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Magnetic Resonance Fingerprinting (MRF) is a time-efficient approach to quantitative MRI, enabling the mapping of multiple tissue properties from a single, accelerated scan. However, achieving accurate reconstructions remains challenging, particularly in highly accelerated and undersampled acquisitions, which are crucial for reducing scan times. While deep learning techniques have advanced image reconstruction, the recent introduction of diffusion models offers new possibilities for imaging tasks, though their application in the medical field is still emerging. Notably, diffusion models have not yet been explored for the MRF problem. In this work, we propose for the first time a conditional diffusion probabilistic model for MRF image reconstruction. Qualitative and quantitative comparisons on in-vivo brain scan data demonstrate that the proposed approach can outperform established deep learning and compressed sensing algorithms for MRF reconstruction. Extensive ablation studies also explore strategies to improve computational efficiency of our approach., Comment: 12 pages, 5 figures, 2 algorithms

Magnetic resonance spectroscopic imaging is a widely available imaging modality that can non-invasively provide a metabolic profile of the tissue of interest, yet is challenging to integrate clinically. One major reason is the expensive, expert data processing and analysis that is required. Using machine learning to predict MRS-related quantities offers avenues around this problem, but deep learning models bring their own challenges, especially model trust. Current research trends focus primarily on mean error metrics, but comprehensive precision metrics are also needed, e.g. standard deviations, confidence intervals, etc.. This work highlights why more comprehensive error characterization is important and how to improve the precision of CNNs for spectral modeling, a quantitative task. The results highlight advantages and trade-offs of these techniques that should be considered when addressing such regression tasks with CNNs. Detailed insights into the underlying mechanisms of each technique, and how they interact with other techniques, are discussed in depth., Comment: 11 pages, 1 figure, 2 tables

Magnetic Resonance Fingerprinting (MRF) is a time-efficient approach to quantitative MRI for multiparametric tissue mapping. The reconstruction of quantitative maps requires tailored algorithms for removing aliasing artefacts from the compressed sampled MRF acquisitions. Within approaches found in the literature, many focus solely on two-dimensional (2D) image reconstruction, neglecting the extension to volumetric (3D) scans despite their higher relevance and clinical value. A reason for this is that transitioning to 3D imaging without appropriate mitigations presents significant challenges, including increased computational cost and storage requirements, and the need for large amount of ground-truth (artefact-free) data for training. To address these issues, we introduce StoDIP, a new algorithm that extends the ground-truth-free Deep Image Prior (DIP) reconstruction to 3D MRF imaging. StoDIP employs memory-efficient stochastic updates across the multicoil MRF data, a carefully selected neural network architecture, as well as faster nonuniform FFT (NUFFT) transformations. This enables a faster convergence compared against a conventional DIP implementation without these features. Tested on a dataset of whole-brain scans from healthy volunteers, StoDIP demonstrated superior performance over the ground-truth-free reconstruction baselines, both quantitatively and qualitatively., Comment: 10 pages, 2 figures, 1 table, 1 algorithm

The estimation of multi-parametric quantitative maps from Magnetic Resonance Fingerprinting (MRF) compressed sampled acquisitions, albeit successful, remains a challenge due to the high underspampling rate and artifacts naturally occuring during image reconstruction. Whilst state-of-the-art DL methods can successfully address the task, to fully exploit their capabilities they often require training on a paired dataset, in an area where ground truth is seldom available. In this work, we propose a method that combines a deep image prior (DIP) module that, without ground truth and in conjunction with a Bloch consistency enforcing autoencoder, can tackle the problem, resulting in a method faster and of equivalent or better accuracy than DIP-MRF., Comment: 4 pages, 3 figures 1 table, presented at ISBI 2024

Monitoring diseases that affect the brain's structural integrity requires automated analysis of magnetic resonance (MR) images, e.g., for the evaluation of volumetric changes. However, many of the evaluation tools are optimized for analyzing healthy tissue. To enable the evaluation of scans containing pathological tissue, it is therefore required to restore healthy tissue in the pathological areas. In this work, we explore and extend denoising diffusion models for consistent inpainting of healthy 3D brain tissue. We modify state-of-the-art 2D, pseudo-3D, and 3D methods working in the image space, as well as 3D latent and 3D wavelet diffusion models, and train them to synthesize healthy brain tissue. Our evaluation shows that the pseudo-3D model performs best regarding the structural-similarity index, peak signal-to-noise ratio, and mean squared error. To emphasize the clinical relevance, we fine-tune this model on data containing synthetic MS lesions and evaluate it on a downstream brain tissue segmentation task, whereby it outperforms the established FMRIB Software Library (FSL) lesion-filling method.

