3D lumbar spine intervertebral disc segmentation and compression simulation from MRI using shape-aware models.

Study 1. The Roles of IL-19, IL-20 on Intervertebral Disc Herniation and Degenerative Lumbar Spondylolisthesis The inflammatory reaction after intervertebral disc herniation (HIVD) was considered as the major cause of low back pain and sciatica. IL-19 and IL-20, members of IL-10 family, are involved in various inflammatory diseases. However, little is known on how IL-19 and IL-20 affect the inflammation, healing process, and degeneration of spine after intervertebral disc injury. We reported the expression of IL-20 and its receptors in the primarily cultured disc cells as well as in human herniated intervertebral disc (HIVD) tissues. Disc cells express IL-20 receptors and are targeted by IL-20. In vitro, IL-1β induced the expression of IL-20, and IL-20 combined with IL-1β induced the expression of various cytokines, chemokines, angiogenetic factors, and matrix metalloproteinases (MMPs) in human disc cells. Therefore, IL-20 together with IL-1β enhances the inflammatory process after disc injury, and IL-20 may contribute to the pathogenesis of HIVD. Degenerative lumbar spondylolisthesis (DLS) results from disc injury, which usually occurs at the L4/L5 level after the facet-joint locking mechanism fails. The etiology of DLS is multifactorial, and includes spinal instability, neurological compromise and inflammation. In clinical practice, symptoms are not well correlated with the severity of degeneration and neural compression on MRIs of patients with DLS. Inflammation may play an important role in the pathogenesis of DLS; however, expression of IL-19 and IL-20 and their pathophysiological function in DLS has not been explored. Thus, we explored if IL-19 and IL-20 were associated with DLS. We found that IL-19, IL-20, IL-20R1 and IL-20R2, TNF-α, IL-1β and MCP-1 were co-localized in tissue samples of degenerated discs, facet joints, and ligamentum flavum retrieved from patients with DLS. The expression of IL-19 and IL-20 is associated with the expression of the inflammatory cytokines, TNF-α and IL-1β and the chemokines, MCP-1 and IL-8. In vitro, IL-19 and IL-20 induced the expression of proinflammatory cytokines, chemokine, and angiogenesis under CoCl2-mimicked hypoxia condition in the primarily cultured human disc cells, which isolated from degenerated disc tissues of patients with DLS. Therefore, IL-19 and IL-20 may contribute to the inflammatory process in discs, facet joints, and the ligamentum flavum in patients with DLS；IL-19 and IL-20 may be involved in the pathogenesis of DLS. Study 2. The in vivo Biological Effects of Intra-discal RhBMP-2 on the Injured Intervertebral Disc RhBMP-2, a potent osteoinductive and chondroinductive factor, has been approved for use in human anterior spinal fusion and can promote cartilage repair. We found that BMP-2 can be expressed in the human herniated disc specimen. However, the in vivo response of intra-discal rhBMP-2 on the injured IVDs is not clear. We found that various degrees of degenerative change around the injured disc space in our rabbit disc injury model. More severe spondylosis, such as spur formation, was found in the groups treated with rhBMP-2. The pathological findings revealed that rhBMP-2 promotes angiogenesis and inflammation after disc injury; which are known as the first two stages of bone incorporation for fusion. Therefore, rhBMP-2 might contribute to the injury response, healing process and subsequent degeneration after disc injury. Study 3. Factors Affecting Disability and Physical Function in Degenerative Lumbar Spondylolisthesis Axially-loaded magnetic resonance image (MRI) is a useful diagnostic tool, enabling detection of dynamic or occult changes of spinal disorders by simulating the upright position under normal gravity and mimicking the condition of axial compression in the lumbar spine. Except the roles of IL-19 and IL-20 in the inflammation process of degenerative lumbar spondylolisthesis (DLS), we aimed to further analyze the critical biomechanical factors responsible for the disability and physical function of patients with DLS using axially-loaded MRI, and to investigate the effect of axial loading on the morphology of the spine and the spinal canal. All patients underwent unloaded and axially-loaded MRI. We measured the predictors on MRI, including the differences of disc height (DH), sagittal translation (ST), segmental angulation (SA), and dural sac cross-sectional area (DCSA) at L4-5 between the unloaded and axially-loaded condition, as well as pre-load and post-load lumbar lordotic angles (LLA) at L1-5. We discovered that angular instability is correlated with physical disability and physical function for patients with L4-5 DLS in an axially-loaded magnetic resonance image (MRI); the post-load lumbar lordotic curve angle is also well correlated with physical function for patients with L4-5 DLS. Segmental angulation of L4-5 can be a good indicator of disability in patients with L4-5 DLS. In conclusion, we discovered that IL-19, IL-20, and BMP-2 may be the key factors to modulate inflammation, healing process and degeneration of spine after intervertebral disc injury. Besides, we also discovered that angular instability of intervertebral disc is correlated with physical disability and physical function for patients with L4-5 DLS.

