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Knee Osteoarthritis (KOA) is a highly prevalent chronic musculoskeletal condition with no currently available treatment. The manifestation of KOA is heterogeneous and prediction of its progression is challenging. Current literature suggests that the use of multi-modal data and advanced modeling methods, such as the ones based on Deep Learning, has promise in tackling this challenge. To date, however, the evidence on the efficacy of this approach is limited. In this study, we leveraged recent advances in Deep Learning and, using a Transformer approach, developed a unified framework for the multi-modal fusion of knee imaging data. Subsequently, we analyzed its performance across a range of scenarios by investigating multiple progression horizons -- from short-term to long-term. We report our findings using a large cohort (n=2421-3967) derived from the Osteoarthritis Initiative dataset. We show that structural knee MRI allows identifying radiographic KOA progressors on par with multi-modal fusion approaches, achieving an area under the ROC curve (ROC AUC) of 0.70-0.76 and Average Precision (AP) of 0.15-0.54 in 2-8 year horizons. Progression within 1 year was better predicted with a multi-modal method using X-ray, structural, and compositional MR images -- ROC AUC of 0.76(0.04), AP of 0.13(0.04) -- or via clinical data. Our follow-up analysis generally shows that prediction from the imaging data is more accurate for post-traumatic subjects, and we further investigate which subject subgroups may benefit the most. The present study provides novel insights into multi-modal imaging of KOA and brings a unified data-driven framework for studying its progression in an end-to-end manner, providing new tools for the design of more efficient clinical trials. The source code of our framework and the pre-trained models are made publicly available.

In this study, we propose a novel framework that utilizes deep learning (DL) and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of seven years. This study included subjects (1832 subjects, 3276 knees) from the baseline of the MOST study. PF joint regions-of-interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end DL method was developed for predicting PFOA progression based on imaging data in a 5-fold cross-validation setting. A set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, BMI and WOMAC score, and the radiographic osteoarthritis stage of the tibiofemoral joint (KL score). Finally, we trained an ensemble model using both imaging and clinical data. Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an AUC of 0.856 and AP of 0.431; slightly outperforming the deep learning approach without attention (AUC=0.832, AP= 0.4) and the best performing reference GBM model (AUC=0.767, AP= 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP=0.447), although the clinical significance of this minor performance gain remains unknown. This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

This paper addresses the challenge of grading visual features in lumbar spine MRI using Deep Learning. Such a method is essential for the automatic quantification of structural changes in the spine, which is valuable for understanding low back pain. Multiple recent studies investigated different architecture designs, and the most recent success has been attributed to the use of transformer architectures. In this work, we argue that with a well-tuned three-stage pipeline comprising semantic segmentation, localization, and classification, convolutional networks outperform the state-of-the-art approaches. We conducted an ablation study of the existing methods in a population cohort, and report performance generalization across various subgroups. Our code is publicly available to advance research on disc degeneration and low back pain., Comment: 5 pages, under review

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at \url{https://github.com/Oulu-IMEDS/CLIMATv2}., Comment: Accepted in IEEE Transactions on Medical Imaging 2023

Accurate prediction of knee osteoarthritis (KOA) progression from structural MRI has a potential to enhance disease understanding and support clinical trials. Prior art focused on manually designed imaging biomarkers, which may not fully exploit all disease-related information present in MRI scan. In contrast, our method learns relevant representations from raw data end-to-end using Deep Learning, and uses them for progression prediction. The method employs a 2D CNN to process the data slice-wise and aggregate the extracted features using a Transformer. Evaluated on a large cohort (n=4,866), the proposed method outperforms conventional 2D and 3D CNN-based models and achieves average precision of $0.58\pm0.03$ and ROC AUC of $0.78\pm0.01$. This paper sets a baseline on end-to-end KOA progression prediction from structural MRI. Our code is publicly available at https://github.com/MIPT-Oulu/OAProgressionMR., Comment: $\copyright$ 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works

