-Like Receptor (TLR) signaling was associated with lower risk. This study elucidates the synergistic dynamics between the biological processes that promote the risk of progression and radiomic-based risk-stratification signature. The proposed biomarker may be used to encourage targeted therapies in patients with increased predicted risk.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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  • 6
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_1 ( 2023-06-12), p. i47-i47
    Abstract: Current response assessment in pediatric brain tumors (PBTs), as recommended by the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, relies on 2D measurements of changes in tumor size. However, there is growing evidence of underestimation of tumor size in PBTs using 2D compared to volumetric (3D) measurement approach. Accordingly, automated methods that reduce manual burden and intra- and inter-rater variability in segmenting tumor subregions and volumetric evaluations are warranted to facilitate tumor response assessment of PBTs. We have developed a fully automatic deep learning (DL) model using the nnUNet architecture on a large cohort of multi-institutional and multi-histology PBTs. The model was trained on widely available standard multiparametric MRI sequences (T1-pre, T1-post, T2, T2-FLAIR) for segmentation of the whole tumor and RAPNO-recommended subregions, including enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). As a prerequisite step for accurate tumor segmentation, we also generated another DL model based on DeepMedic for brain extraction from mpMRIs. The models were trained on an institutional cohort of 151 subjects and independently tested on 64 subjects from the internal and 29 patients from external institutions. The trained models showed excellent performance with median Dice scores of 0.98±0.02/0.97±0.02 for brain tissue segmentation, 0.92±0.08/0.90±0.17 for whole tumor segmentation, 0.76±0.31/0.87±0.29 for ET subregion, and 0.82±0.15/0.80±0.28 for segmentation of non-enhancing components (combination of NET, CC, and ED) in internal/external test sets, respectively. The automated segmentation demonstrated strong agreement with expert segmentations in volumetric measurement of tumor components, with Pearson’s correlation coefficients of 0.97, 0.97, 0.99, and 0.79 (p & lt;0.0001) for ET, NET, CC, and ED regions, respectively. Our proposed multi-institutional and multi-histology automated segmentation method has the potential to aid clinical neuro-oncology practice by providing reliable and reproducible volumetric measurements for treatment response assessment.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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  • 7
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi137-vi137
    Abstract: Multi-parametric MRI based radiomic signatures have highlighted the promise of artificial intelligence (AI) in neuro-oncology. However, inter-institution heterogeneity hinders generalization to data from unseen clinical institutions. To this end, we formulated the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium for glioblastoma. Here, we seek non-invasive generalizable radiomic signatures from routine clinically-acquired MRI for prognostic stratification of glioblastoma patients. METHODS We identified a retrospective cohort of 606 patients with near/gross total tumor resection ( & gt;90%), from 13 geographically-diverse institutions. All pre-operative structural MRI scans (T1,T1-Gd,T2,T2-FLAIR) were aligned to a common anatomical atlas. An automatic algorithm segmented the whole tumors (WTs) into 3 sub-compartments, i.e., enhancing (ET), necrotic core (NC), and peritumoral T2-FLAIR signal abnormality (ED). The combination of ET+NC defines the tumor core (TC). Quantitative radiomic features were extracted to generate our AI model to stratify patients into short- ( & lt; 14mts) and long-survivors ( & gt;14mts). The model trained on 276 patients from a single institution was independently validated on 330 unseen patients from 12 left-out institutions, using the area-under-the-receiver-operating-characteristic-curve (AUC). RESULTS Each feature individually offered certain (limited but reproducible) value for identifying short-survivors: 1) TC closer to lateral ventricles (AUC=0.62); 2) larger ET/brain (AUC=0.61); 3) larger TC/brain (AUC=0.59); 4) larger WT/brain (AUC=0.55); 5) larger ET/WT (AUC=0.59); 6) smaller ED/WT (AUC=0.57); 7) larger ventricle deformations (AUC=0.6). Integrating all features and age, through a multivariate AI model, resulted in higher accuracy (AUC=0.7; 95% C.I.,0.64-0.77). CONCLUSION Prognostic stratification using basic radiomic features is highly reproducible across diverse institutions and patient populations. Multivariate integration yields relatively more accurate and generalizable radiomic signatures, across institutions. Our results offer promise for generalizable non-invasive in vivo signatures of survival prediction in patients with glioblastoma. Extracted features from clinically-acquired imaging, renders these signatures easier for clinical translation. Large-scale evaluation could contribute to improving patient management and treatment planning. *Indicates equal authorship.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2094060-9
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  • 8
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi134-vi135
