Early prognostication of overall survival for pediatric diffuse midline gliomas using MRI radiomics and machine learning: A two-center study.

Background: Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors that are diagnosed and monitored through MRI. We developed an automatic pipeline to segment subregions of DMG and select radiomic features that predict patient overall survival (OS). Methods: We acquired diagnostic and post-radiation therapy (RT) multisequence MRI (T1, T1ce, T2, and T2 FLAIR) and manual segmentations from 2 centers: 53 from 1 center formed the internal cohort and 16 from the other center formed the external cohort. We pretrained a deep learning model on a public adult brain tumor data set (BraTS 2021), and finetuned it to automatically segment tumor core (TC) and whole tumor (WT) volumes. PyRadiomics and sequential feature selection were used for feature extraction and selection based on the segmented volumes. Two machine learning models were trained on our internal cohort to predict patient 12-month survival from diagnosis. One model used only data obtained at diagnosis prior to any therapy (baseline study) and the other used data at both diagnosis and post-RT (post-RT study). Results: Overall survival prediction accuracy was 77% and 81% for the baseline study, and 85% and 78% for the post-RT study, for internal and external cohorts, respectively. Homogeneous WT intensity in baseline T2 FLAIR and larger post-RT TC/WT volume ratio indicate shorter OS. Conclusions: Machine learning analysis of MRI radiomics has potential to accurately and noninvasively predict which pediatric patients with DMG will survive less than 12 months from the time of diagnosis to provide patient stratification and guide therapy.

Comparison of Volumetric and 2D Measurements and Longitudinal Trajectories in the Response Assessment of BRAF V600E-Mutant Pediatric Gliomas in the Pacific Pediatric Neuro-Oncology Consortium Clinical Trial.

BACKGROUND AND PURPOSE: Response on imaging is widely used to evaluate treatment efficacy in clinical trials of pediatric gliomas. While conventional criteria rely on 2D measurements, volumetric analysis may provide a more comprehensive response assessment. There is sparse research on the role of volumetrics in pediatric gliomas. Our purpose was to compare 2D and volumetric analysis with the assessment of neuroradiologists using the Brain Tumor Reporting and Data System (BT-RADS) in BRAF V600E-mutant pediatric gliomas. MATERIALS AND METHODS: Manual volumetric segmentations of whole and solid tumors were compared with 2D measurements in 31 participants (292 follow-up studies) in the Pacific Pediatric Neuro-Oncology Consortium 002 trial (NCT01748149). Two neuroradiologists evaluated responses using BT-RADS. Receiver operating characteristic analysis compared classification performance of 2D and volumetrics for partial response. Agreement between volumetric and 2D mathematically modeled longitudinal trajectories for 25 participants was determined using the model-estimated time to best response. RESULTS: Of 31 participants, 20 had partial responses according to BT-RADS criteria. Receiver operating characteristic curves for the classification of partial responders at the time of first detection (median = 2 months) yielded an area under the curve of 0.84 (95% CI, 0.69-0.99) for 2D area, 0.91 (95% CI, 0.80-1.00) for whole-volume, and 0.92 (95% CI, 0.82-1.00) for solid volume change. There was no significant difference in the area under the curve between 2D and solid (P = .34) or whole volume (P = .39). There was no significant correlation in model-estimated time to best response (ρ = 0.39, P >.05) between 2D and whole-volume trajectories. Eight of the 25 participants had a difference of ≥90 days in transition from partial response to stable disease between their 2D and whole-volume modeled trajectories. CONCLUSIONS: Although there was no overall difference between volumetrics and 2D in classifying partial response assessment using BT-RADS, further prospective studies will be critical to elucidate how the observed differences in tumor 2D and volumetric trajectories affect clinical decision-making and outcomes in some individuals.

Active Learning in Brain Tumor Segmentation with Uncertainty Sampling and Annotation Redundancy Restriction.

