Evaluating a Periapical Lesion Detection CNN on a Clinically Representative CBCT Dataset-A Validation Study.

The aim of this validation study was to comprehensively evaluate the performance and generalization capability of a deep learning-based periapical lesion detection algorithm on a clinically representative cone-beam computed tomography (CBCT) dataset and test for non-inferiority. The evaluation involved 195 CBCT images of adult upper and lower jaws, where sensitivity and specificity metrics were calculated for all teeth, stratified by jaw, and stratified by tooth type. Furthermore, each lesion was assigned a periapical index score based on its size to enable a score-based evaluation. Non-inferiority tests were conducted with proportions of 90% for sensitivity and 82% for specificity. The algorithm achieved an overall sensitivity of 86.7% and a specificity of 84.3%. The non-inferiority test indicated the rejection of the null hypothesis for specificity but not for sensitivity. However, when excluding lesions with a periapical index score of one (i.e., very small lesions), the sensitivity improved to 90.4%. Despite the challenges posed by the dataset, the algorithm demonstrated promising results. Nevertheless, further improvements are needed to enhance the algorithm's robustness, particularly in detecting very small lesions and the handling of artifacts and outliers commonly encountered in real-world clinical scenarios.

Fast and Low-GPU-memory abdomen CT organ segmentation: The FLARE challenge.

Automatic segmentation of abdominal organs in CT scans plays an important role in clinical practice. However, most existing benchmarks and datasets only focus on segmentation accuracy, while the model efficiency and its accuracy on the testing cases from different medical centers have not been evaluated. To comprehensively benchmark abdominal organ segmentation methods, we organized the first Fast and Low GPU memory Abdominal oRgan sEgmentation (FLARE) challenge, where the segmentation methods were encouraged to achieve high accuracy on the testing cases from different medical centers, fast inference speed, and low GPU memory consumption, simultaneously. The winning method surpassed the existing state-of-the-art method, achieving a 19× faster inference speed and reducing the GPU memory consumption by 60% with comparable accuracy. We provide a summary of the top methods, make their code and Docker containers publicly available, and give practical suggestions on building accurate and efficient abdominal organ segmentation models. The FLARE challenge remains open for future submissions through a live platform for benchmarking further methodology developments at https://flare.grand-challenge.org/.

Automatic Detection of Periapical Osteolytic Lesions on Cone-beam Computed Tomography Using Deep Convolutional Neuronal Networks.

INTRODUCTION: Cone-beam computed tomography (CBCT) is an essential diagnostic tool in oral radiology. Radiolucent periapical lesions (PALs) represent the most frequent jaw lesions. However, the description, interpretation, and documentation of radiological findings, especially incidental findings, are time-consuming and resource-intensive, requiring a high degree of expertise. To improve quality, dentists may use artificial intelligence in the form of deep learning tools. This study was conducted to develop and validate a deep convolutional neuronal network for the automated detection of osteolytic PALs in CBCT data sets. METHODS: CBCT data sets from routine clinical operations (maxilla, mandible, or both) performed from January to October 2020 were retrospectively screened and selected. A 2-step approach was used for automatic PAL detection. First, tooth localization and identification were performed using the SpatialConfiguration-Net based on heatmap regression. Second, binary segmentation of lesions was performed using a modified U-Net architecture. A total of 144 CBCT images were used to train and test the networks. The method was evaluated using the 4-fold cross-validation technique. RESULTS: The success detection rate of the tooth localization network ranged between 72.6% and 97.3%, whereas the sensitivity and specificity values of lesion detection were 97.1% and 88.0%, respectively. CONCLUSIONS: Although PALs showed variations in appearance, size, and shape in the CBCT data set and a high imbalance existed between teeth with and without PALs, the proposed fully automated method provided excellent results compared with related literature.

Anatomy-Aware Inference of the 3D Standing Spine Posture from 2D Radiographs.

