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We propose a deep mixture of multimodal hierarchical variational auto-encoders called MMHVAE that synthesizes missing images from observed images in different modalities. MMHVAE's design focuses on tackling four challenges: (i) creating a complex latent representation of multimodal data to generate high-resolution images; (ii) encouraging the variational distributions to estimate the missing information needed for cross-modal image synthesis; (iii) learning to fuse multimodal information in the context of missing data; (iv) leveraging dataset-level information to handle incomplete data sets at training time. Extensive experiments are performed on the challenging problem of pre-operative brain multi-parametric magnetic resonance and intra-operative ultrasound imaging., Comment: Manuscript under review

We present a novel approach to calibrating linguistic expressions of certainty, e.g., "Maybe" and "Likely". Unlike prior work that assigns a single score to each certainty phrase, we model uncertainty as distributions over the simplex to capture their semantics more accurately. To accommodate this new representation of certainty, we generalize existing measures of miscalibration and introduce a novel post-hoc calibration method. Leveraging these tools, we analyze the calibration of both humans (e.g., radiologists) and computational models (e.g., language models) and provide interpretable suggestions to improve their calibration.

We propose in this paper a texture-invariant 2D keypoints descriptor specifically designed for matching preoperative Magnetic Resonance (MR) images with intraoperative Ultrasound (US) images. We introduce a matching-by-synthesis strategy, where intraoperative US images are synthesized from MR images accounting for multiple MR modalities and intraoperative US variability. We build our training set by enforcing keypoints localization over all images then train a patient-specific descriptor network that learns texture-invariant discriminant features in a supervised contrastive manner, leading to robust keypoints descriptors. Our experiments on real cases with ground truth show the effectiveness of the proposed approach, outperforming the state-of-the-art methods and achieving 80.35% matching precision on average., Comment: Accepted for publication at the International Workshop of Advances in Simplifying Medical UltraSound (ASMUS) at MICCAI 2024

Accurate assessment of lymph node size in 3D CT scans is crucial for cancer staging, therapeutic management, and monitoring treatment response. Existing state-of-the-art segmentation frameworks in medical imaging often rely on fully annotated datasets. However, for lymph node segmentation, these datasets are typically small due to the extensive time and expertise required to annotate the numerous lymph nodes in 3D CT scans. Weakly-supervised learning, which leverages incomplete or noisy annotations, has recently gained interest in the medical imaging community as a potential solution. Despite the variety of weakly-supervised techniques proposed, most have been validated only on private datasets or small publicly available datasets. To address this limitation, the Mediastinal Lymph Node Quantification (LNQ) challenge was organized in conjunction with the 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023). This challenge aimed to advance weakly-supervised segmentation methods by providing a new, partially annotated dataset and a robust evaluation framework. A total of 16 teams from 5 countries submitted predictions to the validation leaderboard, and 6 teams from 3 countries participated in the evaluation phase. The results highlighted both the potential and the current limitations of weakly-supervised approaches. On one hand, weakly-supervised approaches obtained relatively good performance with a median Dice score of $61.0\%$. On the other hand, top-ranked teams, with a median Dice score exceeding $70\%$, boosted their performance by leveraging smaller but fully annotated datasets to combine weak supervision and full supervision. This highlights both the promise of weakly-supervised methods and the ongoing need for high-quality, fully annotated data to achieve higher segmentation performance., Comment: Submitted to MELBA; Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2025:001

Intraoperative ultrasound (iUS) imaging has the potential to improve surgical outcomes in brain surgery. However, its interpretation is challenging, even for expert neurosurgeons. In this work, we designed the first patient-specific framework that performs brain tumor segmentation in trackerless iUS. To disambiguate ultrasound imaging and adapt to the neurosurgeon's surgical objective, a patient-specific real-time network is trained using synthetic ultrasound data generated by simulating virtual iUS sweep acquisitions in pre-operative MR data. Extensive experiments performed in real ultrasound data demonstrate the effectiveness of the proposed approach, allowing for adapting to the surgeon's definition of surgical targets and outperforming non-patient-specific models, neurosurgeon experts, and high-end tracking systems. Our code is available at: \url{https://github.com/ReubenDo/MHVAE-Seg}., Comment: Early accept at MICCAI 2024 - code available at: https://github.com/ReubenDo/MHVAE-Seg

With the wealth of medical image data, efficient curation is essential. Assigning the sequence type to magnetic resonance images is necessary for scientific studies and artificial intelligence-based analysis. However, incomplete or missing metadata prevents effective automation. We therefore propose a deep-learning method for classification of prostate cancer scanning sequences based on a combination of image data and DICOM metadata. We demonstrate superior results compared to metadata or image data alone, and make our code publicly available at https://github.com/deepakri201/DICOMScanClassification.