Deep learning models have demonstrated great potential in medical imaging but are limited by the expensive, large volume of annotations required. To address this, we compared different active learning strategies by training models on subsets of the most informative images using real-world clinical datasets for brain tumor segmentation and proposing a framework that minimizes the data needed while maintaining performance. Then, 638 multi-institutional brain tumor magnetic resonance imaging scans were used to train three-dimensional U-net models and compare active learning strategies. Uncertainty estimation techniques including Bayesian estimation with dropout, bootstrapping, and margins sampling were compared to random query. Strategies to avoid annotating similar images were also considered. We determined the minimum data necessary to achieve performance equivalent to the model trained on the full dataset (α = 0.05). Bayesian approximation with dropout at training and testing showed results equivalent to that of the full data model (target) with around 30% of the training data needed by random query to achieve target performance (p = 0.018). Annotation redundancy restriction techniques can reduce the training data needed by random query to achieve target performance by 20%. We investigated various active learning strategies to minimize the annotation burden for three-dimensional brain tumor segmentation. Dropout uncertainty estimation achieved target performance with the least annotated data.

Physics-Informed Discretization for Reproducible and Robust Radiomic Feature Extraction Using Quantitative MRI.

OBJECTIVE: Given the limited repeatability and reproducibility of radiomic features derived from weighted magnetic resonance imaging (MRI), there may be significant advantages to using radiomics in conjunction with quantitative MRI. This study introduces a novel physics-informed discretization (PID) method for reproducible radiomic feature extraction and evaluates its performance using quantitative MRI sequences including magnetic resonance fingerprinting (MRF) and apparent diffusion coefficient (ADC) mapping. MATERIALS AND METHODS: A multiscanner, scan-rescan dataset comprising whole-brain 3D quantitative (MRF T1, MRF T2, and ADC) and weighted MRI (T1w MPRAGE, T2w SPACE, and T2w FLAIR) from 5 healthy subjects was prospectively acquired. Subjects underwent 2 repeated acquisitions on 3 distinct 3 T scanners each, for a total of 6 scans per subject (30 total scans). First-order statistical (n = 23) and second-order texture (n = 74) radiomic features were extracted from 56 brain tissue regions of interest using the proposed PID method (for quantitative MRI) and conventional fixed bin number (FBN) discretization (for quantitative MRI and weighted MRI). Interscanner radiomic feature reproducibility was measured using the intraclass correlation coefficient (ICC), and the effect of image sequence (eg, MRF T1 vs T1w MPRAGE), as well as image discretization method (ie, PID vs FBN), on radiomic feature reproducibility was assessed using repeated measures analysis of variance. The robustness of PID and FBN discretization to segmentation error was evaluated by simulating segmentation differences in brainstem regions of interest. Radiomic features with ICCs greater than 0.75 following simulated segmentation were determined to be robust to segmentation. RESULTS: First-order features demonstrated higher reproducibility in quantitative MRI than weighted MRI sequences, with 30% (n = 7/23) features being more reproducible in MRF T1 and MRF T2 than weighted MRI. Gray level co-occurrence matrix (GLCM) texture features extracted from MRF T1 and MRF T2 were significantly more reproducible using PID compared with FBN discretization; for all quantitative MRI sequences, PID yielded the highest number of texture features with excellent reproducibility (ICC > 0.9). Comparing texture reproducibility of quantitative and weighted MRI, a greater proportion of MRF T1 (n = 225/370, 61%) and MRF T2 (n = 150/370, 41%) texture features had excellent reproducibility (ICC > 0.9) compared with T1w MPRAGE (n = 148/370, 40%), ADC (n = 115/370, 32%), T2w SPACE (n = 98/370, 27%), and FLAIR (n = 102/370, 28%). Physics-informed discretization was also more robust than FBN discretization to segmentation error, as 46% (n = 103/222, 46%) of texture features extracted from quantitative MRI using PID were robust to simulated 6 mm segmentation shift compared with 19% (n = 42/222, 19%) of weighted MRI texture features extracted using FBN discretization. CONCLUSIONS: The proposed PID method yields radiomic features extracted from quantitative MRI sequences that are more reproducible and robust than radiomic features extracted from weighted MRI using conventional (FBN) discretization approaches. Quantitative MRI sequences also demonstrated greater scan-rescan robustness and first-order feature reproducibility than weighted MRI.