Objective is to assess the ability of texture features for detecting radiographic patellofemoral osteoarthritis (PFOA) from knee lateral view radiographs. We used lateral view knee radiographs from MOST public use datasets (n = 5507 knees). Patellar region-of-interest (ROI) was automatically detected using landmark detection tool (BoneFinder). Hand-crafted features, based on LocalBinary Patterns (LBP), were then extracted to describe the patellar texture. First, a machine learning model (Gradient Boosting Machine) was trained to detect radiographic PFOA from the LBP features. Furthermore, we used end-to-end trained deep convolutional neural networks (CNNs) directly on the texture patches for detecting the PFOA. The proposed classification models were eventually compared with more conventional reference models that use clinical assessments and participant characteristics such as age, sex, body mass index(BMI), the total WOMAC score, and tibiofemoral Kellgren-Lawrence (KL) grade. Atlas-guided visual assessment of PFOA status by expert readers provided in the MOST public use datasets was used as a classification outcome for the models. Performance of prediction models was assessed using the area under the receiver operating characteristic curve (ROC AUC), the area under the precision-recall (PR) curve-average precision (AP)-, and Brier score in the stratified 5-fold cross validation setting.Of the 5507 knees, 953 (17.3%) had PFOA. AUC and AP for the strongest reference model including age, sex, BMI, WOMAC score, and tibiofemoral KL grade to predict PFOA were 0.817 and 0.487, respectively. Textural ROI classification using CNN significantly improved the prediction performance (ROC AUC= 0.889, AP= 0.714). We present the first study that analyses patellar bone texture for diagnosing PFOA. Our results demonstrates the potential of using texture features of patella to predict PFOA.

In medical applications, deep learning methods are built to automate diagnostic tasks. However, a clinically relevant question that practitioners usually face, is how to predict the future trajectory of a disease (prognosis). Current methods for such a problem often require domain knowledge, and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many forecasting problem from multimodal data. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner, we model a prognosis prediction problem with two transformer-based components that share information between each other. The first block in this model aims to analyze the imaging data, and the second block leverages the internal representations of the first one as inputs, also fusing them with auxiliary patient data. We show the effectiveness of our method in predicting the development of structural knee osteoarthritis changes over time. Our results show that the proposed method outperforms the state-of-the-art baselines in terms of various performance metrics. In addition, we empirically show that the existence of the multi-agent transformers with depths of 2 is sufficient to achieve good performances. Our code is publicly available at \url{https://github.com/MIPT-Oulu/CLIMAT}., Comment: 10 pages

Objective: To assess the ability of imaging-based deep learning to predict radiographic patellofemoral osteoarthritis (PFOA) from knee lateral view radiographs. Design: Knee lateral view radiographs were extracted from The Multicenter Osteoarthritis Study (MOST) (n = 18,436 knees). Patellar region-of-interest (ROI) was first automatically detected, and subsequently, end-to-end deep convolutional neural networks (CNNs) were trained and validated to detect the status of patellofemoral OA. Patellar ROI was detected using deep-learning-based object detection method. Manual PFOA status assessment provided in the MOST dataset was used as a classification outcome for the CNNs. Performance of prediction models was assessed using the area under the receiver operating characteristic curve (ROC AUC) and the average precision (AP) obtained from the precision-recall (PR) curve in the stratified 5-fold cross validation setting. Results: Of the 18,436 knees, 3,425 (19%) had PFOA. AUC and AP for the reference model including age, sex, body mass index (BMI), the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and tibiofemoral Kellgren-Lawrence (KL) grade to predict PFOA were 0.806 and 0.478, respectively. The CNN model that used only image data significantly improved the prediction of PFOA status (ROC AUC= 0.958, AP= 0.862). Conclusion: We present the first machine learning based automatic PFOA detection method. Furthermore, our deep learning based model trained on patella region from knee lateral view radiographs performs better at predicting PFOA than models based on patient characteristics and clinical assessments., Comment: 24 pages, preprint, Submitted to Osteoarthritis and Cartilage

Knee osteoarthritis (OA) is very common progressive and degenerative musculoskeletal disease worldwide creates a heavy burden on patients with reduced quality of life and also on society due to financial impact. Therefore, any attempt to reduce the burden of the disease could help both patients and society. In this study, we propose a fully automated novel method, based on combination of joint shape and convolutional neural network (CNN) based bone texture features, to distinguish between the knee radiographs with and without radiographic osteoarthritis. Moreover, we report the first attempt at describing the bone texture using CNN. Knee radiographs from Osteoarthritis Initiative (OAI) and Multicenter Osteoarthritis (MOST) studies were used in the experiments. Our models were trained on 8953 knee radiographs from OAI and evaluated on 3445 knee radiographs from MOST. Our results demonstrate that fusing the proposed shape and texture parameters achieves the state-of-the art performance in radiographic OA detection yielding area under the ROC curve (AUC) of 95.21%, Comment: MIUA2020