Accurate image registration is pivotal in biomedical image analysis, where selecting suitable registration algorithms demands careful consideration. While numerous algorithms are available, the evaluation metrics to assess their performance have remained relatively static. This study addresses this challenge by introducing a novel evaluation metric termed Landmark Hit Rate (HitR), which focuses on the clinical relevance of image registration accuracy. Unlike traditional metrics such as Target Registration Error, which emphasize subresolution differences, HitR considers whether registration algorithms successfully position landmarks within defined confidence zones. This paradigm shift acknowledges the inherent annotation noise in medical images, allowing for more meaningful assessments. To equip HitR with label-noise-awareness, we propose defining these confidence zones based on an Inter-rater Variance analysis. Consequently, hit rate curves are computed for varying landmark zone sizes, enabling performance measurement for a task-specific level of accuracy. Our approach offers a more realistic and meaningful assessment of image registration algorithms, reflecting their suitability for clinical and biomedical applications.

Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can acquire high-resolution volumes of the retinal vasculature and aid the diagnosis of ocular, neurological and cardiac diseases. Segmenting the visible blood vessels is a common first step when extracting quantitative biomarkers from these images. Classical segmentation algorithms based on thresholding are strongly affected by image artifacts and limited signal-to-noise ratio. The use of modern, deep learning-based segmentation methods has been inhibited by a lack of large datasets with detailed annotations of the blood vessels. To address this issue, recent work has employed transfer learning, where a segmentation network is trained on synthetic OCTA images and is then applied to real data. However, the previously proposed simulations fail to faithfully model the retinal vasculature and do not provide effective domain adaptation. Because of this, current methods are unable to fully segment the retinal vasculature, in particular the smallest capillaries. In this work, we present a lightweight simulation of the retinal vascular network based on space colonization for faster and more realistic OCTA synthesis. We then introduce three contrast adaptation pipelines to decrease the domain gap between real and artificial images. We demonstrate the superior segmentation performance of our approach in extensive quantitative and qualitative experiments on three public datasets that compare our method to traditional computer vision algorithms and supervised training using human annotations. Finally, we make our entire pipeline publicly available, including the source code, pretrained models, and a large dataset of synthetic OCTA images., Comment: Currently under review

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space.The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment.

Gliomas are the most common type of primary brain tumors. Although gliomas are relatively rare, they are among the deadliest types of cancer, with a survival rate of less than 2 years after diagnosis. Gliomas are challenging to diagnose, hard to treat and inherently resistant to conventional therapy. Years of extensive research to improve diagnosis and treatment of gliomas have decreased mortality rates across the Global North, while chances of survival among individuals in low- and middle-income countries (LMICs) remain unchanged and are significantly worse in Sub-Saharan Africa (SSA) populations. Long-term survival with glioma is associated with the identification of appropriate pathological features on brain MRI and confirmation by histopathology. Since 2012, the Brain Tumor Segmentation (BraTS) Challenge have evaluated state-of-the-art machine learning methods to detect, characterize, and classify gliomas. However, it is unclear if the state-of-the-art methods can be widely implemented in SSA given the extensive use of lower-quality MRI technology, which produces poor image contrast and resolution and more importantly, the propensity for late presentation of disease at advanced stages as well as the unique characteristics of gliomas in SSA (i.e., suspected higher rates of gliomatosis cerebri). Thus, the BraTS-Africa Challenge provides a unique opportunity to include brain MRI glioma cases from SSA in global efforts through the BraTS Challenge to develop and evaluate computer-aided-diagnostic (CAD) methods for the detection and characterization of glioma in resource-limited settings, where the potential for CAD tools to transform healthcare are more likely., Comment: arXiv admin note: text overlap with arXiv:2107.02314

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge., Comment: 14 pages, 6 figures

Even though simultaneous optimization of similarity metrics is a standard procedure in the field of semantic segmentation, surprisingly, this is much less established for image registration. To help closing this gap in the literature, we investigate in a complex multi-modal 3D setting whether simultaneous optimization of registration metrics, here implemented by means of primitive summation, can benefit image registration. We evaluate two challenging datasets containing collections of pre- to post-operative and pre- to intra-operative MR images of glioma. Employing the proposed optimization, we demonstrate improved registration accuracy in terms of TRE on expert neuroradiologists' landmark annotations.

Optical coherence tomography angiography (OCTA) can non-invasively image the eye's circulatory system. In order to reliably characterize the retinal vasculature, there is a need to automatically extract quantitative metrics from these images. The calculation of such biomarkers requires a precise semantic segmentation of the blood vessels. However, deep-learning-based methods for segmentation mostly rely on supervised training with voxel-level annotations, which are costly to obtain. In this work, we present a pipeline to synthesize large amounts of realistic OCTA images with intrinsically matching ground truth labels; thereby obviating the need for manual annotation of training data. Our proposed method is based on two novel components: 1) a physiology-based simulation that models the various retinal vascular plexuses and 2) a suite of physics-based image augmentations that emulate the OCTA image acquisition process including typical artifacts. In extensive benchmarking experiments, we demonstrate the utility of our synthetic data by successfully training retinal vessel segmentation algorithms. Encouraged by our method's competitive quantitative and superior qualitative performance, we believe that it constitutes a versatile tool to advance the quantitative analysis of OCTA images., Comment: Accepted at MICCAI 2022

Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of $0.9260\pm 0.18 \%$ on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by ischemic injuries. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determine the choice of stroke care model - that is the decision to transport or treat eligible patients immediately. Though there exist several imaging methods and grading criteria for quantifying collateral blood flow, the actual grading is mostly done through manual inspection of the acquired images. This approach is associated with a number of challenges. First, it is time-consuming - the clinician needs to scan through several slices of images to ascertain the region of interest before deciding on what severity grade to assign to a patient. Second, there is a high tendency for bias and inconsistency in the final grade assigned to a patient depending on the experience level of the clinician. We present a deep learning approach to predicting collateral flow grading in stroke patients based on radiomic features extracted from MR perfusion data. First, we formulate a region of interest detection task as a reinforcement learning problem and train a deep learning network to automatically detect the occluded region within the 3D MR perfusion volumes. Second, we extract radiomic features from the obtained region of interest through local image descriptors and denoising auto-encoders. Finally, we apply a convolutional neural network and other machine learning classifiers to the extracted radiomic features to automatically predict the collateral flow grading of the given patient volume as one of three severity classes - no flow (0), moderate flow (1), and good flow (2)...

Fast and accurate solutions of time-dependent partial differential equations (PDEs) are of pivotal interest to many research fields, including physics, engineering, and biology. Generally, implicit/semi-implicit schemes are preferred over explicit ones to improve stability and correctness. However, existing semi-implicit methods are usually iterative and employ a general-purpose solver, which may be sub-optimal for a specific class of PDEs. In this paper, we propose a neural solver to learn an optimal iterative scheme in a data-driven fashion for any class of PDEs. Specifically, we modify a single iteration of a semi-implicit solver using a deep neural network. We provide theoretical guarantees for the correctness and convergence of neural solvers analogous to conventional iterative solvers. In addition to the commonly used Dirichlet boundary condition, we adopt a diffuse domain approach to incorporate a diverse type of boundary conditions, e.g., Neumann. We show that the proposed neural solver can go beyond linear PDEs and applies to a class of non-linear PDEs, where the non-linear component is non-stiff. We demonstrate the efficacy of our method on 2D and 3D scenarios. To this end, we show how our model generalizes to parameter settings, which are different from training; and achieves faster convergence than semi-implicit schemes.

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph ., Comment: Thirty-fifth Conference on Neural Information Processing Systems Datasets and Benchmarks Track

Self-supervision has demonstrated to be an effective learning strategy when training target tasks on small annotated data-sets. While current research focuses on creating novel pretext tasks to learn meaningful and reusable representations for the target task, these efforts obtain marginal performance gains compared to fully-supervised learning. Meanwhile, little attention has been given to study the robustness of networks trained in a self-supervised manner. In this work, we demonstrate that networks trained via self-supervised learning have superior robustness and generalizability compared to fully-supervised learning in the context of medical imaging. Our experiments on pneumonia detection in X-rays and multi-organ segmentation in CT yield consistent results exposing the hidden benefits of self-supervision for learning robust feature representations.

Novel multimodal imaging methods are capable of generating extensive, super high resolution datasets for preclinical research. Yet, a massive lack of annotations prevents the broad use of deep learning to analyze such data. So far, existing generative models fail to mitigate this problem because of frequent labeling errors. In this paper, we introduce a novel generative method which leverages real anatomical information to generate realistic image-label pairs of tumours. We construct a dual-pathway generator, for the anatomical image and label, trained in a cycle-consistent setup, constrained by an independent, pretrained segmentor. The generated images yield significant quantitative improvement compared to existing methods. To validate the quality of synthesis, we train segmentation networks on a dataset augmented with the synthetic data, substantially improving the segmentation over baseline.

This paper presents a novel yet efficient defense framework for segmentation models against adversarial attacks in medical imaging. In contrary to the defense methods against adversarial attacks for classification models which widely are investigated, such defense methods for segmentation models has been less explored. Our proposed method can be used for any deep learning models without revising the target deep learning models, as well as can be independent of adversarial attacks. Our framework consists of a frequency domain converter, a detector, and a reformer. The frequency domain converter helps the detector detects adversarial examples by using a frame domain of an image. The reformer helps target models to predict more precisely. We have experiments to empirically show that our proposed method has a better performance compared to the existing defense method.

