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  • 1
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-12-05)
    Abstract: Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature ( n  = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    In: Applied Sciences, MDPI AG, Vol. 11, No. 4 ( 2021-02-21), p. 1892-
    Abstract: Histopathologic assessment routinely provides rich microscopic information about tissue structure and disease process. However, the sections used are very thin, and essentially capture only 2D representations of a certain tissue sample. Accurate and robust alignment of sequentially cut 2D slices should contribute to more comprehensive assessment accounting for surrounding 3D information. Towards this end, we here propose a two-step diffeomorphic registration approach that aligns differently stained histology slides to each other, starting with an initial affine step followed by estimating a deformation field. It was quantitatively evaluated on ample (n = 481) and diverse data from the automatic non-rigid histological image registration challenge, where it was awarded the second rank. The obtained results demonstrate the ability of the proposed approach to robustly (average robustness = 0.9898) and accurately (average relative target registration error = 0.2%) align differently stained histology slices of various anatomical sites while maintaining reasonable computational efficiency ( 〈 1 min per registration). The method was developed by adapting a general-purpose registration algorithm designed for 3D radiographic scans and achieved consistently accurate results for aligning high-resolution 2D histologic images. Accurate alignment of histologic images can contribute to a better understanding of the spatial arrangement and growth patterns of cells, vessels, matrix, nerves, and immune cell interactions.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 3
    In: Applied Sciences, MDPI AG, Vol. 11, No. 16 ( 2021-08-15), p. 7488-
    Abstract: We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% on average. We found significant (p 〈 0.001) overlap difference for spleen (DiceIML/DiceManual = 0.91/0.87), breast tumors (DiceIML/DiceManual = 0.84/0.82), and lung nodules (DiceIML/DiceManual = 0.78/0.83). For intra-rater consistency, a significant (p = 0.003) difference was found for spleen (DiceIML/DiceManual = 0.91/0.89). For inter-rater consistency, significant (p 〈 0.045) differences were found for spleen (DiceIML/DiceManual = 0.91/0.87), breast (DiceIML/DiceManual = 0.86/0.81), lung (DiceIML/DiceManual = 0.85/0.89), the non-enhancing (DiceIML/DiceManual = 0.79/0.67) and the enhancing (DiceIML/DiceManual = 0.79/0.84) brain tumor sub-regions, which, in aggregation, favored our method. Quantitative evaluation for speed, spatial overlap, and consistency, reveals the benefits of our proposed method when compared with manual annotation, for several clinically relevant problems. We publicly release our implementation through CaPTk (Cancer Imaging Phenomics Toolkit) and as an MITK plugin.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 4
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 2, No. Supplement_4 ( 2020-12-31), p. iv22-iv34
    Abstract: Gliomas represent a biologically heterogeneous group of primary brain tumors with uncontrolled cellular proliferation and diffuse infiltration that renders them almost incurable, thereby leading to a grim prognosis. Recent comprehensive genomic profiling has greatly elucidated the molecular hallmarks of gliomas, including the mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), loss of chromosomes 1p and 19q (1p/19q), and epidermal growth factor receptor variant III (EGFRvIII). Detection of these molecular alterations is based on ex vivo analysis of surgically resected tissue specimen that sometimes is not adequate for testing and/or does not capture the spatial tumor heterogeneity of the neoplasm. Methods We developed a method for noninvasive detection of radiogenomic markers of IDH both in lower-grade gliomas (WHO grade II and III tumors) and glioblastoma (WHO grade IV), 1p/19q in IDH-mutant lower-grade gliomas, and EGFRvIII in glioblastoma. Preoperative MRIs of 473 glioma patients from 3 of the studies participating in the ReSPOND consortium (collection I: Hospital of the University of Pennsylvania [HUP: n = 248], collection II: The Cancer Imaging Archive [TCIA; n = 192] , and collection III: Ohio Brain Tumor Study [OBTS, n = 33]) were collected. Neuro-Cancer Imaging Phenomics Toolkit (neuro-CaPTk), a modular platform available for cancer imaging analytics and machine learning, was leveraged to extract histogram, shape, anatomical, and texture features from delineated tumor subregions and to integrate these features using support vector machine to generate models predictive of IDH, 1p/19q, and EGFRvIII. The models were validated using 3 configurations: (1) 70–30% training–testing splits or 10-fold cross-validation within individual collections, (2) 70–30% training–testing splits within merged collections, and (3) training on one collection and testing on another. Results These models achieved a classification accuracy of 86.74% (HUP), 85.45% (TCIA), and 75.15% (TCIA) in identifying EGFRvIII, IDH, and 1p/19q, respectively, in configuration I. The model, when applied on combined data in configuration II, yielded a classification success rate of 82.50% in predicting IDH mutation (HUP + TCIA + OBTS). The model when trained on TCIA dataset yielded classification accuracy of 84.88% in predicting IDH in HUP dataset. Conclusions Using machine learning algorithms, high accuracy was achieved in the prediction of IDH, 1p/19q, and EGFRvIII mutation. Neuro-CaPTk encompasses all the pipelines required to replicate these analyses in multi-institutional settings and could also be used for other radio(geno)mic analyses.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii229-ii229
