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Bennett A. Landman

Publications and source records attributed to Bennett A. Landman.

At least 127 records · Page 7Linked to original sources

CircleNet: Anchor-free Detection with Circle Representation

Object detection networks are powerful in computer vision, but not necessarily optimized for biomedical object detection. In this work, we propose CircleNet, a simple anchor-free detection method with circle representation for detection of the ball-shaped glomerulus. Different from the traditional bounding box based detection method, the bounding circle (1) reduces the degrees of freedom of detection representation, (2) is naturally rotation invariant, (3) and optimized for ball-shaped objects. The key innovation to enable this representation is the anchor-free framework with the circle detection head. We evaluate CircleNet in the context of detection of glomerulus. CircleNet increases average precision of the glomerulus detection from 0.598 to 0.647. Another key advantage is that CircleNet achieves better rotation consistency compared with bounding box representations.

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Enabling Multi-Shell b-Value Generalizability of Data-Driven Diffusion Models with Deep SHORE

Intra-voxel models of the diffusion signal are essential for interpreting organization of the tissue environment at micrometer level with data at millimeter resolution. Recent advances in data driven methods have enabled direct compari-son and optimization of methods for in-vivo data with externally validated histological sections with both 2-D and 3-D histology. Yet, all existing methods make limiting assumptions of either (1) model-based linkages between b-values or (2) limited associations with single shell data. We generalize prior deep learning models that used single shell spherical harmonic transforms to integrate the re-cently developed simple harmonic oscillator reconstruction (SHORE) basis. To enable learning on the SHORE manifold, we present an alternative formulation of the fiber orientation distribution (FOD) object using the SHORE basis while rep-resenting the observed diffusion weighted data in the SHORE basis. To ensure consistency of hyper-parameter optimization for SHORE, we present our Deep SHORE approach to learn on a data-optimized manifold. Deep SHORE is evalu-ated with eight-fold cross-validation of a preclinical MRI-histology data with four b-values. Generalizability of in-vivo human data is evaluated on two separate 3T MRI scanners. Specificity in terms of angular correlation (ACC) with the preclinical data improved on single shell: 0.78 relative to 0.73 and 0.73, multi-shell: 0.80 relative to 0.74 (p < 0.001). In the in-vivo human data, Deep SHORE was more consistent across scanners with 0.63 relative to other multi-shell methods 0.39, 0.52 and 0.57 in terms of ACC. In conclusion, Deep SHORE is a promising method to enable data driven learning with DW-MRI under conditions with varying b-values, number of diffusion shells, and gradient directions per shell.

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Deep Learning Estimation of Multi-Tissue Constrained Spherical Deconvolution with Limited Single Shell DW-MRI

Diffusion-weighted magnetic resonance imaging (DW-MRI) is the only non-invasive approach for estimation of intra-voxel tissue microarchitecture and reconstruction of in vivo neural pathways for the human brain. With improvement in accelerated MRI acquisition technologies, DW-MRI protocols that make use of multiple levels of diffusion sensitization have gained popularity. A well-known advanced method for reconstruction of white matter microstructure that uses multi-shell data is multi-tissue constrained spherical deconvolution (MT-CSD). MT-CSD substantially improves the resolution of intra-voxel structure over the traditional single shell version, constrained spherical deconvolution (CSD). Herein, we explore the possibility of using deep learning on single shell data (using the b=1000 s/mm2 from the Human Connectome Project (HCP)) to estimate the information content captured by 8th order MT-CSD using the full three shell data (b=1000, 2000, and 3000 s/mm2 from HCP). Briefly, we examine two network architectures: 1.) Sequential network of fully connected dense layers with a residual block in the middle (ResDNN), 2.) Patch based convolutional neural network with a residual block (ResCNN). For both networks an additional output block for estimation of voxel fraction was used with a modified loss function. Each approach was compared against the baseline of using MT-CSD on all data on 15 subjects from the HCP divided into 5 training, 2 validation, and 8 testing subjects with a total of 6.7 million voxels. The fiber orientation distribution function (fODF) can be recovered with high correlation (0.77 vs 0.74 and 0.65) as compared to the ground truth of MT-CST, which was derived from the multi-shell DW-MRI acquisitions. Source code and models have been made publicly available.