Accurate and scalable annotation of medical data is critical for the development of medical AI, but obtaining time for annotation from medical experts is challenging. Gamified crowdsourcing has demonstrated potential for obtaining highly accurate annotations for medical data at scale, and we demonstrate the same in this study for the segmentation of B-lines, an indicator of pulmonary congestion, on still frames within point-of-care lung ultrasound clips. We collected 21,154 annotations from 214 annotators over 2.5 days, and we demonstrated that the concordance of crowd consensus segmentations with reference standards exceeds that of individual experts with the same reference standards, both in terms of B-line count (mean squared error 0.239 vs. 0.308, p<0.05) as well as the spatial precision of B-line annotations (mean Dice-H score 0.755 vs. 0.643, p<0.05). These results suggest that expert-quality segmentations can be achieved using gamified crowdsourcing.

We present a novel method for intraoperative patient-to-image registration by learning Expected Appearances. Our method uses preoperative imaging to synthesize patient-specific expected views through a surgical microscope for a predicted range of transformations. Our method estimates the camera pose by minimizing the dissimilarity between the intraoperative 2D view through the optical microscope and the synthesized expected texture. In contrast to conventional methods, our approach transfers the processing tasks to the preoperative stage, reducing thereby the impact of low-resolution, distorted, and noisy intraoperative images, that often degrade the registration accuracy. We applied our method in the context of neuronavigation during brain surgery. We evaluated our approach on synthetic data and on retrospective data from 6 clinical cases. Our method outperformed state-of-the-art methods and achieved accuracies that met current clinical standards., Comment: Accepted at MICCAI 2023

We introduce MHVAE, a deep hierarchical variational auto-encoder (VAE) that synthesizes missing images from various modalities. Extending multi-modal VAEs with a hierarchical latent structure, we introduce a probabilistic formulation for fusing multi-modal images in a common latent representation while having the flexibility to handle incomplete image sets as input. Moreover, adversarial learning is employed to generate sharper images. Extensive experiments are performed on the challenging problem of joint intra-operative ultrasound (iUS) and Magnetic Resonance (MR) synthesis. Our model outperformed multi-modal VAEs, conditional GANs, and the current state-of-the-art unified method (ResViT) for synthesizing missing images, demonstrating the advantage of using a hierarchical latent representation and a principled probabilistic fusion operation. Our code is publicly available \url{https://github.com/ReubenDo/MHVAE}., Comment: Accepted at MICCAI 2023

Study Objective: Machine learning models have advanced medical image processing and can yield faster, more accurate diagnoses. Despite a wealth of available medical imaging data, high-quality labeled data for model training is lacking. We investigated whether a gamified crowdsourcing platform enhanced with inbuilt quality control metrics can produce lung ultrasound clip labels comparable to those from clinical experts. Methods: 2,384 lung ultrasound clips were retrospectively collected from 203 patients. Six lung ultrasound experts classified 393 of these clips as having no B-lines, one or more discrete B-lines, or confluent B-lines to create two sets of reference standard labels (195 training set clips and 198 test set clips). Sets were respectively used to A) train users on a gamified crowdsourcing platform, and B) compare concordance of the resulting crowd labels to the concordance of individual experts to reference standards. Results: 99,238 crowdsourced opinions on 2,384 lung ultrasound clips were collected from 426 unique users over 8 days. On the 198 test set clips, mean labeling concordance of individual experts relative to the reference standard was 85.0% +/- 2.0 (SEM), compared to 87.9% crowdsourced label concordance (p=0.15). When individual experts' opinions were compared to reference standard labels created by majority vote excluding their own opinion, crowd concordance was higher than the mean concordance of individual experts to reference standards (87.4% vs. 80.8% +/- 1.6; p<0.001). Conclusion: Crowdsourced labels for B-line classification via a gamified approach achieved expert-level quality. Scalable, high-quality labeling approaches may facilitate training dataset creation for machine learning model development., Comment: 27 pages total

