A Machine Learning and Computer Assisted Methodology for Diagnosing Chronic Lower Back Pain on Lumbar Spine Magnetic Resonance Images

Chronic Lower Back Pain (CLBP) is one of the major types of pain that affects many people around the world. It is estimated that 28.1% of US adults suffer from this illness and 2.5 million of the UK population experience this type of pain every day. Most CLBP cases do not happen overnight and it is usually developed from a less serious but acute variant of lower back pain. An acute type of lower back pain can develop into a chronic one if the underlying cause is serious and left untreated. The longer a person is disabled by back pain, the less chance he or she returns to work and the more health care cost he or she will require. It is therefore important to identify the cause of back pains as early as possible in order to improve the chance of patient rehabilitation. The speediness of early diagnosis can depend on many factors including referral time from a general practitioner to the hospital, waiting time for a specialist appointment, time for a Magnetic Resonance Imaging (MRI) scan and time for the analysis result to come out. Currently diagnosing the lower back pain is done by visual observation and analysis of the lumbar spine MRI images by radiologists and clinicians and this process could take up much of their time and effort. This, therefore, rationalizes the need for a new method to increase the efficiency and effectiveness of the imaging diagnostic process. This thesis details a novel methodology to automatically aid clinicians in performing diagnosis of CLBP on lumbar spine MRI images. The methodology is based on the current accepted medical practice of manual inspection of the MRI scans of the patient’s lumbar spine as advised by several practitioners in this field. The main methodology is divided into three sub-methods the first sub-method is disc herniation detection using disc segmentation and centroid distance function. While the second sub-method is lumbar spinal stenosis detection via segmentation of area between anterior and posterior (AAP) Elements. Whereas, the last sub-method is the use of deep learning to perform semantic segmentation to identify regions in the MRI images that are relevant to the diagnosis process. The method then performs boundary delineation between these regions, identifies key points along the boundaries and measures distances between these points that can be used as an indication to the health of the lumbar spine. Due to a limitation in the size and suitability of the currently existing open-access lumbar spine dataset necessary to train and test any good classification algorithms, a dataset consisting of 48,345 MRI slices from a complete clinical lumbar MRI study of 515 symptomatic back pain patients from several specialty hospitals around the world has been created. Each MRI study is annotated by expert radiologists with notes regarding the observed characteristics, condition of the lumbar spine, or presence of diseases. The ground-truth dataset containing manually labelled segmented images has also been developed. To complement this ground-truth dataset, a novel method of constructing and evaluating the suitability of ground truth data for lumbar spine MRI image segmentation has been developed. A subset of the dataset, which includes the data for 101 patients, is used in a set of experiments that have been conducted using a variety of algorithms to conclude with using SegNet as the image segmentation algorithm. The network consists of VGG16 layers pre-trained using a subset of non-medical images from the ImageNet database and fine-tuned using the training portion of the ground-truth dataset. The results of these experiments show the accurate delineation of important boundaries of regions in lumbar spine MRI. The experiments also show very close agreement between the expert radiologists’ notes on the condition of a lumbar spine and the conclusion of the system about the lumbar spine in the majority of cases

Multi-Surface Simplex Spine Segmentation for Spine Surgery Simulation and Planning

This research proposes to develop a knowledge-based multi-surface simplex deformable model for segmentation of healthy as well as pathological lumbar spine data. It aims to provide a more accurate and robust segmentation scheme for identification of intervertebral disc pathologies to assist with spine surgery planning. A robust technique that combines multi-surface and shape statistics-aware variants of the deformable simplex model is presented. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user-assistance is allowed to disable the prior shape influence during deformation. Results have been validated against user-assisted expert segmentation

Deformable Multisurface Segmentation of the Spine for Orthopedic Surgery Planning and Simulation