Designing of a cranial implant needs a 3D understanding of the complete skull shape. Thus, taking a 2D approach is sub-optimal, since a 2D model lacks a holistic 3D view of both the defective and healthy skulls. Further, loading the whole 3D skull shapes at its original image resolution is not feasible in commonly available GPUs. To mitigate these issues, we propose a fully convolutional network composed of two subnetworks. The first subnetwork is designed to complete the shape of the downsampled defective skull. The second subnetwork upsamples the reconstructed shape slice-wise. We train the 3D and 2D networks together end-to-end, with a hierarchical loss function. Our proposed solution accurately predicts a high-resolution 3D implant in the challenge test case in terms of dice-score and the Hausdorff distance.

Osteoporotic vertebral fractures have a severe impact on patients' overall well-being but are severely under-diagnosed. These fractures present themselves at various levels of severity measured using the Genant's grading scale. Insufficient annotated datasets, severe data-imbalance, and minor difference in appearances between fractured and healthy vertebrae make naive classification approaches result in poor discriminatory performance. Addressing this, we propose a representation learning-inspired approach for automated vertebral fracture detection, aimed at learning latent representations efficient for fracture detection. Building on state-of-art metric losses, we present a novel Grading Loss for learning representations that respect Genant's fracture grading scheme. On a publicly available spine dataset, the proposed loss function achieves a fracture detection F1 score of 81.5%, a 10% increase over a naive classification baseline., Comment: To be presented at MICCAI 2020

The treatment of degenerative spinal disorders requires an understanding of the individual spinal anatomy and curvature in 3D. An upright spinal pose (i.e. standing) under natural weight bearing is crucial for such bio-mechanical analysis. 3D volumetric imaging modalities (e.g. CT and MRI) are performed in patients lying down. On the other hand, radiographs are captured in an upright pose, but result in 2D projections. This work aims to integrate the two realms, i.e. it combines the upright spinal curvature from radiographs with the 3D vertebral shape from CT imaging for synthesizing an upright 3D model of spine, loaded naturally. Specifically, we propose a novel neural network architecture working vertebra-wise, termed \emph{TransVert}, which takes orthogonal 2D radiographs and infers the spine's 3D posture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of $95.52\%$, indicating an almost perfect 2D-to-3D domain translation. Deploying our model on clinical radiographs, we successfully synthesise full-3D, upright, patient-specific spine models for the first time.

Robust localization of organs in computed tomography scans is a constant pre-processing requirement for organ-specific image retrieval, radiotherapy planning, and interventional image analysis. In contrast to current solutions based on exhaustive search or region proposals, which require large amounts of annotated data, we propose a deep reinforcement learning approach for organ localization in CT. In this work, an artificial agent is actively self-taught to localize organs in CT by learning from its asserts and mistakes. Within the context of reinforcement learning, we propose a novel set of actions tailored for organ localization in CT. Our method can use as a plug-and-play module for localizing any organ of interest. We evaluate the proposed solution on the public VISCERAL dataset containing CT scans with varying fields of view and multiple organs. We achieved an overall intersection over union of 0.63, an absolute median wall distance of 2.25 mm, and a median distance between centroids of 3.65 mm., Comment: Accepted paper in MIDL 2020

Magnetic Resonance Fingerprinting (MRF) enables the simultaneous quantification of multiple properties of biological tissues. It relies on a pseudo-random acquisition and the matching of acquired signal evolutions to a precomputed dictionary. However, the dictionary is not scalable to higher-parametric spaces, limiting MRF to the simultaneous mapping of only a small number of parameters (proton density, T1 and T2 in general). Inspired by diffusion-weighted SSFP imaging, we present a proof-of-concept of a novel MRF sequence with embedded diffusion-encoding gradients along all three axes to efficiently encode orientational diffusion and T1 and T2 relaxation. We take advantage of a convolutional neural network (CNN) to reconstruct multiple quantitative maps from this single, highly undersampled acquisition. We bypass expensive dictionary matching by learning the implicit physical relationships between the spatiotemporal MRF data and the T1, T2 and diffusion tensor parameters. The predicted parameter maps and the derived scalar diffusion metrics agree well with state-of-the-art reference protocols. Orientational diffusion information is captured as seen from the estimated primary diffusion directions. In addition to this, the joint acquisition and reconstruction framework proves capable of preserving tissue abnormalities in multiple sclerosis lesions.

Accurate segmentation of tubular, network-like structures, such as vessels, neurons, or roads, is relevant to many fields of research. For such structures, the topology is their most important characteristic; particularly preserving connectedness: in the case of vascular networks, missing a connected vessel entirely alters the blood-flow dynamics. We introduce a novel similarity measure termed centerlineDice (short clDice), which is calculated on the intersection of the segmentation masks and their (morphological) skeleta. We theoretically prove that clDice guarantees topology preservation up to homotopy equivalence for binary 2D and 3D segmentation. Extending this, we propose a computationally efficient, differentiable loss function (soft-clDice) for training arbitrary neural segmentation networks. We benchmark the soft-clDice loss on five public datasets, including vessels, roads and neurons (2D and 3D). Training on soft-clDice leads to segmentation with more accurate connectivity information, higher graph similarity, and better volumetric scores., Comment: * The authors Suprosanna Shit and Johannes C. Paetzold contributed equally to the work

Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision-support systems for diagnosis, surgery planning, and population-based analysis on spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms towards labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel-level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the the results of this evaluation and further investigate the performance-variation at vertebra-level, scan-level, and at different fields-of-view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The content and code concerning VerSe can be accessed at: https://github.com/anjany/verse., Comment: Challenge report for the VerSe 2019 and 2020. Published in Medical Image Analysis (DOI: https://doi.org/10.1016/j.media.2021.102166)

Novel methods for quantitative, transient-state multiparametric imaging are increasingly being demonstrated for assessment of disease and treatment efficacy. Here, we build on these by assessing the most common Non-Cartesian readout trajectories (2D/3D radials and spirals), demonstrating efficient anti-aliasing with a k-space view-sharing technique, and proposing novel methods for parameter inference with neural networks that incorporate the estimation of proton density. Our results show good agreement with gold standard and phantom references for all readout trajectories at 1.5T and 3T. Parameters inferred with the neural network were within 6.58% difference from the parameters inferred with a high-resolution dictionary. Concordance correlation coefficients were above 0.92 and the normalized root mean squared error ranged between 4.2% - 12.7% with respect to gold-standard phantom references for T1 and T2. In vivo acquisitions demonstrate sub-millimetric isotropic resolution in under five minutes with reconstruction and inference times < 7 minutes. Our 3D quantitative transient-state imaging approach could enable high-resolution multiparametric tissue quantification within clinically acceptable acquisition and reconstruction times., Comment: 43 pages, 12 Figures, 5 Tables

We propose an auto-encoding network architecture for point clouds (PC) capable of extracting shape signatures without supervision. Building on this, we (i) design a loss function capable of modelling data variance on PCs which are unstructured, and (ii) regularise the latent space as in a variational auto-encoder, both of which increase the auto-encoders' descriptive capacity while making them probabilistic. Evaluating the reconstruction quality of our architectures, we employ them for detecting vertebral fractures without any supervision. By learning to efficiently reconstruct only healthy vertebrae, fractures are detected as anomalous reconstructions. Evaluating on a dataset containing $\sim$1500 vertebrae, we achieve area-under-ROC curve of $>$75%, without using intensity-based features., Comment: Accepted at Medical Image Computing and Computer-Assisted Intervention (MICCAI), 2019; JSK and BHM are joint supervising authors

Mammogram is the most effective imaging modality for the mass lesion detection of breast cancer at the early stage. The information from the two paired views (i.e., medio-lateral oblique and cranio-caudal) are highly relational and complementary, and this is crucial for doctors' decisions in clinical practice. However, existing mass detection methods do not consider jointly learning effective features from the two relational views. To address this issue, this paper proposes a novel mammogram mass detection framework, termed Cross-View Relation Region-based Convolutional Neural Networks (CVR-RCNN). The proposed CVR-RCNN is expected to capture the latent relation information between the corresponding mass region of interests (ROIs) from the two paired views. Evaluations on a new large-scale private dataset and a public mammogram dataset show that the proposed CVR-RCNN outperforms existing state-of-the-art mass detection methods. Meanwhile, our experimental results suggest that incorporating the relation information across two views helps to train a superior detection model, which is a promising avenue for mammogram mass detection.

Purpose: To use and test a labelling algorithm that operates on two-dimensional (2D) reformations, rather than three-dimensional (3D) data to locate and identify vertebrae. Methods: We improved the Btrfly Net (described by Sekuboyina et al) that works on sagittal and coronal maximum intensity projections (MIP) and augmented it with two additional components: spine-localization and adversarial a priori-learning. Furthermore, we explored two variants of adversarial training schemes that incorporated the anatomical a priori knowledge into the Btrfly Net. We investigated the superiority of the proposed approach for labelling vertebrae on three datasets: a public benchmarking dataset of 302 CT scans and two in-house datasets with a total of 238 CT scans. We employed Wilcoxon signed-rank test to compute the statistical significance of the improvement in performance observed due to various architectural components in our approach. Results: On the public dataset, our approach using the described Btrfly(pe-eb) network performed on par with current state-of-the-art methods achieving a statistically significant (p < .001) vertebrae identification rate of 88.5+/-0.2 % and localization distances of less than 7-mm. On the in-house datasets that had a higher inter-scan data variability, we obtained an identification rate of 85.1+/-1.2%. Conclusion: An identification performance comparable to existing 3D approaches was achieved when labelling vertebrae on 2D MIPs. The performance was further improved using the proposed adversarial training regime that effectively enforced local spine a priori knowledge during training. Lastly, spine-localization increased the generalizability of our approach by homogenizing the content in the MIPs., Comment: Published in Radiology:AI