Knee osteoarthritis (OA) is one of the highest disability factors in the world. This musculoskeletal disorder is assessed from clinical symptoms, and typically confirmed via radiographic assessment. This visual assessment done by a radiologist requires experience, and suffers from moderate to high inter-observer variability. The recent literature has shown that deep learning methods can reliably perform the OA severity assessment according to the gold standard Kellgren-Lawrence (KL) grading system. However, these methods require large amounts of labeled data, which are costly to obtain. In this study, we propose the Semixup algorithm, a semi-supervised learning (SSL) approach to leverage unlabeled data. Semixup relies on consistency regularization using in- and out-of-manifold samples, together with interpolated consistency. On an independent test set, our method significantly outperformed other state-of-the-art SSL methods in most cases. Finally, when compared to a well-tuned fully supervised baseline that yielded a balanced accuracy (BA) of $70.9\pm0.8%$ on the test set, Semixup had comparable performance -- BA of $71\pm0.8%$ $(p=0.368)$ while requiring $6$ times less labeled data. These results show that our proposed SSL method allows building fully automatic OA severity assessment tools with datasets that are available outside research settings., Comment: 11 main, 03 supplementary pages. The manuscript was accepted to IEEE Transactions on Medical Imaging in August 2020

The purposes of this study were to investigate: 1) the effect of placement of region-of-interest (ROI) for texture analysis of subchondral bone in knee radiographs, and 2) the ability of several texture descriptors to distinguish between the knees with and without radiographic osteoarthritis (OA). Bilateral posterior-anterior knee radiographs were analyzed from the baseline of OAI and MOST datasets. A fully automatic method to locate the most informative region from subchondral bone using adaptive segmentation was developed. We used an oversegmentation strategy for partitioning knee images into the compact regions that follow natural texture boundaries. LBP, Fractal Dimension (FD), Haralick features, Shannon entropy, and HOG methods were computed within the standard ROI and within the proposed adaptive ROIs. Subsequently, we built logistic regression models to identify and compare the performances of each texture descriptor and each ROI placement method using 5-fold cross validation setting. Importantly, we also investigated the generalizability of our approach by training the models on OAI and testing them on MOST dataset.We used area under the receiver operating characteristic (ROC) curve (AUC) and average precision (AP) obtained from the precision-recall (PR) curve to compare the results. We found that the adaptive ROI improves the classification performance (OA vs. non-OA) over the commonly used standard ROI (up to 9% percent increase in AUC). We also observed that, from all texture parameters, LBP yielded the best performance in all settings with the best AUC of 0.840 [0.825, 0.852] and associated AP of 0.804 [0.786, 0.820]. Compared to the current state-of-the-art approaches, our results suggest that the proposed adaptive ROI approach in texture analysis of subchondral bone can increase the diagnostic performance for detecting the presence of radiographic OA.

Degeneration of articular cartilage (AC) is actively studied in knee osteoarthritis (OA) research via magnetic resonance imaging (MRI). Segmentation of AC tissues from MRI data is an essential step in quantification of their damage. Deep learning (DL) based methods have shown potential in this realm and are the current state-of-the-art, however, their robustness to heterogeneity of MRI acquisition settings remains an open problem. In this study, we investigated two modern regularization techniques -- mixup and adversarial unsupervised domain adaptation (UDA) -- to improve the robustness of DL-based knee cartilage segmentation to new MRI acquisition settings. Our validation setup included two datasets produced by different MRI scanners and using distinct data acquisition protocols. We assessed the robustness of automatic segmentation by comparing mixup and UDA approaches to a strong baseline method at different OA severity stages and, additionally, in relation to anatomical locations. Our results showed that for moderate changes in knee MRI data acquisition settings both approaches may provide notable improvements in the robustness, which are consistent for all stages of the disease and affect the clinically important areas of the knee joint. However, mixup may be considered as a recommended approach, since it is more computationally efficient and does not require additional data from the target acquisition setup.