Early prognostication of overall survival for pediatric diffuse midline gliomas using MRI radiomics and machine learning: a two-center study.

Background: Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors that are diagnosed and monitored through MRI. We developed an automatic pipeline to segment subregions of DMG and select radiomic features that predict patient overall survival (OS). Methods: We acquired diagnostic and post-radiation therapy (RT) multisequence MRI (T1, T1ce, T2, T2 FLAIR) and manual segmentations from two centers of 53 (internal cohort) and 16 (external cohort) DMG patients. We pretrained a deep learning model on a public adult brain tumor dataset, and finetuned it to automatically segment tumor core (TC) and whole tumor (WT) volumes. PyRadiomics and sequential feature selection were used for feature extraction and selection based on the segmented volumes. Two machine learning models were trained on our internal cohort to predict patient 1-year survival from diagnosis. One model used only diagnostic tumor features and the other used both diagnostic and post-RT features. Results: For segmentation, Dice score (mean [median]±SD) was 0.91 (0.94)±0.12 and 0.74 (0.83)±0.32 for TC, and 0.88 (0.91)±0.07 and 0.86 (0.89)±0.06 for WT for internal and external cohorts, respectively. For OS prediction, accuracy was 77% and 81% at time of diagnosis, and 85% and 78% post-RT for internal and external cohorts, respectively. Homogeneous WT intensity in baseline T2 FLAIR and larger post-RT TC/WT volume ratio indicate shorter OS. Conclusions: Machine learning analysis of MRI radiomics has potential to accurately and non-invasively predict which pediatric patients with DMG will survive less than one year from the time of diagnosis to provide patient stratification and guide therapy.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs).

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets. To address this unmet need, we provide a multi-institutional, large-scale pediatric dataset of 23,101 multi-parametric MRI exams acquired through routine care for 1,526 brain tumor patients, as part of the Children's Brain Tumor Network. This includes longitudinal MRIs across various cancer diagnoses, with associated patient-level clinical information, digital pathology slides, as well as tissue genotype and omics data. To facilitate downstream analysis, treatment-naïve images for 370 subjects were processed and released through the NCI Childhood Cancer Data Initiative via the Cancer Data Service. Through ongoing efforts to continuously build these imaging repositories, our aim is to accelerate discovery and translational AI models with real-world data, to ultimately empower precision medicine for children.

Systematic Literature Review of Machine Learning Algorithms Using Pretherapy Radiologic Imaging for Glioma Molecular Subtype Prediction.

BACKGROUND: The molecular profile of gliomas is a prognostic indicator for survival, driving clinical decision-making for treatment. Pathology-based molecular diagnosis is challenging because of the invasiveness of the procedure, exclusion from neoadjuvant therapy options, and the heterogeneous nature of the tumor. PURPOSE: We performed a systematic review of algorithms that predict molecular subtypes of gliomas from MR Imaging. DATA SOURCES: Data sources were Ovid Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science. STUDY SELECTION: Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 12,318 abstracts were screened and 1323 underwent full-text review, with 85 articles meeting the inclusion criteria. DATA ANALYSIS: We compared prediction results from different machine learning approaches for predicting molecular subtypes of gliomas. Bias analysis was conducted for each study, following the Prediction model Risk Of Bias Assessment Tool (PROBAST) guidelines. DATA SYNTHESIS: Isocitrate dehydrogenase mutation status was reported with an area under the curve and accuracy of 0.88 and 85% in internal validation and 0.86 and 87% in limited external validation data sets, respectively. For the prediction of O6-methylguanine-DNA methyltransferase promoter methylation, the area under the curve and accuracy in internal validation data sets were 0.79 and 77%, and in limited external validation, 0.89 and 83%, respectively. PROBAST scoring demonstrated high bias in all articles. LIMITATIONS: The low number of external validation and studies with incomplete data resulted in unequal data analysis. Comparing the best prediction pipelines of each study may introduce bias. CONCLUSIONS: While the high area under the curve and accuracy for the prediction of molecular subtypes of gliomas are reported in internal and external validation data sets, limited use of external validation and the increased risk of bias in all articles may present obstacles for clinical translation of these techniques.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Brain MR Image Synthesis for Tumor Segmentation (BraSyn).

