Deep Learning-Based Regression and Classification for Automatic Landmark Localization in Medical Images

In this study, we propose a fast and accurate method to automatically localize anatomical landmarks in medical images. We employ a global-to-local localization approach using fully convolutional neural networks (FCNNs). First, a global FCNN localizes multiple landmarks through the analysis of image patches, performing regression and classification simultaneously. In regression, displacement vectors pointing from the center of image patches towards landmark locations are determined. In classification, presence of landmarks of interest in the patch is established. Global landmark locations are obtained by averaging the predicted displacement vectors, where the contribution of each displacement vector is weighted by the posterior classification probability of the patch that it is pointing from. Subsequently, for each landmark localized with global localization, local analysis is performed. Specialized FCNNs refine the global landmark locations by analyzing local sub-images in a similar manner, i.e. by performing regression and classification simultaneously and combining the results. Evaluation was performed through localization of 8 anatomical landmarks in CCTA scans, 2 landmarks in olfactory MR scans, and 19 landmarks in cephalometric X-rays. We demonstrate that the method performs similarly to a second observer and is able to localize landmarks in a diverse set of medical images, differing in image modality, image dimensionality, and anatomical coverage.Comment: 12 pages, accepted at IEEE transactions in Medical Imagin

Stratified decision forests for accurate anatomical landmark localization in cardiac images

Accurate localization of anatomical landmarks is an important step in medical imaging, as it provides useful prior information for subsequent image analysis and acquisition methods. It is particularly useful for initialization of automatic image analysis tools (e.g. segmentation and registration) and detection of scan planes for automated image acquisition. Landmark localization has been commonly performed using learning based approaches, such as classifier and/or regressor models. However, trained models may not generalize well in heterogeneous datasets when the images contain large differences due to size, pose and shape variations of organs. To learn more data-adaptive and patient specific models, we propose a novel stratification based training model, and demonstrate its use in a decision forest. The proposed approach does not require any additional training information compared to the standard model training procedure and can be easily integrated into any decision tree framework. The proposed method is evaluated on 1080 3D highresolution and 90 multi-stack 2D cardiac cine MR images. The experiments show that the proposed method achieves state-of-theart landmark localization accuracy and outperforms standard regression and classification based approaches. Additionally, the proposed method is used in a multi-atlas segmentation to create a fully automatic segmentation pipeline, and the results show that it achieves state-of-the-art segmentation accuracy

腹部CT像上の複数オブジェクトのセグメンテーションのための統計的手法に関する研究

Computer aided diagnosis (CAD) is the use of a computer-generated output as an auxiliary tool for the assistance of efficient interpretation and accurate diagnosis. Medical image segmentation has an essential role in CAD in clinical applications. Generally, the task of medical image segmentation involves multiple objects, such as organs or diffused tumor regions. Moreover, it is very unfavorable to segment these regions from abdominal Computed Tomography (CT) images because of the overlap in intensity and variability in position and shape of soft tissues. In this thesis, a progressive segmentation framework is proposed to extract liver and tumor regions from CT images more efficiently, which includes the steps of multiple organs coarse segmentation, fine segmentation, and liver tumors segmentation. Benefit from the previous knowledge of the shape and its deformation, the Statistical shape model (SSM) method is firstly utilized to segment multiple organs regions robustly. In the process of building an SSM, the correspondence of landmarks is crucial to the quality of the model. To generate a more representative prototype of organ surface, a k-mean clustering method is proposed. The quality of the SSMs, which is measured by generalization ability, specificity, and compactness, was improved. We furtherly extend the shapes correspondence to multiple objects. A non-rigid iterative closest point surface registration process is proposed to seek more properly corresponded landmarks across the multi-organ surfaces. The accuracy of surface registration was improved as well as the model quality. Moreover, to localize the abdominal organs simultaneously, we proposed a random forest regressor cooperating intensity features to predict the position of multiple organs in the CT image. The regions of the organs are substantially restrained using the trained shape models. The accuracy of coarse segmentation using SSMs was increased by the initial information of organ positions.Consequently, a pixel-wise segmentation using the classification of supervoxels is applied for the fine segmentation of multiple organs. The intensity and spatial features are extracted from each supervoxels and classified by a trained random forest. The boundary of the supervoxels is closer to the real organs than the previous coarse segmentation. Finally, we developed a hybrid framework for liver tumor segmentation in multiphase images. To deal with these issues of distinguishing and delineating tumor regions and peripheral tissues, this task is accomplished in two steps: a cascade region-based convolutional neural network (R-CNN) with a refined head is trained to locate the bounding boxes that contain tumors, and a phase-sensitive noise filtering is introduced to refine the following segmentation of tumor regions conducted by a level-set-based framework. The results of tumor detection show the adjacent tumors are successfully separated by the improved cascaded R-CNN. The accuracy of tumor segmentation is also improved by our proposed method. 26 cases of multi-phase CT images were used to validate our proposed method for the segmentation of liver tumors. The average precision and recall rates for tumor detection are 76.8% and 84.4%, respectively. The intersection over union, true positive rate, and false positive rate for tumor segmentation are 72.7%, 76.2%, and 4.75%, respectively.九州工業大学博士学位論文 学位記番号: 工博甲第546号 学位授与年月日: 令和4年3月25日1 Introduction|2 Literature Review|3 Statistical Shape Model Building|4 Multi-organ Segmentation|5 Liver Tumors Segmentation|6 Summary and Outlook九州工業大学令和3年