Purpose: We describe a shape-aware multisurface simplex deformable model for the segmentation of healthy as well as pathological lumbar spine in medical image data. Approach: This model provides an accurate and robust segmentation scheme for the identification of intervertebral disc pathologies to enable the minimally supervised planning and patient-specific simulation of spine surgery, in a manner that combines multisurface and shape statistics-based variants of the deformable simplex model. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user assistance is allowed to disable the prior shape influence during deformation. Results: Results demonstrate validation against user-assisted expert segmentation, showing excellent boundary agreement and prevention of spatial overlap between neighboring surfaces. This section also plots the characteristics of the statistical shape model, such as compactness, generalizability and specificity, as a function of the number of modes used to represent the family of shapes. Final results demonstrate a proof-of-concept deformation application based on the open-source surgery simulation Simulation Open Framework Architecture toolkit. Conclusions: To summarize, we present a deformable multisurface model that embeds a shape statistics force, with applications to surgery planning and simulation

A semiautomatic method to identify vertebral end plate lesions (Schmorl's nodes)

Background Context There are differences in definitions of end plate lesions (EPLs), often referred to as Schmorl’s nodes, that may, to some extent, account for the large range of reported prevalence (3.8 to 76%). Purpose To develop a technique to measure the size, prevalence and location of EPLs in a consistent manner. Study Design/Setting This study proposed a method using a detection algorithm which was applied to five adolescent females (average age 15.1 years, range 13.0 to 19.2 years) with idiopathic scoliosis (average major Cobb angle 60°, range 55 to 67°). Methods Existing low-dose, computed tomography scans were segmented semi-automatically to extract 3D morphology of each vertebral endplate. Any remaining attachments to the posterior elements of adjacent vertebrae or endplates were then manually sectioned. An automatic algorithm was used to determine the presence and position of EPLs. Results EPLs were identified in 15 of the 170 (8.8%) endplates analysed with an average depth of 3.1mm. 11/15 of the EPLs were seen in the lumbar spine. The algorithm was found to be most sensitive to changes in the minimum EPL gradient at the edges of the EPL. Conclusions This study describes an imaging analysis technique for consistent measurement of the prevalence, location and size of EPLs. The technique can be used to analyse large populations without observer errors in EPL definitions

Intervertebral Disc Structure and Mechanical Function Under Physiological Loading Quantified Non-invasively Utilizing MRI and Image Registration

The intervertebral discs (IVD) functions to permit motion, distribute load, and dissipate energy in the spine. It performs these functions through its heterogeneous structural organization and biochemical composition consisting of several tissue substructures: the central gelatinous nucleus pulposus (NP), the surrounding fiber reinforced layered annulus fibrosus (AF), and the cartilaginous endplates (CEP) that are positioned between the NP and vertebral endplates. Each tissue contributes individually to overall disc mechanics and by interacting with adjacent tissues. Disruption of the disc\u27s tissues through aging, degeneration, or tear will not only alter the affected tissue mechanical properties, but also the mechanical behavior of adjacent tissues and, ultimately, overall disc segment function. Thus, there is a need to measure disc tissue and segment mechanics in the intact disc so that interactions between substructures are not disrupted. Such measurements would be valuable to study mechanisms of disc function and degeneration, and develop and evaluate surgical procedures and therapeutic implants. The objectives of this study were to develop, validate, and apply methods to visualize and quantify IVD substructure geometry and track internal deformations for intact human discs under axial compression. The CEP and AF were visualized through MRI parameter mapping and image sequence optimization for ideal contrast. High-resolution images enabled geometric measurements. Axial compression was performed using a custom-built loading device that permitted long relaxation times outside of the MRI, 300 m isotropic resolution images were acquired, and image registration methods applied to measure 3D internal strain. In conclusion, new methods to visualize and quantify CEP thickness, annular tear detection and geometric quantification, and non-invasively measure 3D internal disc strains were established. No correlation was found between CEP thickness and disc level; however the periphery was significantly thicker compared to central locations. Clear distinction of adjacent AF lamellae enabled annular tear detection and detailed geometric quantification. Annular tears demonstrated non-classic geometry through interconnecting radial, circumferential, and perinuclear formations. Regional strain inhomogeneity was observed qualitatively and quantitatively. Variation in strain magnitudes might be explained by geometry in axial and circumferential strain while peak radial strain in the posterior AF may have important implications for disc herniation