An important factor for the development of spinal degeneration, pain and the outcome of spinal surgery is known to be the balance of the spine. It must be analyzed in an upright, standing position to ensure physiological loading conditions and visualize load-dependent deformations. Despite the complex 3D shape of the spine, this analysis is currently performed using 2D radiographs, as all frequently used 3D imaging techniques require the patient to be scanned in a prone position. To overcome this limitation, we propose a deep neural network to reconstruct the 3D spinal pose in an upright standing position, loaded naturally. Specifically, we propose a novel neural network architecture, which takes orthogonal 2D radiographs and infers the spine's 3D posture using vertebral shape priors. In this work, we define vertebral shape priors using an atlas and a spine shape prior, incorporating both into our proposed network architecture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of 0.95, indicating an almost perfect 2D-to-3D domain translation. Validating the reconstruction accuracy of a 3D standing spine on real data is infeasible due to the lack of a valid ground truth. Hence, we design a novel experiment for this purpose, using an orientation invariant distance metric, to evaluate our model's ability to synthesize full-3D, upright, and patient-specific spine models. We compare the synthesized spine shapes from clinical upright standing radiographs to the same patient's 3D spinal posture in the prone position from CT.

Uncertainty estimation and explainability in deep learning-based age estimation of the human brain: Results from the German National Cohort MRI study.

Brain ageing is a complex neurobiological process associated with morphological changes that can be assessed on MRI scans. Recently, Deep learning (DL)-based approaches have been proposed for the prediction of chronological brain age from MR images yielding high accuracy. These approaches, however, usually do not address quantification of uncertainty and, therefore, intrinsic physiological variability. Considering uncertainty is essential for the interpretation of the difference between predicted and chronological age. In addition, DL-based models lack in explainability compared to classical approaches like voxel-based morphometry. In this study, we aim to address both, modeling uncertainty and providing visual explanations to explore physiological patterns in brain ageing. T1-weighted brain MRI datasets of 10691 participants of the German National Cohort Study, drawn from the general population, were included in this study (chronological age from 20 to 72 years). A regression model based on a 3D Convolutional Neural Network taking into account aleatoric noise was implemented for global as well as regional brain age estimation. We observed high overall accuracy of global brain age estimation with a mean absolute error of 3.2 ±â€¯2.5 years and mean uncertainty of 2.9 ±â€¯0.6 years. Regional brain age estimation revealed higher estimation accuracy and lower uncertainty in central compared to peripheral brain regions. Visual explanations illustrating the importance of brain sub-regions were generated using Grad-CAM: the derived saliency maps showed a high relevance of the lateral and third ventricles, the insular lobe as well as parts of the basal ganglia and the internal capsule.

VerSe: A Vertebrae labelling and segmentation benchmark for multi-detector CT images.

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 of 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 tackling the 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 results of this evaluation and further investigate the performance variation at the vertebra level, scan level, and 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 VerSe content and code can be accessed at: https://github.com/anjany/verse.

A Framework for the generation of digital twins of cardiac electrophysiology from clinical 12-leads ECGs.

Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, safe and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and bio-physically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (<4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.

Automated age estimation from MRI volumes of the hand.

Highly relevant for both clinical and legal medicine applications, the established radiological methods for estimating unknown age in children and adolescents are based on visual examination of bone ossification in X-ray images of the hand. Our group has initiated the development of fully automatic age estimation methods from 3D MRI scans of the hand, in order to simultaneously overcome the problems of the radiological methods including (1) exposure to ionizing radiation, (2) necessity to define new, MRI specific staging systems, and (3) subjective influence of the examiner. The present work provides a theoretical background for understanding the nonlinear regression problem of biological age estimation and chronological age approximation. Based on this theoretical background, we comprehensively evaluate machine learning methods (random forests, deep convolutional neural networks) with different simplifications of the image information used as an input for learning. Trained on a large dataset of 328 MR images, we compare the performance of the different input strategies and demonstrate unprecedented results. For estimating biological age, we obtain a mean absolute error of 0.37 ±â€¯0.51 years for the age range of the subjects  ≤  18 years, i.e. where bone ossification has not yet saturated. Finally, we validate our findings by adapting our best performing method to 2D images and applying it to a publicly available dataset of X-ray images, showing that we are in line with the state-of-the-art automatic methods for this task.

Evaluation of algorithms for Multi-Modality Whole Heart Segmentation: An open-access grand challenge.

Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be challenging due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, an initial set of training data is generally needed for constructing priors or for training. Furthermore, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provided 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results showed that the performance of CT WHS was generally better than that of MRI WHS. The segmentation of the substructures for different categories of patients could present different levels of challenge due to the difference in imaging and variations of heart shapes. The deep learning (DL)-based methods demonstrated great potential, though several of them reported poor results in the blinded evaluation. Their performance could vary greatly across different network structures and training strategies. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated good performance, though the accuracy and computational efficiency could be limited. The challenge, including provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/).

Segmenting and tracking cell instances with cosine embeddings and recurrent hourglass networks.

Differently to semantic segmentation, instance segmentation assigns unique labels to each individual instance of the same object class. In this work, we propose a novel recurrent fully convolutional network architecture for tracking such instance segmentations over time, which is highly relevant, e.g., in biomedical applications involving cell growth and migration. Our network architecture incorporates convolutional gated recurrent units (ConvGRU) into a stacked hourglass network to utilize temporal information, e.g., from microscopy videos. Moreover, we train our network with a novel embedding loss based on cosine similarities, such that the network predicts unique embeddings for every instance throughout videos, even in the presence of dynamic structural changes due to mitosis of cells. To create the final tracked instance segmentations, the pixel-wise embeddings are clustered among subsequent video frames by using the mean shift algorithm. After showing the performance of the instance segmentation on a static in-house dataset of muscle fibers from H&E-stained microscopy images, we also evaluate our proposed recurrent stacked hourglass network regarding instance segmentation and tracking performance on six datasets from the ISBI celltracking challenge, where it delivers state-of-the-art results.

Automatic Age Estimation and Majority Age Classification From Multi-Factorial MRI Data.

Age estimation from radiologic data is an important topic both in clinical medicine as well as in forensic applications, where it is used to assess unknown chronological age or to discriminate minors from adults. In this paper, we propose an automatic multi-factorial age estimation method based on MRI data of hand, clavicle, and teeth to extend the maximal age range from up to 19 years, as commonly used for age assessment based on hand bones, to up to 25 years, when combined with clavicle bones and wisdom teeth. Fusing age-relevant information from all three anatomical sites, our method utilizes a deep convolutional neural network that is trained on a dataset of 322 subjects in the age range between 13 and 25 years, to achieve a mean absolute prediction error in regressing chronological age of 1.01±0.74 years. Furthermore, when used for majority age classification, we show that a classifier derived from thresholding our regression-based predictor is better suited than a classifier directly trained with a classification loss, especially when taking into account that those cases of minors being wrongly classified as adults need to be minimized. In conclusion, we overcome the limitations of the multi-factorial methods currently used in forensic practice, i.e., dependence on ionizing radiation, subjectivity in quantifying age-relevant information, and lack of an established approach to fuse this information from individual anatomical sites.

Integrating spatial configuration into heatmap regression based CNNs for landmark localization.

In many medical image analysis applications, only a limited amount of training data is available due to the costs of image acquisition and the large manual annotation effort required from experts. Training recent state-of-the-art machine learning methods like convolutional neural networks (CNNs) from small datasets is a challenging task. In this work on anatomical landmark localization, we propose a CNN architecture that learns to split the localization task into two simpler sub-problems, reducing the overall need for large training datasets. Our fully convolutional SpatialConfiguration-Net (SCN) learns this simplification due to multiplying the heatmap predictions of its two components and by training the network in an end-to-end manner. Thus, the SCN dedicates one component to locally accurate but ambiguous candidate predictions, while the other component improves robustness to ambiguities by incorporating the spatial configuration of landmarks. In our extensive experimental evaluation, we show that the proposed SCN outperforms related methods in terms of landmark localization error on a variety of size-limited 2D and 3D landmark localization datasets, i.e., hand radiographs, lateral cephalograms, hand MRIs, and spine CTs.

Integrating geometric configuration and appearance information into a unified framework for anatomical landmark localization.