Magnetic resonance imaging (MRI) is a remarkably powerful diagnostic technique: it generates wide-ranging information for the non-invasive study of tissue anatomy and physiology. Complementary data is normally obtained in separate measurements, either as contrast-weighted images, which are fast and simple to acquire, or as quantitative parametric maps, which offer an absolute quantification of underlying biophysical effects, such as relaxation times or flow. Here, we demonstrate how to acquire and reconstruct data in a transient-state with a dual purpose: 1 - to generate contrast-weighted images that can be adjusted to emphasise clinically relevant image biomarkers; exemplified with signal modulation according to flow to obtain angiography information, and 2 - to simultaneously infer multiple quantitative parameters with a single, highly accelerated acquisition. This is a achieved by introducing three novel elements: a model that accounts for flowing blood, a method for sequence design that incorporates both parameter encoding and signal contrast, and the reconstruction of temporally resolved contrast-weighted images. From these images we simultaneously obtain angiography projections and multiple quantitative maps. By doing so, we increase the amount of clinically relevant data without adding measurement time, creating new dimensions for biomarker exploration and adding value to MR examinations for patients and clinicians alike.

Early diagnosis of pulmonary nodules (PNs) can improve the survival rate of patients and yet is a challenging task for radiologists due to the image noise and artifacts in computed tomography (CT) images. In this paper, we propose a novel and effective abnormality detector implementing the attention mechanism and group convolution on 3D single-shot detector (SSD) called group-attention SSD (GA-SSD). We find that group convolution is effective in extracting rich context information between continuous slices, and attention network can learn the target features automatically. We collected a large-scale dataset that contained 4146 CT scans with annotations of varying types and sizes of PNs (even PNs smaller than 3mm were annotated). To the best of our knowledge, this dataset is the largest cohort with relatively complete annotations for PNs detection. Our experimental results show that the proposed group-attention SSD outperforms the classic SSD framework as well as the state-of-the-art 3DCNN, especially on some challenging lesion types.

For many segmentation tasks, especially for the biomedical image, the topological prior is vital information which is useful to exploit. The containment/nesting is a typical inter-class geometric relationship. In the MICCAI Brain tumor segmentation challenge, with its three hierarchically nested classes 'whole tumor', 'tumor core', 'active tumor', the nested classes relationship is introduced into the 3D-residual-Unet architecture. The network comprises a context aggregation pathway and a localization pathway, which encodes increasingly abstract representation of the input as going deeper into the network, and then recombines these representations with shallower features to precisely localize the interest domain via a localization path. The nested-class-prior is combined by proposing the multi-class activation function and its corresponding loss function. The model is trained on the training dataset of Brats2018, and 20% of the dataset is regarded as the validation dataset to determine parameters. When the parameters are fixed, we retrain the model on the whole training dataset. The performance achieved on the validation leaderboard is 86%, 77% and 72% Dice scores for the whole tumor, enhancing tumor and tumor core classes without relying on ensembles or complicated post-processing steps. Based on the same start-of-the-art network architecture, the accuracy of nested-class (enhancing tumor) is reasonably improved from 69% to 72% compared with the traditional Softmax-based method which blind to topological prior., Comment: 12pages first version

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., Comment: Article published in Nature Communications: https://rdcu.be/bRmNr

Magnetic Resonance Spectroscopic Imaging (MRSI) is a clinical imaging modality for measuring tissue metabolite levels in-vivo. An accurate estimation of spectral parameters allows for better assessment of spectral quality and metabolite concentration levels. The current gold standard quantification method is the LCModel - a commercial fitting tool. However, this fails for spectra having poor signal-to-noise ratio (SNR) or a large number of artifacts. This paper introduces a framework based on random forest regression for accurate estimation of the output parameters of a model based analysis of MR spectroscopy data. The goal of our proposed framework is to learn the spectral features from a training set comprising of different variations of both simulated and in-vivo brain spectra and then use this learning for the subsequent metabolite quantification. Experiments involve training and testing on simulated and in-vivo human brain spectra. We estimate parameters such as concentration of metabolites and compare our results with that from the LCModel.

Arterial spin labeling (ASL) allows to quantify the cerebral blood flow (CBF) by magnetic labeling of the arterial blood water. ASL is increasingly used in clinical studies due to its noninvasiveness, repeatability and benefits in quantification. However, ASL suffers from an inherently low-signal-to-noise ratio (SNR) requiring repeated measurements of control/spin-labeled (C/L) pairs to achieve a reasonable image quality, which in return increases motion sensitivity. This leads to clinically prolonged scanning times increasing the risk of motion artifacts. Thus, there is an immense need of advanced imaging and processing techniques in ASL. In this paper, we propose a novel deep learning based approach to improve the perfusion-weighted image quality obtained from a subset of all available pairwise C/L subtractions. Specifically, we train a deep fully convolutional network (FCN) to learn a mapping from noisy perfusion-weighted image and its subtraction (residual) from the clean image. Additionally, we incorporate the CBF estimation model in the loss function during training, which enables the network to produce high quality images while simultaneously enforcing the CBF estimates to be as close as reference CBF values. Extensive experiments on synthetic and clinical ASL datasets demonstrate the effectiveness of our method in terms of improved ASL image quality, accurate CBF parameter estimation and considerably small computation time during testing., Comment: Accepted at MICCAI 2018. 9 pages, 4 figures, 1 table