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Deep Multi-task Prediction of Lung Cancer and Cancer-free Progression from Censored Heterogenous Clinical Imaging

Annual low dose computed tomography (CT) lung screening is currently advised for individuals at high risk of lung cancer (e.g., heavy smokers between 55 and 80 years old). The recommended screening practice significantly reduces all-cause mortality, but the vast majority of screening results are negative for cancer. If patients at very low risk could be identified based on individualized, image-based biomarkers, the health care resources could be more efficiently allocated to higher risk patients and reduce overall exposure to ionizing radiation. In this work, we propose a multi-task (diagnosis and prognosis) deep convolutional neural network to improve the diagnostic accuracy over a baseline model while simultaneously estimating a personalized cancer-free progression time (CFPT). A novel Censored Regression Loss (CRL) is proposed to perform weakly supervised regression so that even single negative screening scans can provide small incremental value. Herein, we study 2287 scans from 1433 de-identified patients from the Vanderbilt Lung Screening Program (VLSP) and Molecular Characterization Laboratories (MCL) cohorts. Using five-fold cross-validation, we train a 3D attention-based network under two scenarios: (1) single-task learning with only classification, and (2) multi-task learning with both classification and regression. The single-task learning leads to a higher AUC compared with the Kaggle challenge winner pre-trained model (0.878 v. 0.856), and multi-task learning significantly improves the single-task one (AUC 0.895, p<0.01, McNemar test). In summary, the image-based predicted CFPT can be used in follow-up year lung cancer prediction and data assessment.

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Outlier Guided Optimization of Abdominal Segmentation

Abdominal multi-organ segmentation of computed tomography (CT) images has been the subject of extensive research interest. It presents a substantial challenge in medical image processing, as the shape and distribution of abdominal organs can vary greatly among the population and within an individual over time. While continuous integration of novel datasets into the training set provides potential for better segmentation performance, collection of data at scale is not only costly, but also impractical in some contexts. Moreover, it remains unclear what marginal value additional data have to offer. Herein, we propose a single-pass active learning method through human quality assurance (QA). We built on a pre-trained 3D U-Net model for abdominal multi-organ segmentation and augmented the dataset either with outlier data (e.g., exemplars for which the baseline algorithm failed) or inliers (e.g., exemplars for which the baseline algorithm worked). The new models were trained using the augmented datasets with 5-fold cross-validation (for outlier data) and withheld outlier samples (for inlier data). Manual labeling of outliers increased Dice scores with outliers by 0.130, compared to an increase of 0.067 with inliers (p<0.001, two-tailed paired t-test). By adding 5 to 37 inliers or outliers to training, we find that the marginal value of adding outliers is higher than that of adding inliers. In summary, improvement on single-organ performance was obtained without diminishing multi-organ performance or significantly increasing training time. Hence, identification and correction of baseline failure cases present an effective and efficient method of selecting training data to improve algorithm performance.

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Validation and Optimization of Multi-Organ Segmentation on Clinical Imaging Archives

Segmentation of abdominal computed tomography(CT) provides spatial context, morphological properties, and a framework for tissue-specific radiomics to guide quantitative Radiological assessment. A 2015 MICCAI challenge spurred substantial innovation in multi-organ abdominal CT segmentation with both traditional and deep learning methods. Recent innovations in deep methods have driven performance toward levels for which clinical translation is appealing. However, continued cross-validation on open datasets presents the risk of indirect knowledge contamination and could result in circular reasoning. Moreover, 'real world' segmentations can be challenging due to the wide variability of abdomen physiology within patients. Herein, we perform two data retrievals to capture clinically acquired deidentified abdominal CT cohorts with respect to a recently published variation on 3D U-Net (baseline algorithm). First, we retrieved 2004 deidentified studies on 476 patients with diagnosis codes involving spleen abnormalities (cohort A). Second, we retrieved 4313 deidentified studies on 1754 patients without diagnosis codes involving spleen abnormalities (cohort B). We perform prospective evaluation of the existing algorithm on both cohorts, yielding 13% and 8% failure rate, respectively. Then, we identified 51 subjects in cohort A with segmentation failures and manually corrected the liver and gallbladder labels. We re-trained the model adding the manual labels, resulting in performance improvement of 9% and 6% failure rate for the A and B cohorts, respectively. In summary, the performance of the baseline on the prospective cohorts was similar to that on previously published datasets. Moreover, adding data from the first cohort substantively improved performance when evaluated on the second withheld validation cohort.