Lung ultrasound (LUS) is an important imaging modality used by emergency physicians to assess pulmonary congestion at the patient bedside. B-line artifacts in LUS videos are key findings associated with pulmonary congestion. Not only can the interpretation of LUS be challenging for novice operators, but visual quantification of B-lines remains subject to observer variability. In this work, we investigate the strengths and weaknesses of multiple deep learning approaches for automated B-line detection and localization in LUS videos. We curate and publish, BEDLUS, a new ultrasound dataset comprising 1,419 videos from 113 patients with a total of 15,755 expert-annotated B-lines. Based on this dataset, we present a benchmark of established deep learning methods applied to the task of B-line detection. To pave the way for interpretable quantification of B-lines, we propose a novel "single-point" approach to B-line localization using only the point of origin. Our results show that (a) the area under the receiver operating characteristic curve ranges from 0.864 to 0.955 for the benchmarked detection methods, (b) within this range, the best performance is achieved by models that leverage multiple successive frames as input, and (c) the proposed single-point approach for B-line localization reaches an F1-score of 0.65, performing on par with the inter-observer agreement. The dataset and developed methods can facilitate further biomedical research on automated interpretation of lung ultrasound with the potential to expand the clinical utility., Comment: 10 pages, 4 figures

Ensembling is now recognized as an effective approach for increasing the predictive performance and calibration of deep networks. We introduce a new approach, Parameter Ensembling by Perturbation (PEP), that constructs an ensemble of parameter values as random perturbations of the optimal parameter set from training by a Gaussian with a single variance parameter. The variance is chosen to maximize the log-likelihood of the ensemble average ($\mathbb{L}$) on the validation data set. Empirically, and perhaps surprisingly, $\mathbb{L}$ has a well-defined maximum as the variance grows from zero (which corresponds to the baseline model). Conveniently, calibration level of predictions also tends to grow favorably until the peak of $\mathbb{L}$ is reached. In most experiments, PEP provides a small improvement in performance, and, in some cases, a substantial improvement in empirical calibration. We show that this "PEP effect" (the gain in log-likelihood) is related to the mean curvature of the likelihood function and the empirical Fisher information. Experiments on ImageNet pre-trained networks including ResNet, DenseNet, and Inception showed improved calibration and likelihood. We further observed a mild improvement in classification accuracy on these networks. Experiments on classification benchmarks such as MNIST and CIFAR-10 showed improved calibration and likelihood, as well as the relationship between the PEP effect and overfitting; this demonstrates that PEP can be used to probe the level of overfitting that occurred during training. In general, no special training procedure or network architecture is needed, and in the case of pre-trained networks, no additional training is needed., Comment: NeurIPS 2020

Fully convolutional neural networks (FCNs), and in particular U-Nets, have achieved state-of-the-art results in semantic segmentation for numerous medical imaging applications. Moreover, batch normalization and Dice loss have been used successfully to stabilize and accelerate training. However, these networks are poorly calibrated i.e. they tend to produce overconfident predictions both in correct and erroneous classifications, making them unreliable and hard to interpret. In this paper, we study predictive uncertainty estimation in FCNs for medical image segmentation. We make the following contributions: 1) We systematically compare cross entropy loss with Dice loss in terms of segmentation quality and uncertainty estimation of FCNs; 2) We propose model ensembling for confidence calibration of the FCNs trained with batch normalization and Dice loss; 3) We assess the ability of calibrated FCNs to predict segmentation quality of structures and detect out-of-distribution test examples. We conduct extensive experiments across three medical image segmentation applications of the brain, the heart, and the prostate to evaluate our contributions. The results of this study offer considerable insight into the predictive uncertainty estimation and out-of-distribution detection in medical image segmentation and provide practical recipes for confidence calibration. Moreover, we consistently demonstrate that model ensembling improves confidence calibration., Comment: Journal of IEEE Transactions on Medical Imaging