    Abstract: Decision making about the best course of treatment for glioblastoma patients becomes challenging when a new enhancing lesion appears in the vicinity of the surgical bed on follow-up MRI (after maximal safe tumor resection and chemoradiation), raising concerns for tumor progression (TP). Literature indicates 30-50% of these new lesions describe primarily treatment-related changes (TRC). We hypothesize that quantitative analysis of specific and sensitive features extracted from multi-parametric MRI (mpMRI) via machine learning (ML) techniques may yield non-invasive imaging signatures that distinguish TP from TRC and facilitate better treatment personalization. METHODS We have generated an ML model on a retrospective cohort of 58 subjects, and prospectively evaluated on an independent cohort of 58 previously unseen patients who underwent second resection for suspicious recurrence and had availability of advanced mpMRI (T1, T1-Gd, T2, T2-FLAIR, DTI, DSC). The features selected by our retrospective model, representing principal components analysis of intensity distributions, morphological, statistical, and texture descriptors, were extracted from the mpMRI of the prospective cohort. Integration of these features revealed signatures distinguishing between TP, mixed response, and TRC. Independently, a board-certified neuropathologist evaluated the resected tissue by blindly classifying it in the above three categories, based on mitotic figures, pseudopalisading necrosis, geographic necrosis, dystrophic calcification, vascular changes, and Ki67. RESULTS Tissues classified as TRC by the neuropathologist were associated with imaging phenotypes of lower angiogenesis (DSC-derived features), lower cellularity (DTI-derived features), and higher water concentration (T2, T2-FLAIR features). Our ML model characterized TP with 78% accuracy (sensitivity:86%, specificity:70%, AUC:0.80 (95%CI, 0.68-0.92)) and TRC with 81% accuracy (sensitivity:80%, specificity:81%, AUC:0.87 (95%CI, 0.72-1.00)). CONCLUSION Our proposed ML model reveals distinct non-invasive markers of TP and TRC, directly associated with histopathological changes in prospective glioblastoma patients. Reliable stratification of TP and TRC entities may help to noninvasively determine whether the course of treatment should change.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2094060-9
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  • 9
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii185-vii185
    Abstract: Recent studies have shown preliminary evidence for differentiation of the tumor microenvironment (TME) and immune landscape between molecularly-defined medulloblastoma (MB) subtypes. Identifying radiological correlates of these TME patterns could establish a non-invasive method of immune profile characterization for guiding patient-centered therapies. Here, we examine immune profiles between MB subtypes using data from Open Pediatric Brain Tumor Atlas (OpenPBTA), and their relationship to tumor measurements from pre-operative MRIs. We identified a retrospective cohort of 94 pediatric MB patients with available molecular subtyping and immune profiles (36 cell types) from bulk gene expression data. A random forest analysis was used to classify the four MB subtypes based on immune profiles. Four cell types had high impact on classification performance: plasmacytoid dendritic cells (PDC; 25.8% accuracy decrease when randomized), hematopoietic stem cells (HSC; 21.9%), plasma B cells (20.3%), and cancer associated fibroblasts (18.8%). Pairwise comparisons revealed SHH and WNT tumors had significantly higher numbers of fibroblasts and HSCs compared to Group3/Group4. We also found novel evidence for significantly lower amounts of plasma B cells in the SHH group, and high PDC levels in Group4, followed by Group3, and low PDC in SHH/WNT. Multi-parametric MRI scans for 39 patients were used to segment tumor volumes. Overall tumor volume was significantly correlated with composite stroma scores (R = 0.34, p = 0.036). Additionally, patients with higher volumes of gadolinium contrast-enhancing compared to non-enhancing components had higher immune (R = 0.42, p = 0.009) and microenvironment (summed immune and stromal cell types; R = 0.44, p = 0.006) scores, regardless of their molecular subtype. Together, our results demonstrate: (1) the use of rich immune profiles for differentiating molecular subtypes of MB and their unique TME characterization; and (2) initial evidence for radiological correlates of these profiles based on pre-operative imaging collected through standard practices.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 10
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii170-vii170
    Abstract: Glioblastoma, IDH-wildtype, is the most common primary malignant adult brain tumor with median overall survival (OS) of ~14 months, with little improvement over the last 20 years. We hypothesize that AI-based integration of quantitative tumor characteristics, independent of acquisition protocol and equipment, can reveal accurate generalizable prognostic stratification. We seek an AI-based OS predictor using routine clinically acquired MRI sequences, quantitatively evaluated across institutions of the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium. METHODS We identified a retrospective cohort of 2,293 diffuse glioma (IDH-wildtype/-NOS/-NEC) patients from 22 geographically distinct institutions across 3 continents, with preoperative structural MRI scans. The entire tumor burden was automatically segmented into 3 sub-compartments, i.e., enhancing, necrotic, peritumoral T2-FLAIR abnormality. We developed our AI predictor by multivariate integration of i)patient age, ii)tumor sub-compartment volume normalized to brain volume, iii)spatial distribution characteristics (tumor location, distance to the ventricles, and laterality), and iv)morphologic descriptors (major axes’ length, axes’ ratio, extent, and number of tumors). The AI predictor returns a continuous value between 0-1, defining short-, intermediate-, and long-survivors based on thresholds on the 25th and 75th percentiles. Leave-One-Site-Out-Cross-Validation was used to assess the generalizability of our stratification. Kaplan-Meier survival curves were computed for OS analysis and evaluated by a Cox proportional hazards model for statistical significance and hazard ratios. RESULTS Survival analysis yielded a hazard ratio of 2.07 (95%CI, 2.06-2.08, p-value= 4.8e-102) for patient stratification into short-, intermediate-, and long-survivors. Pearson correlation between the predicted and actual OS yielded an R= 0.49. CONCLUSION Multivariate integration of visually quantified tumor characteristics, agnostic to acquisition protocol/equipment, yields an accurate OS surrogate index. Validation of our AI model in the largest centralized glioblastoma imaging dataset, from the ReSPOND consortium, supports its generalizability across diverse patient populations and acquisition settings, potentially contributing to equitable improvements of personalized patient care.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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