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Internal-transfer Weighting of Multi-task Learning for Lung Cancer Detection

Recently, multi-task networks have shown to both offer additional estimation capabilities, and, perhaps more importantly, increased performance over single-task networks on a "main/primary" task. However, balancing the optimization criteria of multi-task networks across different tasks is an area of active exploration. Here, we extend a previously proposed 3D attention-based network with four additional multi-task subnetworks for the detection of lung cancer and four auxiliary tasks (diagnosis of asthma, chronic bronchitis, chronic obstructive pulmonary disease, and emphysema). We introduce and evaluate a learning policy, Periodic Focusing Learning Policy (PFLP), that alternates the dominance of tasks throughout the training. To improve performance on the primary task, we propose an Internal-Transfer Weighting (ITW) strategy to suppress the loss functions on auxiliary tasks for the final stages of training. To evaluate this approach, we examined 3386 patients (single scan per patient) from the National Lung Screening Trial (NLST) and de-identified data from the Vanderbilt Lung Screening Program, with a 2517/277/592 (scans) split for training, validation, and testing. Baseline networks include a single-task strategy and a multi-task strategy without adaptive weights (PFLP/ITW), while primary experiments are multi-task trials with either PFLP or ITW or both. On the test set for lung cancer prediction, the baseline single-task network achieved prediction AUC of 0.8080 and the multi-task baseline failed to converge (AUC 0.6720). However, applying PFLP helped multi-task network clarify and achieved test set lung cancer prediction AUC of 0.8402. Furthermore, our ITW technique boosted the PFLP enabled multi-task network and achieved an AUC of 0.8462 (McNemar test, p < 0.01).

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Methods and open-source toolkit for analyzing and visualizing challenge results

Biomedical challenges have become the de facto standard for benchmarking biomedical image analysis algorithms. While the number of challenges is steadily increasing, surprisingly little effort has been invested in ensuring high quality design, execution and reporting for these international competitions. Specifically, results analysis and visualization in the event of uncertainties have been given almost no attention in the literature. Given these shortcomings, the contribution of this paper is two-fold: (1) We present a set of methods to comprehensively analyze and visualize the results of single-task and multi-task challenges and apply them to a number of simulated and real-life challenges to demonstrate their specific strengths and weaknesses; (2) We release the open-source framework challengeR as part of this work to enable fast and wide adoption of the methodology proposed in this paper. Our approach offers an intuitive way to gain important insights into the relative and absolute performance of algorithms, which cannot be revealed by commonly applied visualization techniques. This is demonstrated by the experiments performed within this work. Our framework could thus become an important tool for analyzing and visualizing challenge results in the field of biomedical image analysis and beyond.

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Stochastic tissue window normalization of deep learning on computed tomography