This paper establishes an information theoretic framework for deep metric based image registration techniques. We show an exact equivalence between maximum profile likelihood and minimization of joint entropy, an important early information theoretic registration method. We further derive deep classifier-based metrics that can be used with iterated maximum likelihood to achieve Deep Information Theoretic Registration on patches rather than pixels. This alleviates a major shortcoming of previous information theoretic registration approaches, namely the implicit pixel-wise independence assumptions. Our proposed approach does not require well-registered training data; this brings previous fully supervised deep metric registration approaches to the realm of weak supervision. We evaluate our approach on several image registration tasks and show significantly better performance compared to mutual information, specifically when images have substantially different contrasts. This work enables general-purpose registration in applications where current methods are not successful.

Deep metrics have been shown effective as similarity measures in multi-modal image registration; however, the metrics are currently constructed from aligned image pairs in the training data. In this paper, we propose a strategy for learning such metrics from roughly aligned training data. Symmetrizing the data corrects bias in the metric that results from misalignment in the data (at the expense of increased variance), while random perturbations to the data, i.e. dithering, ensures that the metric has a single mode, and is amenable to registration by optimization. Evaluation is performed on the task of registration on separate unseen test image pairs. The results demonstrate the feasibility of learning a useful deep metric from substantially misaligned training data, in some cases the results are significantly better than from Mutual Information. Data augmentation via dithering is, therefore, an effective strategy for discharging the need for well-aligned training data; this brings deep metric registration from the realm of supervised to semi-supervised machine learning., Comment: Under Review for MICCAI 2018

Accurate and reliable segmentation of catheters in MR-guided interventions remains a challenge, and a step of critical importance in clinical workflows. In this work, under reasonable assumptions, mechanical model based heuristics guide the segmentation process allows correct catheter identification rates greater than 98% (error 2.88 mm), and reduction in outliers to one-fourth compared to the state of the art. Given distal tips, searching towards the proximal ends of the catheters is guided by mechanical models that are estimated on a per-catheter basis. Their bending characteristics are used to constrain the image feature based candidate points. The final catheter trajectories are hybrid sequences of individual points, each derived from model and image features. We evaluate the method on a database of 10 patient MRI scans including 101 manually segmented catheters. The mean errors were 1.40 mm and the median errors were 1.05 mm. The number of outliers deviating more than 2 mm from the gold standard is 7, and the number of outliers deviating more than 3 mm from the gold standard is just 2., Comment: MICCAI 2015

Magnetic Resonance Imaging (MRI) is widely used in routine clinical diagnosis and treatment. However, variations in MRI acquisition protocols result in different appearances of normal and diseased tissue in the images. Convolutional neural networks (CNNs), which have shown to be successful in many medical image analysis tasks, are typically sensitive to the variations in imaging protocols. Therefore, in many cases, networks trained on data acquired with one MRI protocol, do not perform satisfactorily on data acquired with different protocols. This limits the use of models trained with large annotated legacy datasets on a new dataset with a different domain which is often a recurring situation in clinical settings. In this study, we aim to answer the following central questions regarding domain adaptation in medical image analysis: Given a fitted legacy model, 1) How much data from the new domain is required for a decent adaptation of the original network?; and, 2) What portion of the pre-trained model parameters should be retrained given a certain number of the new domain training samples? To address these questions, we conducted extensive experiments in white matter hyperintensity segmentation task. We trained a CNN on legacy MR images of brain and evaluated the performance of the domain-adapted network on the same task with images from a different domain. We then compared the performance of the model to the surrogate scenarios where either the same trained network is used or a new network is trained from scratch on the new dataset.The domain-adapted network tuned only by two training examples achieved a Dice score of 0.63 substantially outperforming a similar network trained on the same set of examples from scratch., Comment: 8 pages, 3 figures