In approaches for automatic localization of multiple anatomical landmarks, disambiguation of locally similar structures as obtained by locally accurate candidate generation is often performed by solely including high level knowledge about geometric landmark configuration. In our novel localization approach, we propose to combine both image appearance information and geometric landmark configuration into a unified random forest framework integrated into an optimization procedure that iteratively refines joint landmark predictions by using the coordinate descent algorithm. Depending on how strong multiple landmarks are correlated in a specific localization task, this integration has the benefit that it remains flexible in deciding whether appearance information or the geometric configuration of multiple landmarks is the stronger cue for solving a localization problem both accurately and robustly. Furthermore, no preliminary choice on how to encode a graphical model describing landmark configuration has to be made. In an extensive evaluation on five challenging datasets involving different 2D and 3D imaging modalities, we show that our proposed method is widely applicable and delivers state-of-the-art results when compared to various other related methods.

Evaluation and comparison of 3D intervertebral disc localization and segmentation methods for 3D T2 MR data: A grand challenge.

The evaluation of changes in Intervertebral Discs (IVDs) with 3D Magnetic Resonance (MR) Imaging (MRI) can be of interest for many clinical applications. This paper presents the evaluation of both IVD localization and IVD segmentation methods submitted to the Automatic 3D MRI IVD Localization and Segmentation challenge, held at the 2015 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI2015) with an on-site competition. With the construction of a manually annotated reference data set composed of 25 3D T2-weighted MR images acquired from two different studies and the establishment of a standard validation framework, quantitative evaluation was performed to compare the results of methods submitted to the challenge. Experimental results show that overall the best localization method achieves a mean localization distance of 0.8 mm and the best segmentation method achieves a mean Dice of 91.8%, a mean average absolute distance of 1.1 mm and a mean Hausdorff distance of 4.3 mm, respectively. The strengths and drawbacks of each method are discussed, which provides insights into the performance of different IVD localization and segmentation methods.

What automated age estimation of hand and wrist MRI data tells us about skeletal maturation in male adolescents.

BACKGROUND: Age estimation of individuals is important in human biology and has various medical and forensic applications. Recent interest in MR-based methods aims to investigate alternatives for established methods involving ionising radiation. Automatic, software-based methods additionally promise improved estimation objectivity. AIM: To investigate how informative automatically selected image features are regarding their ability to discriminate age, by exploring a recently proposed software-based age estimation method for MR images of the left hand and wrist. SUBJECTS AND METHODS: One hundred and two MR datasets of left hand images are used to evaluate age estimation performance, consisting of bone and epiphyseal gap volume localisation, computation of one age regression model per bone mapping image features to age and fusion of individual bone age predictions to a final age estimate. RESULTS: Quantitative results of the software-based method show an age estimation performance with a mean absolute difference of 0.85 years (SD = 0.58 years) to chronological age, as determined by a cross-validation experiment. Qualitatively, it is demonstrated how feature selection works and which image features of skeletal maturation are automatically chosen to model the non-linear regression function. CONCLUSION: Feasibility of automatic age estimation based on MRI data is shown and selected image features are found to be informative for describing anatomical changes during physical maturation in male adolescents.

Minimum cement volume for vertebroplasty.

PURPOSE: Percutaneous vertebroplasty is a widely used vertebral augmentation technique. It is a minimally invasive and low-risk procedure, but has some disadvantages with a relatively high number of bone cement leaks and adjacent vertebral fractures. The aim of this cadaveric study was to determine the minimum percentage of cement fill volume in vertebroplasty needed to restore vertebral stiffness and adjacent intradiscal pressure. METHODS: Thirteen thoracolumbar spine mobile segments were loaded to induce a vertebral fracture. After fracture vertebroplasty was performed, four times in the same fractured vertebra. The injected cement volume was 5 % of the fractured vertebral volume to reach 5, 10, 15 and 20 % of cement fill. Biomechanical testing was performed before the fracture, after the fracture and after each cement injection. RESULTS: After vertebral fracture compressive stiffness was reduced to 47 % of the pre-fracture value and was partially restored to 61 % after 10 % cement fill. With vertebroplasty intradiscal pressure gradually increased, depending on specimen position, from 48 to a total of 71 % at 15 % of cement fill. CONCLUSIONS: Compressive stiffness and intradiscal pressure increase with the percentage of cement fill. Fifteen per cent of cement fill was the limit beyond which no substantial increase in compressive stiffness or intradiscal pressure could be detected and is the minimum volume of cement we recommend for vertebroplasty. In the average thoracolumbar vertebra this means 4-6 ml of cement.