This paper addresses the challenge of localization of anatomical landmarks in knee X-ray images at different stages of osteoarthritis (OA). Landmark localization can be viewed as regression problem, where the landmark position is directly predicted by using the region of interest or even full-size images leading to large memory footprint, especially in case of high resolution medical images. In this work, we propose an efficient deep neural networks framework with an hourglass architecture utilizing a soft-argmax layer to directly predict normalized coordinates of the landmark points. We provide an extensive evaluation of different regularization techniques and various loss functions to understand their influence on the localization performance. Furthermore, we introduce the concept of transfer learning from low-budget annotations, and experimentally demonstrate that such approach is improving the accuracy of landmark localization. Compared to the prior methods, we validate our model on two datasets that are independent from the train data and assess the performance of the method for different stages of OA severity. The proposed approach demonstrates better generalization performance compared to the current state-of-the-art., Comment: Accepted for Publication at ICCV 2019 VRMI Workshop

Knee osteoarthritis (OA) is the most common musculoskeletal disease in the world. In primary healthcare, knee OA is diagnosed using clinical examination and radiographic assessment. Osteoarthritis Research Society International (OARSI) atlas of OA radiographic features allows to perform independent assessment of knee osteophytes, joint space narrowing and other knee features. This provides a fine-grained OA severity assessment of the knee, compared to the gold standard and most commonly used Kellgren-Lawrence (KL) composite score. However, both OARSI and KL grading systems suffer from moderate inter-rater agreement, and therefore, the use of computer-aided methods could help to improve the reliability of the process. In this study, we developed a robust, automatic method to simultaneously predict KL and OARSI grades in knee radiographs. Our method is based on Deep Learning and leverages an ensemble of deep residual networks with 50 layers, squeeze-excitation and ResNeXt blocks. Here, we used transfer learning from ImageNet with a fine-tuning on the whole Osteoarthritis Initiative (OAI) dataset. An independent testing of our model was performed on the whole Multicenter Osteoarthritis Study (MOST) dataset. Our multi-task method yielded Cohen's kappa coefficients of 0.82 for KL-grade and 0.79, 0.84, 0.94, 0.83, 0.84, 0.90 for femoral osteophytes, tibial osteophytes and joint space narrowing for lateral and medial compartments respectively. Furthermore, our method yielded area under the ROC curve of 0.98 and average precision of 0.98 for detecting the presence of radiographic OA (KL $\geq 2$), which is better than the current state-of-the-art.

Three-dimensional (3D) semi-quantitative grading of pathological features in articular cartilage (AC) offers significant improvements in basic research of osteoarthritis (OA). We have earlier developed the 3D protocol for imaging of AC and its structures which includes staining of the sample with a contrast agent (phosphotungstic acid, PTA) and a consequent scanning with micro-computed tomography. Such a protocol was designed to provide X-ray attenuation contrast to visualize AC structure. However, at the same time, this protocol has one major disadvantage: the loss of contrast at the tidemark (calcified cartilage interface, CCI). An accurate segmentation of CCI can be very important for understanding the etiology of OA and ex-vivo evaluation of tidemark condition at early OA stages. In this paper, we present the first application of Deep Learning to PTA-stained osteochondral samples that allows to perform tidemark segmentation in a fully-automatic manner. Our method is based on U-Net trained using a combination of binary cross-entropy and soft Jaccard loss. On cross-validation, this approach yielded intersection over the union of 0.59, 0.70, 0.79, 0.83 and 0.86 within 15 {\mu}m, 30 {\mu}m, 45 {\mu}m, 60 {\mu}m and 75 {\mu}m padded zones around the tidemark, respectively. Our codes and the dataset that consisted of 35 PTA-stained human AC samples are made publicly available together with the segmentation masks to facilitate the development of biomedical image segmentation methods.

Knee osteoarthritis (OA) is the most common musculoskeletal disease without a cure, and current treatment options are limited to symptomatic relief. Prediction of OA progression is a very challenging and timely issue, and it could, if resolved, accelerate the disease modifying drug development and ultimately help to prevent millions of total joint replacement surgeries performed annually. Here, we present a multi-modal machine learning-based OA progression prediction model that utilizes raw radiographic data, clinical examination results and previous medical history of the patient. We validated this approach on an independent test set of 3,918 knee images from 2,129 subjects. Our method yielded area under the ROC curve (AUC) of 0.79 (0.78-0.81) and Average Precision (AP) of 0.68 (0.66-0.70). In contrast, a reference approach, based on logistic regression, yielded AUC of 0.75 (0.74-0.77) and AP of 0.62 (0.60-0.64). The proposed method could significantly improve the subject selection process for OA drug-development trials and help the development of personalized therapeutic plans.