Label Efficient Deep Learning in Medical Imaging

Recent state-of-the-art deep learning frameworks require large, fully annotated training datasets that are, depending on the objective, time-consuming to generate. While in most fields, these labelling tasks can be parallelized massively or even outsourced, this is not the case for medical images. Usually, only a highly trained expert is able to generate these datasets. However, since additional manual annotation, especially for the purpose of segmentation or tracking, is typically not part of a radiologist's workflow, large and fully annotated datasets are a rare and scarce good. In this context, a variety of frameworks are proposed in this work to solve the problems that arise due to the lack of annotated training data across different medical imaging tasks and modalities. The first contribution as part of this thesis was to investigate weakly supervised learning on PET/CT data for the task of lesion segmentation. Using only class labels (tumor vs. no tumor), a classifier was first trained and subsequently used to generate Class Activation Maps highlighting regions with lesions. Based on these region proposals, final tumor segmentation could be performed with high accuracy in clinically relevant metrics. This drastically simplifies the process of training data generation, as only class labels have to be assigned to each slice of a scan instead of a full pixel-wise segmentation. To further reduce the time required to prepare training data, two self-supervised methods were investigated for the task of anatomical tissue segmentation and landmark detection. To this end, as a second contribution, a state-of-the-art tracking framework based on contrastive random walks was transferred, adapted and extended to the medical imaging domain. As contrastive learning often lacks real-time capability, a self-supervised template matching network was developed to address the task of real-time anatomical tissue tracking, yielding the third contribution of this work. Both of these methods have in common that only during inference the object or region of interest is defined, reducing the number of required labels to as few as one and allowing adaptation to different tasks without having to re-train or access the original training data. Despite the limited amount of labelled data, good results could be achieved for both tracking of organs across subjects as well as tissue tracking within time-series. State-of-the-art self-supervised learning in medical imaging is usually performed on 2D slices due to the lack of training data and limited computational resources. To exploit the three-dimensional structure of this type of data, self-supervised contrastive learning was performed on entire volumes using over 40,000 whole-body MRI scans forming the fourth contribution. Due to this pre-training, a large number of downstream tasks could be successfully addressed using only limited labelled data. Furthermore, the learned representations allows to visualize the entire dataset in a two-dimensional view. To encourage research in the field of automated lesion segmentation in PET/CT image data, the autoPET challenge was organized, which represents the fifth contribution

3D shape instantiation for intra-operative navigation from a single 2D projection