Tissue window filtering has been widely used in deep learning for computed tomography (CT) image analyses to improve training performance (e.g., soft tissue windows for abdominal CT). However, the effectiveness of tissue window normalization is questionable since the generalizability of the trained model might be further harmed, especially when such models are applied to new cohorts with different CT reconstruction kernels, contrast mechanisms, dynamic variations in the acquisition, and physiological changes. We evaluate the effectiveness of both with and without using soft tissue window normalization on multisite CT cohorts. Moreover, we propose a stochastic tissue window normalization (SWN) method to improve the generalizability of tissue window normalization. Different from the random sampling, the SWN method centers the randomization around the soft tissue window to maintain the specificity for abdominal organs. To evaluate the performance of different strategies, 80 training and 453 validation and testing scans from six datasets are employed to perform multi-organ segmentation using standard 2D U-Net. The six datasets cover the scenarios, where the training and testing scans are from (1) same scanner and same population, (2) same CT contrast but different pathology, and (3) different CT contrast and pathology. The traditional soft tissue window and nonwindowed approaches achieved better performance on (1). The proposed SWN achieved general superior performance on (2) and (3) with statistical analyses, which offers better generalizability for a trained model.

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Contrast Phase Classification with a Generative Adversarial Network

Dynamic contrast enhanced computed tomography (CT) is an imaging technique that provides critical information on the relationship of vascular structure and dynamics in the context of underlying anatomy. A key challenge for image processing with contrast enhanced CT is that phase discrepancies are latent in different tissues due to contrast protocols, vascular dynamics, and metabolism variance. Previous studies with deep learning frameworks have been proposed for classifying contrast enhancement with networks inspired by computer vision. Here, we revisit the challenge in the context of whole abdomen contrast enhanced CTs. To capture and compensate for the complex contrast changes, we propose a novel discriminator in the form of a multi-domain disentangled representation learning network. The goal of this network is to learn an intermediate representation that separates contrast enhancement from anatomy and enables classification of images with varying contrast time. Briefly, our unpaired contrast disentangling GAN(CD-GAN) Discriminator follows the ResNet architecture to classify a CT scan from different enhancement phases. To evaluate the approach, we trained the enhancement phase classifier on 21060 slices from two clinical cohorts of 230 subjects. Testing was performed on 9100 slices from 30 independent subjects who had been imaged with CT scans from all contrast phases. Performance was quantified in terms of the multi-class normalized confusion matrix. The proposed network significantly improved correspondence over baseline UNet, ResNet50 and StarGAN performance of accuracy scores 0.54. 0.55, 0.62 and 0.91, respectively. The proposed discriminator from the disentangled network presents a promising technique that may allow deeper modeling of dynamic imaging against patient specific anatomies.

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Extracting 2D weak labels from volume labels using multiple instance learning in CT hemorrhage detection

Multiple instance learning (MIL) is a supervised learning methodology that aims to allow models to learn instance class labels from bag class labels, where a bag is defined to contain multiple instances. MIL is gaining traction for learning from weak labels but has not been widely applied to 3D medical imaging. MIL is well-suited to clinical CT acquisitions since (1) the highly anisotropic voxels hinder application of traditional 3D networks and (2) patch-based networks have limited ability to learn whole volume labels. In this work, we apply MIL with a deep convolutional neural network to identify whether clinical CT head image volumes possess one or more large hemorrhages (> 20cm$^3$), resulting in a learned 2D model without the need for 2D slice annotations. Individual image volumes are considered separate bags, and the slices in each volume are instances. Such a framework sets the stage for incorporating information obtained in clinical reports to help train a 2D segmentation approach. Within this context, we evaluate the data requirements to enable generalization of MIL by varying the amount of training data. Our results show that a training size of at least 400 patient image volumes was needed to achieve accurate per-slice hemorrhage detection. Over a five-fold cross-validation, the leading model, which made use of the maximum number of training volumes, had an average true positive rate of 98.10%, an average true negative rate of 99.36%, and an average precision of 0.9698. The models have been made available along with source code to enabled continued exploration and adaption of MIL in CT neuroimaging.

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Deep Learning Captures More Accurate Diffusion Fiber Orientations Distributions than Constrained Spherical Deconvolution

Confocal histology provides an opportunity to establish intra-voxel fiber orientation distributions that can be used to quantitatively assess the biological relevance of diffusion weighted MRI models, e.g., constrained spherical deconvolution (CSD). Here, we apply deep learning to investigate the potential of single shell diffusion weighted MRI to explain histologically observed fiber orientation distributions (FOD) and compare the derived deep learning model with a leading CSD approach. This study (1) demonstrates that there exists additional information in the diffusion signal that is not currently exploited by CSD, and (2) provides an illustrative data-driven model that makes use of this information.