Towards automatic bone age estimation from MRI: localization of 3D anatomical landmarks.

Bone age estimation (BAE) is an important procedure in forensic practice which recently has seen a shift in attention from X-ray to MRI based imaging. To automate BAE from MRI, localization of the joints between hand bones is a crucial first step, which is challenging due to anatomical variations, different poses and repeating structures within the hand. We propose a landmark localization algorithm using multiple random regression forests, first analyzing the shape of the hand from information of the whole image, thus implicitly modeling the global landmark configuration, followed by a refinement based on more local information to increase prediction accuracy. We are able to clearly outperform related approaches on our dataset of 60 T1-weighted MR images, achieving a mean landmark localization error of 1.4 ± 1.5mm, while having only 0.25% outliers with an error greater than 10mm.

Fully automatic bone age estimation from left hand MR images.

There has recently been an increased demand in bone age estimation (BAE) of living individuals and human remains in legal medicine applications. A severe drawback of established BAE techniques based on X-ray images is radiation exposure, since many countries prohibit scanning involving ionizing radiation without diagnostic reasons. We propose a completely automated method for BAE based on volumetric hand MRI images. On our database of 56 male caucasian subjects between 13 and 19 years, we are able to estimate the subjects age with a mean difference of 0.85 ± 0.58 years compared to the chronological age, which is in line with radiologist results using established radiographic methods. We see this work as a promising first step towards a novel MRI based bone age estimation system, with the key benefits of lacking exposure to ionizing radiation and higher accuracy due to exploitation of volumetric data.

Parametric modelling and segmentation of vertebral bodies in 3D CT and MR spine images.

Accurate and objective evaluation of vertebral deformations is of significant importance in clinical diagnostics and therapy of pathological conditions affecting the spine. Although modern clinical practice is focused on three-dimensional (3D) computed tomography (CT) and magnetic resonance (MR) imaging techniques, the established methods for evaluation of vertebral deformations are limited to measuring deformations in two-dimensional (2D) x-ray images. In this paper, we propose a method for quantitative description of vertebral body deformations by efficient modelling and segmentation of vertebral bodies in 3D. The deformations are evaluated from the parameters of a 3D superquadric model, which is initialized as an elliptical cylinder and then gradually deformed by introducing transformations that yield a more detailed representation of the vertebral body shape. After modelling the vertebral body shape with 25 clinically meaningful parameters and the vertebral body pose with six rigid body parameters, the 3D model is aligned to the observed vertebral body in the 3D image. The performance of the method was evaluated on 75 vertebrae from CT and 75 vertebrae from T(2)-weighted MR spine images, extracted from the thoracolumbar part of normal and pathological spines. The results show that the proposed method can be used for 3D segmentation of vertebral bodies in CT and MR images, as the proposed 3D model is able to describe both normal and pathological vertebral body deformations. The method may therefore be used for initialization of whole vertebra segmentation or for quantitative measurement of vertebral body deformations.

Automated detection of spinal centrelines, vertebral bodies and intervertebral discs in CT and MR images of lumbar spine.

We propose a completely automated algorithm for the detection of the spinal centreline and the centres of vertebral bodies and intervertebral discs in images acquired by computed tomography (CT) and magnetic resonance (MR) imaging. The developed methods are based on the analysis of the geometry of spinal structures and the characteristics of CT and MR images and were evaluated on 29 CT and 13 MR images of lumbar spine. The overall mean distance between the obtained and the ground truth spinal centrelines and centres of vertebral bodies and intervertebral discs were 1.8 +/- 1.1 mm and 2.8 +/- 1.9 mm, respectively, and no considerable differences were detected among the results for CT, T(1)-weighted MR and T(2)-weighted MR images. The knowledge of the location of the spinal centreline and the centres of vertebral bodies and intervertebral discs is valuable for the analysis of the spine. The proposed method may therefore be used to initialize the techniques for labelling and segmentation of vertebrae.