Dynamic contrast-enhanced (DCE) MRI is an evolving imaging technique that provides a quantitative measure of pharmacokinetic (PK) parameters in body tissues, in which series of T1-weighted images are collected following the administration of a paramagnetic contrast agent. Unfortunately, in many applications, conventional clinical DCE-MRI suffers from low spatiotemporal resolution and insufficient volume coverage. In this paper, we propose a novel deep learning based approach to directly estimate the PK parameters from undersampled DCE-MRI data. Specifically, we design a custom loss function where we incorporate a forward physical model that relates the PK parameters to corrupted image-time series obtained due to subsampling in k-space. This allows the network to directly exploit the knowledge of true contrast agent kinetics in the training phase, and hence provide more accurate restoration of PK parameters. Experiments on clinical brain DCE datasets demonstrate the efficacy of our approach in terms of fidelity of PK parameter reconstruction and significantly faster parameter inference compared to a model-based iterative reconstruction method., Comment: Accepted at MICCAI 2018. 9 pages, 6 figures

For many biological image segmentation tasks, including topological knowledge, such as the nesting of classes, can greatly improve results. However, most `out-of-the-box' CNN models are still blind to such prior information. In this paper, we propose a novel approach to encode this information, through a multi-level activation layer and three compatible losses. We benchmark all of them on nuclei segmentation in bright-field microscopy cell images from the 2018 Data Science Bowl challenge, offering an exemplary segmentation task with cells and nested subcellular structures. Our scheme greatly speeds up learning, and outperforms standard multi-class classification with soft-max activation and a previously proposed method stemming from it, improving the Dice score significantly (p-values<0.007). Our approach is conceptually simple, easy to implement and can be integrated in any CNN architecture. It can be generalized to a higher number of classes, with or without further relations of containment., Comment: Accepted for the BioImage Computing 2018 workshop, ECCV conference

Robust localisation and identification of vertebrae is essential for automated spine analysis. The contribution of this work to the task is two-fold: (1) Inspired by the human expert, we hypothesise that a sagittal and coronal reformation of the spine contain sufficient information for labelling the vertebrae. Thereby, we propose a butterfly-shaped network architecture (termed Btrfly Net) that efficiently combines the information across reformations. (2) Underpinning the Btrfly net, we present an energy-based adversarial training regime that encodes local spine structure as an anatomical prior into the network, thereby enabling it to achieve state-of-art performance in all standard metrics on a benchmark dataset of 302 scans without any post-processing during inference., Comment: Published as conference paper in Medical Image Computing and Computer Assisted Intervention - MICCAI 2018

We present DeepVesselNet, an architecture tailored to the challenges faced when extracting vessel networks or trees and corresponding features in 3-D angiographic volumes using deep learning. We discuss the problems of low execution speed and high memory requirements associated with full 3-D convolutional networks, high-class imbalance arising from the low percentage of vessel voxels, and unavailability of accurately annotated training data - and offer solutions as the building blocks of DeepVesselNet. First, we formulate 2-D orthogonal cross-hair filters which make use of 3-D context information at a reduced computational burden. Second, we introduce a class balancing cross-entropy loss function with false positive rate correction to handle the high-class imbalance and high false positive rate problems associated with existing loss functions. Finally, we generate synthetic dataset using a computational angiogenesis model capable of generating vascular trees under physiological constraints on local network structure and topology and use these data for transfer learning. DeepVesselNet is optimized for segmenting and analyzing vessels, and we test the performance on a range of angiographic volumes including clinical MRA data of the human brain, as well as X-ray tomographic microscopy scans of the rat brain. Our experiments show that, by replacing 3-D filters with cross-hair filters in our network, we achieve over 23% improvement in speed, lower memory footprint, lower network complexity which prevents overfitting and comparable accuracy (with a Cox-Wilcoxon paired sample significance test p-value of 0.07 when compared to full 3-D filters). Our class balancing metric is crucial for training the network and transfer learning with synthetic data is an efficient, robust, and very generalizable approach leading to a network that excels in a variety of angiography segmentation tasks., Comment: 13 pages