Unlike traditional open surgery where surgeons can see the operation area clearly, in robot-assisted Minimally Invasive Surgery (MIS), a surgeon’s view of the region of interest is usually limited. Currently, 2D images from fluoroscopy, Magnetic Resonance Imaging (MRI), endoscopy or ultrasound are used for intra-operative guidance as real-time 3D volumetric acquisition is not always possible due to the acquisition speed or exposure constraints. 3D reconstruction, however, is key to navigation in complex in vivo geometries and can help resolve this issue. Novel 3D shape instantiation schemes are developed in this thesis, which can reconstruct the high-resolution 3D shape of a target from limited 2D views, especially a single 2D projection or slice. To achieve a complete and automatic 3D shape instantiation pipeline, segmentation schemes based on deep learning are also investigated. These include normalization schemes for training U-Nets and network architecture design of Atrous Convolutional Neural Networks (ACNNs). For U-Net normalization, four popular normalization methods are reviewed, then Instance-Layer Normalization (ILN) is proposed. It uses a sigmoid function to linearly weight the feature map after instance normalization and layer normalization, and cascades group normalization after the weighted feature map. Detailed validation results potentially demonstrate the practical advantages of the proposed ILN for effective and robust segmentation of different anatomies. For network architecture design in training Deep Convolutional Neural Networks (DCNNs), the newly proposed ACNN is compared to traditional U-Net where max-pooling and deconvolutional layers are essential. Only convolutional layers are used in the proposed ACNN with different atrous rates and it has been shown that the method is able to provide a fully-covered receptive field with a minimum number of atrous convolutional layers. ACNN enhances the robustness and generalizability of the analysis scheme by cascading multiple atrous blocks. Validation results have shown the proposed method achieves comparable results to the U-Net in terms of medical image segmentation, whilst reducing the trainable parameters, thus improving the convergence and real-time instantiation speed. For 3D shape instantiation of soft and deforming organs during MIS, Sparse Principle Component Analysis (SPCA) has been used to analyse a 3D Statistical Shape Model (SSM) and to determine the most informative scan plane. Synchronized 2D images are then scanned at the most informative scan plane and are expressed in a 2D SSM. Kernel Partial Least Square Regression (KPLSR) has been applied to learn the relationship between the 2D and 3D SSM. It has been shown that the KPLSR-learned model developed in this thesis is able to predict the intra-operative 3D target shape from a single 2D projection or slice, thus permitting real-time 3D navigation. Validation results have shown the intrinsic accuracy achieved and the potential clinical value of the technique. The proposed 3D shape instantiation scheme is further applied to intra-operative stent graft deployment for the robot-assisted treatment of aortic aneurysms. Mathematical modelling is first used to simulate the stent graft characteristics. This is then followed by the Robust Perspective-n-Point (RPnP) method to instantiate the 3D pose of fiducial markers of the graft. Here, Equally-weighted Focal U-Net is proposed with a cross-entropy and an additional focal loss function. Detailed validation has been performed on patient-specific stent grafts with an accuracy between 1-3mm. Finally, the relative merits and potential pitfalls of all the methods developed in this thesis are discussed, followed by potential future research directions and additional challenges that need to be tackled.Open Acces

Liver segmentation using 3D CT scans.

Master of Science in Computer Science. University of KwaZulu-Natal, Durban, 2018.Abstract available in PDF file

3D-3D Deformable Registration and Deep Learning Segmentation based Neck Diseases Analysis in MRI