Plain radiography is the most common modality to assess the stage of osteoarthritis. Our aims were to assess the relationship of radiography-based bone density and texture between radiographs with minimal and clinical post-processing, and to compare the differences in bone characteristics between controls and subjects with knee osteoarthritis or medial tibial bone marrow lesions (BMLs). Tibial bone density and texture was evaluated from radiographs with both minimal and clinical post-processing in 109 subjects with and without osteoarthritis. Bone texture was evaluated using fractal signature analysis. Significant correlations (p<0.001) were found in all regions (between 0.94 and 0.97) for calibrated bone density between radiographs with minimal and clinical post-processing. Correlations varied between 0.51 and 0.97 (p<0.001) for FD_Ver texture variable and between -0.10 and 0.97 for FD_Hor. Bone density and texture were different (p<0.05) between controls and subjects with osteoarthritis or BMLs mainly in medial tibial regions. When classifying healthy and osteoarthritic subjects using a machine learning-based elastic net model with bone characteristics, area under the receiver operating characteristics (ROCAUC) curve was 0.77. For classifying controls and subjects with BMLs, ROCAUC was 0.85. In conclusion, differences in bone density and texture can be assessed from knee radiographs when using minimal post-processing.

Knee osteoarthritis (OA) is the most common musculoskeletal disorder. OA diagnosis is currently conducted by assessing symptoms and evaluating plain radiographs, but this process suffers from subjectivity. In this study, we present a new transparent computer-aided diagnosis method based on the Deep Siamese Convolutional Neural Network to automatically score knee OA severity according to the Kellgren-Lawrence grading scale. We trained our method using the data solely from the Multicenter Osteoarthritis Study and validated it on randomly selected 3,000 subjects (5,960 knees) from Osteoarthritis Initiative dataset. Our method yielded a quadratic Kappa coefficient of 0.83 and average multiclass accuracy of 66.71\% compared to the annotations given by a committee of clinical experts. Here, we also report a radiological OA diagnosis area under the ROC curve of 0.93. We also present attention maps -- given as a class probability distribution -- highlighting the radiological features affecting the network decision. This information makes the decision process transparent for the practitioner, which builds better trust toward automatic methods. We believe that our model is useful for clinical decision making and for OA research; therefore, we openly release our training codes and the data set created in this study.

X-ray tomography is a reliable tool for determining the inner structure of 3D object with penetrating X-rays. However, traditional reconstruction methods such as FDK require dense angular sampling in the data acquisition phase leading to long measurement times, especially in X-ray micro-tomography to obtain high resolution scans. Acquiring less data using greater angular steps is an obvious way for speeding up the process and avoiding the need to save huge data sets available memory. However, computing 3D reconstruction from such a sparsely sampled dataset is very sensitive to measurement noise and modelling errors. An automatic regularization method is proposed for robust reconstruction, based on enforcing sparsity in the three-dimensional shearlet transform domain. The inputs of the algorithm are the projection data and {\it a priori} known expected degree of sparsity, denoted $0<{\mathcal C}_{pr}\leq 1$. The number ${\mathcal C}_{pr}$ can be calibrated from a few dense-angle reconstructions and fixed. Human subchondral bone samples were tested and morphometric parameters of the bone reconstructions were then analyzed using standard metrics. The proposed method is shown to outperform the baseline algorithm (FDK) in the case of sparsely collected data. The number of X-ray projections can be reduced up to 10\% of the total amount while retaining the quality of the reconstruction images and of the morphometric paramaters.

Osteoarthritis (OA) is a common musculoskeletal condition typically diagnosed from radiographic assessment after clinical examination. However, a visual evaluation made by a practitioner suffers from subjectivity and is highly dependent on the experience. Computer-aided diagnostics (CAD) could improve the objectivity of knee radiographic examination. The first essential step of knee OA CAD is to automatically localize the joint area. However, according to the literature this task itself remains challenging. The aim of this study was to develop novel and computationally efficient method to tackle the issue. Here, three different datasets of knee radiographs were used (n = 473/93/77) to validate the overall performance of the method. Our pipeline consists of two parts: anatomically-based joint area proposal and their evaluation using Histogram of Oriented Gradients and the pre-trained Support Vector Machine classifier scores. The obtained results for the used datasets show the mean intersection over the union equal to: 0.84, 0.79 and 0.78. Using a high-end computer, the method allows to automatically annotate conventional knee radiographs within 14-16ms and high resolution ones within 170ms. Our results demonstrate that the developed method is suitable for large-scale analyses., Comment: Accepted to Scandinavian Conference on Image Analysis (SCIA) 2017