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

Real-Time Quantum Noise Suppression In Very Low-Dose Fluoroscopy

Fluoroscopy provides real-time X-ray screening of patient's organs and of various radiopaque objects, which make it an invaluable tool for many interventional procedures. For this reason, the number of fluoroscopy screenings has experienced a consistent growth in the last decades. However, this trend has raised many concerns about the increase in X-ray exposure, as even low-dose procedures turned out to be not as safe as they were considered, thus demanding a rigorous monitoring of the X-ray dose delivered to the patients and to the exposed medical staff. In this context, the use of very low-dose protocols would be extremely beneficial. Nonetheless, this would result in very noisy images, which need to be suitably denoised in real-time to support interventional procedures. Simple smoothing filters tend to produce blurring effects that undermines the visibility of object boundaries, which is essential for the human eye to understand the imaged scene. Therefore, some denoising strategies embed noise statistics-based criteria to improve their denoising performances. This dissertation focuses on the Noise Variance Conditioned Average (NVCA) algorithm, which takes advantage of the a priori knowledge of quantum noise statistics to perform noise reduction while preserving the edges and has already outperformed many state-of-the-art methods in the denoising of images corrupted by quantum noise, while also being suitable for real-time hardware implementation. Different issues are addressed that currently limit the actual use of very low-dose protocols in clinical practice, e.g. the evaluation of actual performances of denoising algorithms in very low-dose conditions, the optimization of tuning parameters to obtain the best denoising performances, the design of an index to properly measure the quality of X-ray images, and the assessment of an a priori noise characterization approach to account for time-varying noise statistics due to changes of X-ray tube settings. An improved NVCA algorithm is also presented, along with its real-time hardware implementation on a Field Programmable Gate Array (FPGA). The novel algorithm provides more efficient noise reduction performances also for low-contrast moving objects, thus relaxing the trade-off between noise reduction and edge preservation, while providing a further reduction of hardware complexity, which allows for low usage of logic resources also on small FPGA platforms. The results presented in this dissertation provide the means for future studies aimed at embedding the NVCA algorithm in commercial fluoroscopic devices to accomplish real-time denoising of very low-dose X-ray images, which would foster their actual use in clinical practice

Estimation of skeletal kinematics in freely moving rodents

Forming a complete picture of the relationship between neural activity and skeletal kinematics requires quantification of skeletal joint biomechanics during free behavior; however, without detailed knowledge of the underlying skeletal motion, inferring limb kinematics using surface-tracking approaches is difficult, especially for animals where the relationship between the surface and underlying skeleton changes during motion. Here we developed a videography-based method enabling detailed three-dimensional kinematic quantification of an anatomically defined skeleton in untethered freely behaving rats and mice. This skeleton-based model was constrained using anatomical principles and joint motion limits and provided skeletal pose estimates for a range of body sizes, even when limbs were occluded. Model-inferred limb positions and joint kinematics during gait and gap-crossing behaviors were verified by direct measurement of either limb placement or limb kinematics using inertial measurement units. Together we show that complex decision-making behaviors can be accurately reconstructed at the level of skeletal kinematics using our anatomically constrained model

Nanofibrous Disc-Like Angle Ply Structure for Total Disc Replacement in a Small Animal Model