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Semi-Supervised Multi-Organ Segmentation through Quality Assurance Supervision

Human in-the-loop quality assurance (QA) is typically performed after medical image segmentation to ensure that the systems are performing as intended, as well as identifying and excluding outliers. By performing QA on large-scale, previously unlabeled testing data, categorical QA scores can be generatedIn this paper, we propose a semi-supervised multi-organ segmentation deep neural network consisting of a traditional segmentation model generator and a QA involved discriminator. A large-scale dataset of 2027 volumes are used to train the generator, whose 2-D montage images and segmentation mask with QA scores are used to train the discriminator. To generate the QA scores, the 2-D montage images were reviewed manually and coded 0 (success), 1 (errors consistent with published performance), and 2 (gross failure). Then, the ResNet-18 network was trained with 1623 montage images in equal distribution of all three code labels and achieved an accuracy 94% for classification predictions with 404 montage images withheld for the test cohort. To assess the performance of using the QA supervision, the discriminator was used as a loss function in a multi-organ segmentation pipeline. The inclusion of QA-loss function boosted performance on the unlabeled test dataset from 714 patients to 951 patients over the baseline model. Additionally, the number of failures decreased from 606 (29.90%) to 402 (19.83%). The contributions of the proposed method are threefold: We show that (1) the QA scores can be used as a loss function to perform semi-supervised learning for unlabeled data, (2) the well trained discriminator is learnt by QA score rather than traditional true/false, and (3) the performance of multi-organ segmentation on unlabeled datasets can be fine-tuned with more robust and higher accuracy than the original baseline method.

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SynSeg-Net: Synthetic Segmentation Without Target Modality Ground Truth

A key limitation of deep convolutional neural networks (DCNN) based image segmentation methods is the lack of generalizability. Manually traced training images are typically required when segmenting organs in a new imaging modality or from distinct disease cohort. The manual efforts can be alleviated if the manually traced images in one imaging modality (e.g., MRI) are able to train a segmentation network for another imaging modality (e.g., CT). In this paper, we propose an end-to-end synthetic segmentation network (SynSeg-Net) to train a segmentation network for a target imaging modality without having manual labels. SynSeg-Net is trained by using (1) unpaired intensity images from source and target modalities, and (2) manual labels only from source modality. SynSeg-Net is enabled by the recent advances of cycle generative adversarial networks (CycleGAN) and DCNN. We evaluate the performance of the SynSeg-Net on two experiments: (1) MRI to CT splenomegaly synthetic segmentation for abdominal images, and (2) CT to MRI total intracranial volume synthetic segmentation (TICV) for brain images. The proposed end-to-end approach achieved superior performance to two stage methods. Moreover, the SynSeg-Net achieved comparable performance to the traditional segmentation network using target modality labels in certain scenarios. The source code of SynSeg-Net is publicly available (https://github.com/MASILab/SynSeg-Net).

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Why rankings of biomedical image analysis competitions should be interpreted with care

International challenges have become the standard for validation of biomedical image analysis methods. Given their scientific impact, it is surprising that a critical analysis of common practices related to the organization of challenges has not yet been performed. In this paper, we present a comprehensive analysis of biomedical image analysis challenges conducted up to now. We demonstrate the importance of challenges and show that the lack of quality control has critical consequences. First, reproducibility and interpretation of the results is often hampered as only a fraction of relevant information is typically provided. Second, the rank of an algorithm is generally not robust to a number of variables such as the test data used for validation, the ranking scheme applied and the observers that make the reference annotations. To overcome these problems, we recommend best practice guidelines and define open research questions to be addressed in the future.