Whiplash, cervical dystonia (CD), neck pain and work-related upper limb disorder (WRULD) are the most common diseases in the cervical region. Headaches, stiffness, sensory disturbance to the legs and arms, optical problems, aching in the back and shoulder, and auditory and visual problems are common symptoms seen in patients with these diseases. CD patients may also suffer tormenting spasticity in some neck muscles, with the symptoms possibly being acute and persisting for a long time, sometimes a lifetime. Whiplash-associated disorders (WADs) may occur due to sudden forward and backward movements of the head and neck occurring during a sporting activity or vehicle or domestic accident. These diseases affect private industries, insurance companies and governments, with the socio-economic costs significantly related to work absences, long-term sick leave, early disability and disability support pensions, health care expenses, reduced productivity and insurance claims. Therefore, diagnosing and treating neck-related diseases are important issues in clinical practice. The reason for these afflictions resulting from accident is the impairment of the cervical muscles which undergo atrophy or pseudo-hypertrophy due to fat infiltrating into them. These morphological changes have to be determined by identifying and quantifying their bio-markers before applying any medical intervention. Volumetric studies of neck muscles are reliable indicators of the proper treatments to apply. Radiation therapy, chemotherapy, injection of a toxin or surgery could be possible ways of treating these diseases. However, the dosages required should be precise because the neck region contains some sensitive organs, such as nerves, blood vessels and the trachea and spinal cord. Image registration and deep learning-based segmentation can help to determine appropriate treatments by analyzing the neck muscles. However, this is a challenging task for medical images due to complexities such as many muscles crossing multiple joints and attaching to many bones. Also, their shapes and sizes vary greatly across populations whereas their cross-sectional areas (CSAs) do not change in proportion to the heights and weights of individuals, with their sizes varying more significantly between males and females than ages. Therefore, the neck's anatomical variabilities are much greater than those of other parts of the human body. Some other challenges which make analyzing neck muscles very difficult are their compactness, similar gray-level appearances, intra-muscular fat, sliding due to cardiac and respiratory motions, false boundaries created by intramuscular fat, low resolution and contrast in medical images, noise, inhomogeneity and background clutter with the same composition and intensity. Furthermore, a patient's mode, position and neck movements during the capture of an image create variability. However, very little significant research work has been conducted on analyzing neck muscles. Although previous image registration efforts form a strong basis for many medical applications, none can satisfy the requirements of all of them because of the challenges associated with their implementation and low accuracy which could be due to anatomical complexities and variabilities or the artefacts of imaging devices. In existing methods, multi-resolution- and heuristic-based methods are popular. However, the above issues cause conventional multi-resolution-based registration methods to be trapped in local minima due to their low degrees of freedom in their geometrical transforms. Although heuristic-based methods are good at handling large mismatches, they require pre-segmentation and are computationally expensive. Also, current deformable methods often face statistical instability problems and many local optima when dealing with small mismatches. On the other hand, deep learning-based methods have achieved significant success over the last few years. Although a deeper network can learn more complex features and yields better performances, its depth cannot be increased as this would cause the gradient to vanish during training and result in training difficulties. Recently, researchers have focused on attention mechanisms for deep learning but current attention models face a challenge in the case of an application with compact and similar small multiple classes, large variability, low contrast and noise. The focus of this dissertation is on the design of 3D-3D image registration approaches as well as deep learning-based semantic segmentation methods for analyzing neck muscles. In the first part of this thesis, a novel object-constrained hierarchical registration framework for aligning inter-subject neck muscles is proposed. Firstly, to handle large-scale local minima, it uses a coarse registration technique which optimizes a new edge position difference (EPD) similarity measure to align large mismatches. Also, a new transformation based on the discrete periodic spline wavelet (DPSW), affine and free-form-deformation (FFD) transformations are exploited. Secondly, to avoid the monotonous nature of using transformations in multiple stages, affine registration technique, which uses a double-pushing system by changing the edges in the EPD and switching the transformation's resolutions, is designed to align small mismatches. The EPD helps in both the coarse and fine techniques