We present the integration of the OpenIGTLink network protocol for image-guided therapy (IGT) with the medical prototyping platform MeVisLab. OpenIGTLink is a new, open, simple and extensible network communication protocol for IGT. The protocol provides a standardized mechanism to connect hardware and software by the transfer of coordinate transforms, images, and status messages. MeVisLab is a framework for the development of image processing algorithms and visualization and interaction methods, with a focus on medical imaging. The integration of OpenIGTLink into MeVisLab has been realized by developing a software module using the C++ programming language. As a result, researchers using MeVisLab can interface their software to hardware devices that already support the OpenIGTLink protocol, such as the NDI Aurora magnetic tracking system. In addition, the OpenIGTLink module can also be used to communicate directly with Slicer, a free, open source software package for visualization and image analysis. The integration has been tested with tracker clients available online and a real tracking system., Comment: 18 pages, 5 figures, 1 table, 30 references

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer - a free platform for biomedical research - provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 +/- 5.23% and a Hausdorff Distance of 2.32 +/- 5.23 mm., Comment: 7 pages, 6 figures, 2 tables, 1 equation, 43 references

Gynecologic malignancies are a leading cause of death in women worldwide. Standard treatment for many primary and recurrent gynecologic cancer cases includes a combination of external beam radiation, followed by brachytherapy. Magnetic Resonance Imaging (MRI) is benefitial in diagnostic evaluation, in mapping the tumor location to tailor radiation dose, and in monitoring the tumor response to treatment. Initial studies of MR-guidance in gynecologic brachtherapy demonstrate the ability to optimize tumor coverage and reduce radiation dose to normal tissues, resulting in improved outcomes for patients. In this article we describe a methodology to aid applicator placement and treatment planning for 3 Tesla (3T) MR-guided brachytherapy that was developed specifically for gynecologic cancers. This has been used in 18 cases to date in the Advanced Multimodality Image Guided Operating suite at Brigham and Women's Hospital. It is comprised of state of the art methods for MR imaging, image analysis, and treatment planning. An MR sequence using 3D-balanced steady state free precession in a 3T MR scan was identified as the best sequence for catheter identification with ballooning artifact at the tip. 3D treatment planning was performed using MR images. Item in development include a software module designed to support virtual needle trajectory planning that includes probabilistic bias correction, graph based segmentation, and image registration algorithms. The results demonstrate that 3T MR has a role in gynecologic brachytherapy. These novel developments improve targeted treatment to the tumor while sparing the normal tissues., Comment: 22 pages, 9 figures, 41 references. Epub 2012 Aug 13

In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97\pm3.39%., Comment: 7 pages, 5 figures, 2 tables, 30 references

We present a scale-invariant, template-based segmentation paradigm that sets up a graph and performs a graph cut to separate an object from the background. Typically graph-based schemes distribute the nodes of the graph uniformly and equidistantly on the image, and use a regularizer to bias the cut towards a particular shape. The strategy of uniform and equidistant nodes does not allow the cut to prefer more complex structures, especially when areas of the object are indistinguishable from the background. We propose a solution by introducing the concept of a "template shape" of the target object in which the nodes are sampled non-uniformly and non-equidistantly on the image. We evaluate it on 2D-images where the object's textures and backgrounds are similar, and large areas of the object have the same gray level appearance as the background. We also evaluate it in 3D on 60 brain tumor datasets for neurosurgical planning purposes., Comment: 8 pages, 6 figures, 3 tables, 6 equations, 51 references

We present a rectangle-based segmentation algorithm that sets up a graph and performs a graph cut to separate an object from the background. However, graph-based algorithms distribute the graph's nodes uniformly and equidistantly on the image. Then, a smoothness term is added to force the cut to prefer a particular shape. This strategy does not allow the cut to prefer a certain structure, especially when areas of the object are indistinguishable from the background. We solve this problem by referring to a rectangle shape of the object when sampling the graph nodes, i.e., the nodes are distributed nonuniformly and non-equidistantly on the image. This strategy can be useful, when areas of the object are indistinguishable from the background. For evaluation, we focus on vertebrae images from Magnetic Resonance Imaging (MRI) datasets to support the time consuming manual slice-by-slice segmentation performed by physicians. The ground truth of the vertebrae boundaries were manually extracted by two clinical experts (neurological surgeons) with several years of experience in spine surgery and afterwards compared with the automatic segmentation results of the proposed scheme yielding an average Dice Similarity Coefficient (DSC) of 90.97\pm62.2%., Comment: 13 pages, 17 figures, 2 tables, 3 equations, 42 references