Feature extraction is a very crucial task in image and pixel (voxel) classification and regression in biomedical image modeling. In this work we present a machine learning based feature extraction scheme based on inception models for pixel classification tasks. We extract features under multi-scale and multi-layer schemes through convolutional operators. Layers of Fully Convolutional Network are later stacked on this feature extraction layers and trained end-to-end for the purpose of classification. We test our model on the DRIVE and STARE public data sets for the purpose of segmentation and centerline detection and it out performs most existing hand crafted or deterministic feature schemes found in literature. We achieve an average maximum Dice of 0.85 on the DRIVE data set which out performs the scores from the second human annotator of this data set. We also achieve an average maximum Dice of 0.85 and kappa of 0.84 on the STARE data set. Though these datasets are mainly 2-D we also propose ways of extending this feature extraction scheme to handle 3-D datasets., Comment: 9 pages

The segmentation of liver lesions is crucial for detection, diagnosis and monitoring progression of liver cancer. However, design of accurate automated methods remains challenging due to high noise in CT scans, low contrast between liver and lesions, as well as large lesion variability. We propose a 3D automatic, unsupervised method for liver lesions segmentation using a phase separation approach. It is assumed that liver is a mixture of two phases: healthy liver and lesions, represented by different image intensities polluted by noise. The Cahn-Hilliard equation is used to remove the noise and separate the mixture into two distinct phases with well-defined interfaces. This simplifies the lesion detection and segmentation task drastically and enables to segment liver lesions by thresholding the Cahn-Hilliard solution. The method was tested on 3Dircadb and LITS dataset.

Multi-class segmentation of vertebrae is a non-trivial task mainly due to the high correlation in the appearance of adjacent vertebrae. Hence, such a task calls for the consideration of both global and local context. Based on this motivation, we propose a two-staged approach that, given a computed tomography dataset of the spine, segments the five lumbar vertebrae and simultaneously labels them. The first stage employs a multi-layered perceptron performing non-linear regression for locating the lumbar region using the global context. The second stage, comprised of a fully-convolutional deep network, exploits the local context in the localised lumbar region to segment and label the lumbar vertebrae in one go. Aided with practical data augmentation for training, our approach is highly generalisable, capable of successfully segmenting both healthy and abnormal vertebrae (fractured and scoliotic spines). We consistently achieve an average Dice coefficient of over 90 percent on a publicly available dataset of the xVertSeg segmentation challenge of MICCAI 2016. This is particularly noteworthy because the xVertSeg dataset is beset with severe deformities in the form of vertebral fractures and scoliosis.

Lineage tracing, the joint segmentation and tracking of living cells as they move and divide in a sequence of light microscopy images, is a challenging task. Jug et al. have proposed a mathematical abstraction of this task, the moral lineage tracing problem (MLTP), whose feasible solutions define both a segmentation of every image and a lineage forest of cells. Their branch-and-cut algorithm, however, is prone to many cuts and slow convergence for large instances. To address this problem, we make three contributions: (i) we devise the first efficient primal feasible local search algorithms for the MLTP, (ii) we improve the branch-and-cut algorithm by separating tighter cutting planes and by incorporating our primal algorithms, (iii) we show in experiments that our algorithms find accurate solutions on the problem instances of Jug et al. and scale to larger instances, leveraging moral lineage tracing to practical significance., Comment: Accepted at ICCV 2017

Automatic segmentation of the liver and its lesion is an important step towards deriving quantitative biomarkers for accurate clinical diagnosis and computer-aided decision support systems. This paper presents a method to automatically segment liver and lesions in CT abdomen images using cascaded fully convolutional neural networks (CFCNs) and dense 3D conditional random fields (CRFs). We train and cascade two FCNs for a combined segmentation of the liver and its lesions. In the first step, we train a FCN to segment the liver as ROI input for a second FCN. The second FCN solely segments lesions from the predicted liver ROIs of step 1. We refine the segmentations of the CFCN using a dense 3D CRF that accounts for both spatial coherence and appearance. CFCN models were trained in a 2-fold cross-validation on the abdominal CT dataset 3DIRCAD comprising 15 hepatic tumor volumes. Our results show that CFCN-based semantic liver and lesion segmentation achieves Dice scores over 94% for liver with computation times below 100s per volume. We experimentally demonstrate the robustness of the proposed method as a decision support system with a high accuracy and speed for usage in daily clinical routine., Comment: Accepted at MICCAI 2016. Source code available on https://github.com/IBBM/Cascaded-FCN

Several important tasks in medical image analysis can be stated in the form of an optimization problem whose feasible solutions are connected subgraphs. Examples include the reconstruction of neural or vascular structures under connectedness constraints. We discuss the minimum cost connected subgraph (MCCS) problem and its approximations from the perspective of medical applications. We propose a) objective-dependent constraints and b) novel constraint generation schemes to solve this optimization problem exactly by means of a branch-and-cut algorithm. These are shown to improve scalability and allow us to solve instances of two medical benchmark datasets to optimality for the first time. This enables us to perform a quantitative comparison between exact and approximative algorithms, where we identify the geodesic tree algorithm as an excellent alternative to exact inference on the examined datasets., Comment: accepted at MICCAI 2016