    Abstract: Glioblastomas are arguably the most aggressive, infiltrative, and heterogeneous adult brain tumor. Biophysical modeling of glioblastoma growth has shown its predictive value towards clinical endpoints, enabling more informed decision-making. However, the mathematically rigorous formulations of biophysical modeling come with a large computational footprint, hindering their application to clinical studies. METHODS We present a deep learning (DL)-based logistical regression model, to estimate in seconds glioblastoma biophysical growth, defined through three tumor-specific parameters: 1) diffusion coefficient of white matter (Dw), which describes how easily the tumor can infiltrate through the white matter, 2) mass-effect parameter (Mp), which defines the average tumor expansion, and 3) estimated time (T) in number of days that the tumor has been growing. Pre-operative multi-parametric MRI (mpMRI) structural scans (T1, T1-Gd, T1, T2-FLAIR) from 135 subjects of the TCGA-GBM imaging collection are used to quantitatively evaluate our approach. We consider the mpMRI intensities within the region defined by the abnormal T2-FLAIR signal envelope, for training three DL models for the three tumor-specific parameters. Each of our DL models consist of two sets of convolution layers followed by a single max-pooling layer, with a normalized root mean squared error as the minimization metric and evaluated using 10-fold cross validation. We train and validate the DL-based predictions against parameters derived from biophysical inversion models. RESULTS Pearson correlation coefficients between our DL-based estimations and the biophysical parameters were equal to 0.85 for Dw, 0.90 for Mp, and 0.94 for T. CONCLUSION This study unlocks the power of tumor-specific parameters from biophysical tumor growth estimation, paving the way towards their utilization in more clinical studies, while opening the door for leveraging advanced radiomic descriptors in future studies, as well as allowing for significantly faster parameter reconstruction compared to biophysical growth modeling approaches. *denotes equal senior authorship.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 6
    In: Scientific Data, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2022-07-29)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2052-4463
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 7
    In: Medical Physics, Wiley, Vol. 47, No. 12 ( 2020-12), p. 6039-6052
    Abstract: The availability of radiographic magnetic resonance imaging (MRI) scans for the Ivy Glioblastoma Atlas Project (Ivy GAP) has opened up opportunities for development of radiomic markers for prognostic/predictive applications in glioblastoma (GBM). In this work, we address two critical challenges with regard to developing robust radiomic approaches: (a) the lack of availability of reliable segmentation labels for glioblastoma tumor sub‐compartments (i.e., enhancing tumor, non‐enhancing tumor core, peritumoral edematous/infiltrated tissue) and (b) identifying “reproducible” radiomic features that are robust to segmentation variability across readers/sites. Acquisition and validation methods From TCIA’s Ivy GAP cohort, we obtained a paired set (n = 31) of expert annotations approved by two board‐certified neuroradiologists at the Hospital of the University of Pennsylvania (UPenn) and at Case Western Reserve University (CWRU). For these studies, we performed a reproducibility study that assessed the variability in (a) segmentation labels and (b) radiomic features, between these paired annotations. The radiomic variability was assessed on a comprehensive panel of 11 700 radiomic features including intensity, volumetric, morphologic, histogram‐based, and textural parameters, extracted for each of the paired sets of annotations. Our results demonstrated (a) a high level of inter‐rater agreement (median value of DICE ≥0.8 for all sub‐compartments), and (b) ≈24% of the extracted radiomic features being highly correlated (based on Spearman’s rank correlation coefficient) to annotation variations. These robust features largely belonged to morphology (describing shape characteristics), intensity (capturing intensity profile statistics), and COLLAGE (capturing heterogeneity in gradient orientations) feature families. Data format and usage notes We make publicly available on TCIA’s Analysis Results Directory (https://doi.org/10.7937/9j41‐7d44), the complete set of (a) multi‐institutional expert annotations for the tumor sub‐compartments, (b) 11 700 radiomic features, and (c) the associated reproducibility meta‐analysis. Potential applications The annotations and the associated meta‐data for Ivy GAP are released with the purpose of enabling researchers toward developing image‐based biomarkers for prognostic/predictive applications in GBM.