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.

The ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge 2023: Intracranial Meningioma.

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

Radiomics for characterization of the glioma immune microenvironment.

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.

Current state of pediatric neuro-oncology imaging, challenges and future directions.

Imaging plays a central role in neuro-oncology including primary diagnosis, treatment planning, and surveillance of tumors. The emergence of quantitative imaging and radiomics provided an uprecedented opportunity to compile mineable databases that can be utilized in a variety of applications. In this review, we aim to summarize the current state of conventional and advanced imaging techniques, standardization efforts, fast protocols, contrast and sedation in pediatric neuro-oncologic imaging, radiomics-radiogenomics, multi-omics and molecular imaging approaches. We will also address the existing challenges and discuss future directions.

Automated Tumor Segmentation and Brain Tissue Extraction from Multiparametric MRI of Pediatric Brain Tumors: A Multi-Institutional Study.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related death among all childhood cancers. Tumor segmentation is essential in surgical and treatment planning, and response assessment and monitoring. However, manual segmentation is time-consuming and has high interoperator variability. We present a multi-institutional deep learning-based method for automated brain extraction and segmentation of pediatric brain tumors based on multi-parametric MRI scans. Methods: Multi-parametric scans (T1w, T1w-CE, T2, and T2-FLAIR) of 244 pediatric patients (n=215 internal and n=29 external cohorts) with de novo brain tumors, including a variety of tumor subtypes, were preprocessed and manually segmented to identify the brain tissue and tumor subregions into four tumor subregions, i.e., enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). The internal cohort was split into training (n=151), validation (n=43), and withheld internal test (n=21) subsets. DeepMedic, a three-dimensional convolutional neural network, was trained and the model parameters were tuned. Finally, the network was evaluated on the withheld internal and external test cohorts. Results: Dice similarity score (median±SD) was 0.91±0.10/0.88±0.16 for the whole tumor, 0.73±0.27/0.84±0.29 for ET, 0.79±19/0.74±0.27 for union of all non-enhancing components (i.e., NET, CC, ED), and 0.98±0.02 for brain tissue in both internal/external test sets. Conclusions: Our proposed automated brain extraction and tumor subregion segmentation models demonstrated accurate performance on segmentation of the brain tissue and whole tumor regions in pediatric brain tumors and can facilitate detection of abnormal regions for further clinical measurements. Key Points: We proposed automated tumor segmentation and brain extraction on pediatric MRI.The volumetric measurements using our models agree with ground truth segmentations. Importance of the Study: The current response assessment in pediatric brain tumors (PBTs) is currently based on bidirectional or 2D measurements, which underestimate the size of non-spherical and complex PBTs in children compared to volumetric or 3D methods. There is a need for development of automated methods to reduce manual burden and intra- and inter-rater variability to segment tumor subregions and assess volumetric changes. Most currently available automated segmentation tools are developed on adult brain tumors, and therefore, do not generalize well to PBTs that have different radiological appearances. To address this, we propose a deep learning (DL) auto-segmentation method that shows promising results in PBTs, collected from a publicly available large-scale imaging dataset (Children's Brain Tumor Network; CBTN) that comprises multi-parametric MRI scans of multiple PBT types acquired across multiple institutions on different scanners and protocols. As a complementary to tumor segmentation, we propose an automated DL model for brain tissue extraction.