to implement object-constrained registration via controlling edges which is not possible using traditional similarity measures. Experiments are performed on clinical 3D magnetic resonance imaging (MRI) scans of the neck, with the results showing that the EPD is more effective than the mutual information (MI) and the sum of squared difference (SSD) measures in terms of the volumetric dice similarity coefficient (DSC). Also, the proposed method is compared with two state-of-the-art approaches with ablation studies of inter-subject deformable registration and achieves better accuracy, robustness and consistency. However, as this method is computationally complex and has a problem handling large-scale anatomical variabilities, another 3D-3D registration framework with two novel contributions is proposed in the second part of this thesis. Firstly, a two-stage heuristic search optimization technique for handling large mismatches,which uses a minimal user hypothesis regarding these mismatches and is computationally fast, is introduced. It brings a moving image hierarchically closer to a fixed one using MI and EPD similarity measures in the coarse and fine stages, respectively, while the images do not require pre-segmentation as is necessary in traditional heuristic optimization-based techniques. Secondly, a region of interest (ROI) EPD-based registration framework for handling small mismatches using salient anatomical information (AI), in which a convex objective function is formed through a unique shape created from the desired objects in the ROI, is proposed. It is compared with two state-of-the-art methods on a neck dataset, with the results showing that it is superior in terms of accuracy and is computationally fast. In the last part of this thesis, an evaluation study of recent U-Net-based convolutional neural networks (CNNs) is performed on a neck dataset. It comprises 6 recent models, the U-Net, U-Net with a conditional random field (CRF-Unet), attention U-Net (A-Unet), nested U-Net or U-Net++, multi-feature pyramid (MFP)-Unet and recurrent residual U-Net (R2Unet) and 4 with more comprehensive modifications, the multi-scale U-Net (MS-Unet), parallel multi-scale U-Net (PMSUnet), recurrent residual attention U-Net (R2A-Unet) and R2A-Unet++ in neck muscles segmentation, with analyses of the numerical results indicating that the R2Unet architecture achieves the best accuracy. Also, two deep learning-based semantic segmentation approaches are proposed. In the first, a new two-stage U-Net++ (TS-UNet++) uses two different types of deep CNNs (DCNNs) rather than one similar to the traditional multi-stage method, with the U-Net++ in the first stage and the U-Net in the second. More convolutional blocks are added after the input and before the output layers of the multi-stage approach to better extract the low- and high-level features. A new concatenation-based fusion structure, which is incorporated in the architecture to allow deep supervision, helps to increase the depth of the network without accelerating the gradient-vanishing problem. Then, more convolutional layers are added after each concatenation of the fusion structure to extract more representative features. The proposed network is compared with the U-Net, U-Net++ and two-stage U-Net (TS-UNet) on the neck dataset, with the results indicating that it outperforms the others. In the second approach, an explicit attention method, in which the attention is performed through a ROI evolved from ground truth via dilation, is proposed. It does not require any additional CNN, as does a cascaded approach, to localize the ROI. Attention in a CNN is sensitive with respect to the area of the ROI. This dilated ROI is more capable of capturing relevant regions and suppressing irrelevant ones than a bounding box and region-level coarse annotation, and is used during training of any CNN. Coarse annotation, which does not require any detailed pixel wise delineation that can be performed by any novice person, is used during testing. This proposed ROI-based attention method, which can handle compact and similar small multiple classes with objects with large variabilities, is compared with the automatic A-Unet and U-Net, and performs best

DAD-3DHeads: A Large-scale Dense, Accurate and Diverse Dataset for 3D Head Alignment from a Single Image

We present DAD-3DHeads, a dense and diverse large-scale dataset, and a robust model for 3D Dense Head Alignment in the wild. It contains annotations of over 3.5K landmarks that accurately represent 3D head shape compared to the ground-truth scans. The data-driven model, DAD-3DNet, trained on our dataset, learns shape, expression, and pose parameters, and performs 3D reconstruction of a FLAME mesh. The model also incorporates a landmark prediction branch to take advantage of rich supervision and co-training of multiple related tasks. Experimentally, DAD-3DNet outperforms or is comparable to the state-of-the-art models in (i) 3D Head Pose Estimation on AFLW2000-3D and BIWI, (ii) 3D Face Shape Reconstruction on NoW and Feng, and (iii) 3D Dense Head Alignment and 3D Landmarks Estimation on DAD-3DHeads dataset. Finally, the diversity of DAD-3DHeads in camera angles, facial expressions, and occlusions enables a benchmark to study in-the-wild generalization and robustness to distribution shifts. The dataset webpage is https://p.farm/research/dad-3dheads