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Distanced LSTM: Time-Distanced Gates in Long Short-Term Memory Models for Lung Cancer Detection

The field of lung nodule detection and cancer prediction has been rapidly developing with the support of large public data archives. Previous studies have largely focused on cross-sectional (single) CT data. Herein, we consider longitudinal data. The Long Short-Term Memory (LSTM) model addresses learning with regularly spaced time points (i.e., equal temporal intervals). However, clinical imaging follows patient needs with often heterogeneous, irregular acquisitions. To model both regular and irregular longitudinal samples, we generalize the LSTM model with the Distanced LSTM (DLSTM) for temporally varied acquisitions. The DLSTM includes a Temporal Emphasis Model (TEM) that enables learning across regularly and irregularly sampled intervals. Briefly, (1) the time intervals between longitudinal scans are modeled explicitly, (2) temporally adjustable forget and input gates are introduced for irregular temporal sampling; and (3) the latest longitudinal scan has an additional emphasis term. We evaluate the DLSTM framework in three datasets including simulated data, 1794 National Lung Screening Trial (NLST) scans, and 1420 clinically acquired data with heterogeneous and irregular temporal accession. The experiments on the first two datasets demonstrate that our method achieves competitive performance on both simulated and regularly sampled datasets (e.g. improve LSTM from 0.6785 to 0.7085 on F1 score in NLST). In external validation of clinically and irregularly acquired data, the benchmarks achieved 0.8350 (CNN feature) and 0.8380 (LSTM) on the area under the ROC curve (AUC) score, while the proposed DLSTM achieves 0.8905.

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Generalizing Deep Whole Brain Segmentation for Pediatric and Post-Contrast MRI with Augmented Transfer Learning

Generalizability is an important problem in deep neural networks, especially in the context of the variability of data acquisition in clinical magnetic resonance imaging (MRI). Recently, the Spatially Localized Atlas Network Tiles (SLANT) approach has been shown to effectively segment whole brain non-contrast T1w MRI with 132 volumetric labels. Enhancing generalizability of SLANT would enable broader application of volumetric assessment in multi-site studies. Transfer learning (TL) is commonly used to update the neural network weights for local factors; yet, it is commonly recognized to risk degradation of performance on the original validation/test cohorts. Here, we explore TL by data augmentation to address these concerns in the context of adapting SLANT to anatomical variation and scanning protocol. We consider two datasets: First, we optimize for age with 30 T1w MRI of young children with manually corrected volumetric labels, and accuracy of automated segmentation defined relative to the manually provided truth. Second, we optimize for acquisition with 36 paired datasets of pre- and post-contrast clinically acquired T1w MRI, and accuracy of the post-contrast segmentations assessed relative to the pre-contrast automated assessment. For both studies, we augment the original TL step of SLANT with either only the new data or with both original and new data. Over baseline SLANT, both approaches yielded significantly improved performance (signed rank tests; pediatric: 0.89 vs. 0.82 DSC, p<0.001; contrast: 0.80 vs 0.76, p<0.001). The performance on the original test set decreased with the new-data only transfer learning approach, so data augmentation was superior to strict transfer learning.

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Cortical Surface Parcellation using Spherical Convolutional Neural Networks

We present cortical surface parcellation using spherical deep convolutional neural networks. Traditional multi-atlas cortical surface parcellation requires inter-subject surface registration using geometric features with high processing time on a single subject (2-3 hours). Moreover, even optimal surface registration does not necessarily produce optimal cortical parcellation as parcel boundaries are not fully matched to the geometric features. In this context, a choice of training features is important for accurate cortical parcellation. To utilize the networks efficiently, we propose cortical parcellation-specific input data from an irregular and complicated structure of cortical surfaces. To this end, we align ground-truth cortical parcel boundaries and use their resulting deformation fields to generate new pairs of deformed geometric features and parcellation maps. To extend the capability of the networks, we then smoothly morph cortical geometric features and parcellation maps using the intermediate deformation fields. We validate our method on 427 adult brains for 49 labels. The experimental results show that our method out-performs traditional multi-atlas and naive spherical U-Net approaches, while achieving full cortical parcellation in less than a minute.

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