Unsupervised machine learning using K-means identifies radiomic subgroups of pediatric low-grade gliomas that correlate with key molecular markers.

INTRODUCTION: Despite advancements in molecular and histopathologic characterization of pediatric low-grade gliomas (pLGGs), there remains significant phenotypic heterogeneity among tumors with similar categorizations. We hypothesized that an unsupervised machine learning approach based on radiomic features may reveal distinct pLGG imaging subtypes. METHODS: Multi-parametric MR images (T1 pre- and post-contrast, T2, and T2 FLAIR) from 157 patients with pLGGs were collected and 881 quantitative radiomic features were extracted from tumorous region. Clustering was performed using K-means after applying principal component analysis (PCA) for feature dimensionality reduction. Molecular and demographic data was obtained from the PedCBioportal and compared between imaging subtypes. RESULTS: K-means identified three distinct imaging-based subtypes. Subtypes differed in mutational frequencies of BRAF (p < 0.05) as well as the gene expression of BRAF (p<0.05). It was also found that age (p < 0.05), tumor location (p < 0.01), and tumor histology (p < 0.0001) differed significantly between the imaging subtypes. CONCLUSION: In this exploratory work, it was found that clustering of pLGGs based on radiomic features identifies distinct, imaging-based subtypes that correlate with important molecular markers and demographic details. This finding supports the notion that incorporation of radiomic data could augment our ability to better characterize pLGGs.

The University of Pennsylvania glioblastoma (UPenn-GBM) cohort: advanced MRI, clinical, genomics, & radiomics.

Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the "University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics" (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during routine clinical practice, at the University of Pennsylvania Health System, (b) accompanying clinical, demographic, and molecular information, (d) perfusion and diffusion derivative volumes, (e) computationally-derived and manually-revised expert annotations of tumor sub-regions, as well as (f) quantitative imaging (also known as radiomic) features corresponding to each of these regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments.

Quantification of tumor microenvironment acidity in glioblastoma using principal component analysis of dynamic susceptibility contrast enhanced MR imaging.

Glioblastoma (GBM) has high metabolic demands, which can lead to acidification of the tumor microenvironment. We hypothesize that a machine learning model built on temporal principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI can be used to estimate tumor acidity in GBM, as estimated by pH-sensitive amine chemical exchange saturation transfer echo-planar imaging (CEST-EPI). We analyzed 78 MRI scans in 32 treatment naïve and post-treatment GBM patients. All patients were imaged with DSC-MRI, and pH-weighting that was quantified from CEST-EPI estimation of the magnetization transfer ratio asymmetry (MTRasym) at 3 ppm. Enhancing tumor (ET), non-enhancing core (NC), and peritumoral T2 hyperintensity (namely, edema, ED) were used to extract principal components (PCs) and to build support vector machines regression (SVR) models to predict MTRasym values using PCs. Our predicted map correlated with MTRasym values with Spearman's r equal to 0.66, 0.47, 0.67, 0.71, in NC, ET, ED, and overall, respectively (p < 0.006). The results of this study demonstrates that PCA analysis of DSC imaging data can provide information about tumor pH in GBM patients, with the strongest association within the peritumoral regions.

Accuracy of diffusion-weighted imaging-magnetic resonance in differentiating functional from non-functional pituitary macro-adenoma and classification of tumor consistency.

PURPOSE: 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.

Heterogeneity analysis of diffusion-weighted MRI for prediction and assessment of microstructural changes early after one cycle of induction chemotherapy in nasopharyngeal cancer patients.