    Type of Medium: Online Resource
    ISSN: 0094-2405 , 2473-4209
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e13538-e13538
    Abstract: e13538 Background: Breast density is considered a well-established breast cancer risk factor. As quasi-3D, digital breast tomosynthesis (DBT) becomes increasingly utilized for screening, there is an opportunity to routinely estimate volumetric breast density (VBD). However, current methods extrapolate VBD from 2D images acquired with DBT and/or depend on the existence of raw DBT data, which is rarely archived due to cost and storage constraints. Using a racially diverse screening cohort, this study evaluates the potential of deep learning for VBD assessment based solely on 3D reconstructed, “for presentation” DBT images. Methods: We retrospectively analyzed 1,080 negative DBT screening exams obtained between 2011 and 2016 from the Hospital of the University of Pennsylvania (racial makeup, 41.2% White, 54.2% Black, 4.6% Other; mean age ± SD, 57 ± 11 years; mean BMI ± SD, 28.7 ± 7.1 kg/m2), for which both 2D raw and 3D reconstructed DBT images (Selenia Dimensions, Hologic Inc) were available. Corresponding 3D reference-standard tissue segmentations were generated from previously validated software that uses both 3D reconstructed slices and raw 2D DBT data to provide VBD metrics, shown to be strongly correlated with VBD measures from MRI image volumes. We based our deep learning algorithm on the U-Net architecture within the open-source Generally Nuanced Deep Learning Framework (GaNDLF) and created a 3-label image segmentation task (background, dense tissue, and fatty tissue). Our dataset was randomly split into training (70%), validation (15%) and test (15%) sets. We report on the performance of our deep learning algorithm against corresponding reference-standard segmentations for a cranio-caudal (CC) view-only subset. We also stratify our results by the two main racial groups (White and Black). Our evaluation measure was the weighted Dice score (DSC), with 0 signifying no overlap and 1 signifying perfect overlap, overall and separately for each label. Results: Our deep learning algorithm achieved an overall DSC of 0.682 (STD = 0.136). It accurately segmented the three labels of background, fatty tissue, and dense tissue, with DSC scores of 0.995, 0.884, and 0.617, respectively. DSC for White and Black women were 0.688 (STD = 0.127) and 0.680 (STD = 0.146), respectively. Conclusions: Our preliminary analysis suggests that deep learning shows promise in the estimation of VBD using 3D DBT reconstructed, “for presentation” CC view images and does not demonstrate bias among racial groups. Future work involving optimization of performance in other breast views as well as transfer learning based on ground truth masks by clinical radiologists could further enhance this method. In view of rapid clinical conversion to DBT screening, such a tool has the potential to enable large retrospective epidemiological and personalized risk assessment studies of breast density with DBT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
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    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 1929-1929
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 1929-1929
    Abstract: Background: It has been widely established that breast density is an independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from 2D images acquired with DBT and/or depend on the existence of raw DBT data which is rarely archived by clinical centers due to cost and storage constraints. This study aims to harness deep learning to develop a computational tool for VBD assessment based solely on 3D reconstructed, “for presentation” DBT images. Methods: We retrospectively analyzed 1,080 negative DBT screening exams (09/20/2011 - 11/25/2016) from the Hospital of the University of Pennsylvania (mean age ± SD, 57 ± 11 years; mean BMI ± SD, 28.7 ± 7.1 kg/m2; racial makeup, 41.2% White, 54.2% Black, 4.6% Other), for which both 3D reconstructed and 2D raw DBT images (Selenia Dimensions, Hologic Inc) were available. All available standard views (left and right mediolateral-oblique and cranio-caudal views) were included for each exam, leading to 7,850 DBT views. Corresponding 3D reference-standard tissue segmentations were generated from a previously validated software that uses both 3D reconstructed slices and raw 2D DBT data to provide VBD metrics, shown to be strongly correlated with VBD measures from MRI image volumes. We based our deep learning algorithm on the U-Net architecture within the open-source Generally Nuanced Deep Learning Framework (GaNDLF) and created a 3-label image segmentation task (background, dense tissue, and fatty tissue). Our dataset was randomly split into training (70%), validation (15%) and test (15%) sets, while ensuring that all views of the same DBT exam were assigned to the same set. The performance of our deep learning algorithm against the corresponding reference-standard segmentations was measured in terms of Dice scores (DSC), with 0 signifying no overlap and 1 signifying perfect overlap, overall, as well as separately for each label. Results: After training was complete, our deep learning algorithm achieved a DSC of 0.78 on the validation, as well as on the test set. Our method accurately segmented background from breast tissue (DSC = 0.94) and demonstrated moderate to high performance in segmenting dense and fatty tissue, respectively (DSC = 0.49 and 0.89). Conclusion: Our preliminary analysis suggests that deep learning shows promise in the estimation of VBD using 3D DBT reconstructed, “for presentation” images. Future work involving transfer learning based on ground truth masks by clinical radiologists could further enhance this method’s performance. In view of rapid clinical conversion to DBT screening, such a tool has the potential to enable large retrospective epidemiologic and personalized risk assessment studies of breast density with DBT. Citation Format: Vinayak S. Ahluwalia, Walter Mankowski, Sarthak Pati, Spyridon Bakas, Ari Brooks, Celine M. Vachon, Emily F. Conant, Aimilia Gastounioti, Despina Kontos. Deep-learning-enabled volumetric breast density estimation with digital breast tomosynthesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1929.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 10
    In: Communications Engineering, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2023-05-16)
    Abstract: Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k -fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.
    Type of Medium: Online Resource
    ISSN: 2731-3395
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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