Low back pain affects 85% of the population and carries a socioeconomic price tag of $100 billion USD per year. Lumbar intervertebral disc disease is strongly implicated as a causative factor in back pain, as degeneration, which is ubiquitous in the population, leads to loss of normal spine function. For these reasons, our lab has developed disc-like angle ply structures (DAPS) for total disc replacement. These cell-seeded replacements are designed to match the natural hierarchical structure and function of the native disc and correct spinal kinematics after end-stage disc disease. In this dissertation, I describe the development of a rat caudal spine (tail) model of total disc replacement as a platform to evaluate DAPS in vivo; an external fixation system that immobilized caudal vertebrae at the site of implantation was required for DAPS retention and a radiopaque scaffold was developed to confirm intervertebral DAPS positioning. A detailed analysis of the DAPS in vitro growth trajectory was performed to select the optimum pre-culture duration before implantation. Cell-seeded DAPS were subsequently implanted in the rat tail and evaluated by histological, mechanical, and MRI analyses. DAPS successfully restored the mechanical properties of the native motion segment in compression, providing the first evidence of the efficacy of engineered disc replacements. Adaptations of the implant to the in vivo environment were identified; there was a reduction in glycosaminoglycan after implantation, structural modifications to the NP material, and no evidence of vertebral integration. In tackling the first of these issues, a pre-culture strategy that primed DAPS for the in vivo environment was developed; using a rat subcutaneous model, implant phenotype was best conserved post-implantation using a pre-culture strategy with a transient high dose of TGF-b3. Future work will address maintenance of NP structure, vertebral integration and scaling up to human sizes. In my work, the most promising finding was that DAPS replicated compressive motion segment mechanical properties after implantation supporting the idea that engineered biological disc replacement is a possibility for clinical treatment of advanced disc disease

The state-of-the-art in ultrasound-guided spine interventions.

During the last two decades, intra-operative ultrasound (iUS) imaging has been employed for various surgical procedures of the spine, including spinal fusion and needle injections. Accurate and efficient registration of pre-operative computed tomography or magnetic resonance images with iUS images are key elements in the success of iUS-based spine navigation. While widely investigated in research, iUS-based spine navigation has not yet been established in the clinic. This is due to several factors including the lack of a standard methodology for the assessment of accuracy, robustness, reliability, and usability of the registration method. To address these issues, we present a systematic review of the state-of-the-art techniques for iUS-guided registration in spinal image-guided surgery (IGS). The review follows a new taxonomy based on the four steps involved in the surgical workflow that include pre-processing, registration initialization, estimation of the required patient to image transformation, and a visualization process. We provide a detailed analysis of the measurements in terms of accuracy, robustness, reliability, and usability that need to be met during the evaluation of a spinal IGS framework. Although this review is focused on spinal navigation, we expect similar evaluation criteria to be relevant for other IGS applications

Shape/image registration for medical imaging : novel algorithms and applications.

This dissertation looks at two different categories of the registration approaches: Shape registration, and Image registration. It also considers the applications of these approaches into the medical imaging field. Shape registration is an important problem in computer vision, computer graphics and medical imaging. It has been handled in different manners in many applications like shapebased segmentation, shape recognition, and tracking. Image registration is the process of overlaying two or more images of the same scene taken at different times, from different viewpoints, and/or by different sensors. Many image processing applications like remote sensing, fusion of medical images, and computer-aided surgery need image registration. This study deals with two different applications in the field of medical image analysis. The first one is related to shape-based segmentation of the human vertebral bodies (VBs). The vertebra consists of the VB, spinous, and other anatomical regions. Spinous pedicles, and ribs should not be included in the bone mineral density (BMD) measurements. The VB segmentation is not an easy task since the ribs have similar gray level information. This dissertation investigates two different segmentation approaches. Both of them are obeying the variational shape-based segmentation frameworks. The first approach deals with two dimensional (2D) case. This segmentation approach starts with obtaining the initial segmentation using the intensity/spatial interaction models. Then, shape model is registered to the image domain. Finally, the optimal segmentation is obtained using the optimization of an energy functional which integrating the shape model with the intensity information. The second one is a 3D simultaneous segmentation and registration approach. The information of the intensity is handled by embedding a Willmore flow into the level set segmentation framework. Then the shape variations are estimated using a new distance probabilistic model. The experimental results show that the segmentation accuracy of the framework are much higher than other alternatives. Applications on BMD measurements of vertebral body are given to illustrate the accuracy of the proposed segmentation approach. The second application is related to the field of computer-aided surgery, specifically on ankle fusion surgery. The long-term goal of this work is to apply this technique to ankle fusion surgery to determine the proper size and orientation of the screws that are used for fusing the bones together. In addition, we try to localize the best bone region to fix these screws. To achieve these goals, the 2D-3D registration is introduced. The role of 2D-3D registration is to enhance the quality of the surgical procedure in terms of time and accuracy, and would greatly reduce the need for repeated surgeries; thus, saving the patients time, expense, and trauma