Quantitative MRI to Characterize the Nucleus Pulposus Morphological and Biomechanical Variation According to Sagittal Bending Load and Radial Fissure, an ex vivo Ovine Specimen Proof-of-Concept Study

Background and context: Low back pain is a dramatic burden worldwide. Discography studies have shown that 39% of chronic low back pain patients suffer from discogenic pain due to a radial fissure of intervertebral disc. This can have major implications in clinical therapeutic choices. The use of discography is restricted because of its invasiveness and interest in it remains low as it represents a static condition of the disc morphology. Magnetic Resonance Imaging (MRI) appears to be less invasive but does not describe the biomechanical dynamic behavior of the fissure.Purpose: We aimed to seek a quantitative MRI protocol combined with ex vivo sagittal loading to analyze the morphological and biomechanical changes of the intervertebral disc structure and stress distribution.Study design: Proof of concept.Methods: We designed a proof-of-concept ovine study including 3 different 3.0 T-MRI sequences (T2-weighted, T1 and T2 mapping). We analyzed 3 different mechanical states (neutral, flexion and extension) on a fresh ovine spine specimen to characterize an intervertebral disc before and after puncturing the anterior part of the annulus fibrosus. We used a mark tracking method to calculate the bending angles and the axial displacements of the discal structures. In parallel, we created a finite element model to calculate the variation of the axial stress and the maximal intensity shear stress, extrapolated from our experimental boundary conditions.Results: Thanks to an original combination of specific nuclear relaxation time quantifications (T1, T2) of the discal tissue, we characterized the nucleus movement/deformation into the fissure according to the synchronous mechanical load. This revealed a link between disc abnormality and spine segment range of motion capability. Our finite element model highlighted significant variations within the stress distribution between intact and damaged disc.Conclusion: Quantitative MRI appears to provide a new opportunity to characterize intra-discal structural morphology, lesions and stress changes under the influence of mechanical load. This preliminary work could have substantial implications for non-invasive disc exploration and could help to validate novel therapies for disc treatment

The safety and efficacy of mesenchymal stem cells for prevention or regeneration of intervertebral disc degeneration: a systematic review

General Posters: abstract no. GP86INTRODUCTION: Mesenchymal stem cells (MSCs) have been used to halt the progression or regenerate the disc with hopes to prevent or treat discogenic back pain. However, the safety and efficacy of the use of MSCs for such treatment in animal and human models at short and long term assessment (i.e. greater than 48 weeks) have not been systematically addressed. This study addressed a systematic review of comparative controlled studies addressing the use of MSCs to that of no treatment/saline for the treatment of disc degeneration. METHODS: Online databases were extensively searched. Controlled trials in animal models and humans were eligible for inclusion. Trial design, MSC characteristics, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was assessed addressing trial design. Two individuals independently addressed the aforementioned. RESULTS: Twenty-two animal studies were included. No human comparative controlled trials were reported. All three types of MSCs (i.e. derived from bone marrow, synovial and adipose tissue) showed successful inhibition of disc degeneration progression. From three included studies, bone marrow derived MSC showed superior quality of disc repair when compared to other treatments, including TGF-β1, NP bilaminar co-culture and axial distraction regimen. However, osteophyte development was reported in two studies as potential complication of MSC transplantation. CONCLUSIONS: Based on animal models, the current evidence suggests that in the short-term MSC transplantation is safe and effective in halting disc degeneration; however, additional and larger studies are needed to assess the long-term regenerative effects and potential complications. Inconsistency in methodological design and outcome parameters prevent any robust conclusions. In addition, randomized controlled trials in humans are needed to assess the safety and efficacy of such therapy.published_or_final_versio