PURPOSE: To evaluate whether the pretreatment apparent diffusion coefficient (ADC) heterogeneity parameters and their alterations, after one cycle of induction chemotherapy, can be used as reliable markers of treatment response to induction chemotherapy in patients with nasopharyngeal cancer. MATERIALS AND METHODS: Ten patients were recruited and received induction chemotherapy (IC). Diffusion-weighted imaging was performed prior to, during, and after IC. The first-order ADC histogram parameters at the intra-treatment time-point were compared to the baseline time-point in the metastatic lymph nodes (LNs). Some ADC pretreatment parameters were combined with each other, employing discriminant analysis to achieve a feasible model to separate the complete response (CR) from the partial response (PR) groups. RESULTS: For ten patients, significant rise in Mean and Txt1Mean (p = 0.048 and 0.015, respectively) was observed in the metastatic nodes following one cycle of IC. Txt5Energy significantly decreased (p = 0.002). Discriminant analysis on pretreatment parameters illustrated that Txt5Energypre was the best parameter to use to correctly classify CR and PR patients. This was followed by Txt9Percentile75pre, Txt1Meanpre, and Txt2Standard Deviationpre. CONCLUSIONS: Our results suggest that heterogeneity metrics extracted from ADC-maps in metastatic lymph nodes, before and after IC, can be used as supplementary IC response indicators.

Semiquantitative dynamic contrast-enhanced MRI for accurate classification of complex adnexal masses.

PURPOSE: To identify the best dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) descriptive parameters in predicting malignancy of complex ovarian masses, and develop an optimal decision tree for accurate classification of benign and malignant complex ovarian masses. MATERIALS AND METHODS: Preoperative DCE-MR images of 55 sonographically indeterminate ovarian masses (27 benign and 28 malignant) were analyzed prospectively. Four descriptive parameters of the dynamic curve, namely, time-to-peak (TTP), wash-in-rate (WIR), relative signal intensity (SIrel ), and the initial area under the curve (IAUC60 ) were calculated on the normalized curves of specified regions-of-interest (ROIs). A two-tailed Student's t-test and two automated classifiers, linear discriminant analysis (LDA) and support vector machines (SVMs), were used to compare the performance of the mentioned parameters individually and in combination with each other. RESULTS: TTP (P = 6.15E-8) and WIR (P = 5.65E-5) parameters induced the highest sensitivity (89% for LDA, and 97% for SVM) and specificity (93% for LDA, and 100% for SVM), respectively. Regarding the high sensitivity of TTP and high specificity of WIR and through their combination, an accurate and simple decision-tree classifier was designed using the line equation obtained by LDA classification model. The proposed classifier achieved an accuracy of 89% and area under the ROC curve of 93%. CONCLUSION: In this study an accurate decision-tree classifier based on a combination of TTP and WIR parameters was proposed, which provides a clinically flexible framework to aid radiologists/clinicians to reach a conclusive preoperative diagnosis and patient-specific therapy plan for distinguishing malignant from benign complex ovarian masses. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:418-427.

A high throughput and efficient visualization method for diffusion tensor imaging of human brain white matter employing diffusion-map space.

Diffusion tensor imaging (DTI) possesses high dimension and complex structure, so that detecting available pattern information and its analysis based on conventional linear statistics and classification methods become inefficient. In order to facilitate classification, segmentation, compression or visualization of the data, dimension reduction is far-reaching. There have been many approaches proposed for this purpose, which mostly rely on complex low dimensional manifold embedding of the high-dimensional space. Dimension reduction is commonly applicable through linear algorithms, such as principal component analysis and multi-dimensional scaling; however, they are not able to deal with complex and high dimensional data. In this light, nonlinear algorithms with the capability to preserve the distance of high dimensional data have been developed. The purpose of this paper is to propose a new method for meaningful visualization of brain white matter using diffusion tensor data to map the 6-dimensional tensor to a three dimensional space employing Markov random walk and diffusion distance algorithms, leading to a new distance-preserving map for the DTI data with lower dimension and higher throughput information.