Intervertebral Disc Height Loss and Restoration: Outcomes and Implications

This thesis is unified around the theme of disc height loss. Current knowledge in the area of spine research identifies mechanical overload as the culprit for the initiation of injury to the spine. While genetic predispositions may play a factor in the severity of spine degeneration or in the resiliency to applied load, ultimately, injury occurs when a load exceeds a tissue’s tolerance. Disc height loss has the potential to be a primary factor in the progression of spinal degeneration. For example, disc height has been touted as a major component for the initiation of pathological and degenerative changes to the spine. Pathologic, non-recoverable disc height loss can occur through herniation or endplate fracture and could result in a degenerative cascade of injury that eventually involves the facet joints, narrows nerve root space, and increases stress at adjacent segments. What is not known is the degree to which disc height affects the degenerative cascade; that is, there is no quantitative data outlining the progression of mechanical consequences at adjacent segments or at the injured segment itself during disc height loss. Further, the degree to which restoring disc height, if even possible, will reverse the process of degeneration is not entirely clear. There is data which suggests that nucleus replacement can restore stress distributions within an injured disc, but the extent of repair material survivability is unknown. Finally, clinical categories of measuring spinal degeneration are based on visual cues and features from medical imaging. Understanding the links between joint visual cues and aberrant movement may help to guide clinical practice; researchers will gain greater insight into the mechanical consequences of anatomical features associated with degeneration. This thesis was comprised of three studies. Study 1 examined the effect of disc height loss and subsequent restoration using an injectable hydrogel on the relative kinematics of a segment with height loss and an adjacent segment. It was found that disc height loss produced an immediate effect, where relative angular displacement was reduced in the segment with height loss and increased in the adjacent segment. Restoring disc height with an injectable hydrogel brought the relative angular displacement of both segments back to their initial values. This study is the first of its kind to examine the immediate effects of disc height loss via loss of nucleus pulposus and restoration. Whether these effects are as clear in-vivo remains to be seen. Study 2 evaluated the efficacy of a novel repair strategy to restore the mechanical profile of a spine segment with disc height loss initiated via compressive fracture. The strategy employed the use of PMMA injected into the vertebral body to attempt to seal a fracture from above the disc, and an injectable hydrogel to restore disc height. The use of PMMA was found to restore the compressive stiffness of the injured segment to within approximately 20% of its initial value, while the use of the injectable hydrogel restored the sagittal plane rotational stiffness to within approximately 50-80% of its initial value. After further repetitive compression had been applied to the spine segment however, the restorative influence of both interventions was lost in terms of rotational and compressive stiffness. It was found that large cracks in the endplate prevented the hydrogel from being contained and quickly returned the segment back to its injured profile. Future efforts at restoring the disc while maintaining its anatomical structures need better methods of creating a sufficient seal inside the disc to allow it to re-pressurize and sustain the stresses encountered on a daily basis. Study 3 employed the use of a novel spine tracking algorithm developed as part of this thesis to evaluate sagittal plane cervical spine motion of a series of patient image sequences who had experienced trauma and had a chief complaint related to their neck, head, or shoulders. Some patients had evidence of disc height loss while others did not. Clinical subgroups were created that classified disc height loss as either moderate/severe (3 cases), mild (8 cases), or non-existent (9 cases). When normalized angular displacement of the C5/C6 segment in a group with moderate to severe height loss was compared to the same level in a group with no height loss, there was a statistically significant difference in angular displacement between the two groups (p = 0.004). Angular displacement at C5/C6 was 20.2% ± 2.3% of total measured neck angular displacement in the moderate/severe height loss group compared to 30.6% ± 4.0% of total measured neck angular displacement in the group without height loss. Based on the limited sample size of this study it would appear that disc height loss creates a loss in range of motion. This work has further revealed the heterogeneous nature of individual segmental movement patterns. However, in the group without height loss, there was a systematic trend seen of an increasing angular displacement with descending segmental level. This was not observed in those with moderate to severe disc height loss. The broad implications of this work are that disc height loss influences spine kinematics, which has implications with respect to further injury propagation through the spinal linkage. Angular displacement of a spine segment appears to be governed by its local stiffness. Restoration of disc height under real injury scenarios is a difficult proposition and any attempts at repair need to sufficiently seal the disc space and prevent extrusion of nucleus pulposus or hydrogel-based implants. We now appreciate the difficulty in this objective. Further, repeating the mechanism of injury will reduce the mechanical effects of the restorative intervention, preventing this is highly important

Automatic Segmentation of the Lumbar Spine from Medical Images

Segmentation of the lumbar spine in 3D is a necessary step in numerous medical applications, but remains a challenging problem for computational methods due to the complex and varied shape of the anatomy and the noise and other artefacts often present in the images. While manual annotation of anatomical objects such as vertebrae is often carried out with the aid of specialised software, obtaining even a single example can be extremely time-consuming. Automating the segmentation process is the only feasible way to obtain accurate and reliable segmentations on any large scale. This thesis describes an approach for automatic segmentation of the lumbar spine from medical images; specifically those acquired using magnetic resonance imaging (MRI) and computed tomography (CT). The segmentation problem is formulated as one of assigning class labels to local clustered regions of an image (called superpixels in 2D or supervoxels in 3D). Features are introduced in 2D and 3D which can be used to train a classifier for estimating the class labels of the superpixels or supervoxels. Spatial context is introduced by incorporating the class estimates into a conditional random field along with a learned pairwise metric. Inference over the resulting model can be carried out very efficiently, enabling an accurate pixel- or voxel-level segmentation to be recovered from the labelled regions. In contrast to most previous work in the literature, the approach does not rely on explicit prior shape information. It therefore avoids many of the problems associated with these methods, such as the need to construct a representative prior model of anatomical shape from training data and the approximate nature of the optimisation. The general-purpose nature of the proposed method means that it can be used to accurately segment both vertebrae and intervertebral discs from medical images without fundamental change to the model. Evaluation of the approach shows it to obtain accurate and robust performance in the presence of significant anatomical variation. The median average symmetric surface distances for 2D vertebra segmentation were 0.27mm on MRI data and 0.02mm on CT data. For 3D vertebra segmentation the median surface distances were 0.90mm on MRI data and 0.20mm on CT data. For 3D intervertebral disc segmentation a median surface distance of 0.54mm was obtained on MRI data

The effect of position on the lumbar intervertebral disc.

This thesis comprises three phases with a combined aim which was to investigate the effect of position on the lumbar intervertebral disc (IVD). The effect of position on the lumbar IVD in asymptomatic subjects and subjects with discogenic low back pain (DLBP) was explored using positional Magnetic Resonance Imaging (pMRI). Convenience samples of 11 asymptomatic and 34 DLBP subjects were recruited to have sagittal and axial pMRI scans performed in sitting (Neutral, Flexed and Extended), standing and lying (Supine and Prone extension) positions. The sagittal plane migration of the nucleus pulposus (NP) of each lumbar IVD in each position was measured from the sagittal and axial pMRI scans. Within and between group inferential analysis was performed using nonparametric tests. Both the asymptomatic and DLBP subjects demonstrated that position had statistically significant effects on the sagittal plane NP migration. Both groups demonstrated significantly greater posterior sagittal plane NP migration in Neutral and Flexed sitting positions compared to the other positions. However, between group comparisons identified that the asymptomatic subjects also demonstrated significantly greater posterior sagittal plane NP migration than the DLBP subjects. This pattern was more common in the upper lumbar IVDs (L1/2 and L2/3) between positions and less common in the lower IVDs (L4/5 and L5/S1) between positions. New knowledge regarding the behaviour of the lumbar IVD emerged from this research. The differences detected between the asymptomatic and DLBP subjects suggest that some current theories regarding DLBP may be incorrect. The results also support imaging of DLBP subjects in sitting positions as opposed to current supine positions. Although the limitations of the study reduce generalisation of the results, the implications for clinical practice, imaging and suggestions for further research from this work are important to improve understanding and conservative management of DLBP