Scoliotic and herniated human intervertebral disc tissue obtained intraoperatively was cultured, and the medium was analyzed for the production of monocyte chemoattractant protein-1 and interleukin-8. This study was conducted to determine whether the human intervertebral disc is capable of spontaneous production of the chemokines monocyte chemoattractant protein-1 and interleukin-8. Lumbar disc herniations undergo spontaneous regression with time. This is believed to occur via macrophage-mediated phagocytosis of herniated disc material. Monocyte chemoattractant protein-1, a chemotactic agent for macrophages, has recently been identified in rat intervertebral disc tissue. Disc material obtained from patients undergoing surgery for scoliosis and sciatica was cultured using a serumless technique, and the medium was subsequently analyzed for levels of monocyte chemoattractant protein-1 and interleukin-8. Monocyte chemoattractant protein-1 and IL-8 were detected in both control and herniated disc specimens. Noncontained herniations produced higher levels of chemokines than those with an intact anulus. Human intervertebral disc tissue is capable of spontaneously producing the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8. These are chemotactic for macrophages and capillaries and may explain the ingrowth of granulation tissue seen in spontaneous disc herniation resorption.

Background: Nucleus pulposus (NP) cell senescence is an important cellular feature within the degenerative disc. It is known that a very acidic niche exists in the degenerative disc, which participates in regulating disc cell viability and matrix metabolism. Objective: The present study was aimed to investigate the role and potential signaling transduction pathway of an acidic pH in regulating NP cell senescence. Methods: Rat NP cells were cultured in an acidic pH of 7.2 close to that in a healthy disc (Control group) or in an acidic pH of 6.2 close to that in a severe degenerative disc (Experiment group) for 10 days. Additionally, the experimental NP cells were incubated along with the inhibitor SB203580 to analyze the role of p38 MAPK pathway in this process. Results: Compared with the control NP cells, experimental NP cells showed a suppressed cell proliferation potency, an increased G0/G1 phase fraction whereas a decreased S-phase fraction and a declined telomerase activity, an up-regulated expression of senescence-related molecules (p16 and p53), and a down-regulated expression of matrix-related moleucles (aggrecan and collagen II). Further analysis showed that inhibition of the p38 MAPK pathway partly reversed effects of acidic pH of 6.2 on the experimental NP cells. Conclusion: The very acidic niche identified in a severe degenerative disc promotes NP cell senescence through regulating the p38 MAPK pathway. The present study provides a new mechanism that drives NP cell senescence during disc degeneration.

Segmentation and classification of intervertebral disc using capsule stacked autoencoder

Introduction An association between cartilaginous endplate (CEP) defects and intervertebral disk (IVD) degeneration has been previously suggested in animal and cadaveric studies. There have been no previous reports in the literature that describe the use of ultrashort time-to-echo (UTE) magnetic resonance imaging (MRI) to assess the CEP in humans in vivo. As such, the purpose of this study was to report the feasibility of the UTE MRI technique to assess CEP defects in humans in vivo using and to assess their relationship with IVD degeneration. Materials and Methods Nine volunteer subjects (mean age 43.9 years; range: 22 to 61 years) were recruited, representing 54 IVDs and 108 CEPs. The subjects underwent T2-weighted and UTE MRI to assess for the presence and severity of IVD degeneration, and for the presence of CEP defects, respectively, from T12 to S1. Intervertebral disk degeneration was graded according to the Schneiderman et al classification on T2-weighted MRI. CEP defects were defined on UTE MRI as discontinuity of high-signal over 4 consecutive images and were independently assessed by two observers. Results Total 37% out of 108 (34.3%) CEPs had defects, which mainly occurred at T12/L1, L1/L2, and L4/L5 ( p = 0.008). Multivariate logistic regression revealed that lower BMI ( p = 0.009) and younger ( p = 0.034) individuals had a decreased likelihood of having CEP defects. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration ( p = 0.036).A higher prevalence of degenerated IVDs with CEP defects were found at L4/5 and L5/S1, while degenerated IVDs with no CEP defects were found throughout the whole lumbar region. Mean IVD degeneration scores of the L4/5 and L5/S1 levels with CEP defects were higher in comparison to those with no CEP defects. Conclusion Our study demonstrates the feasibility of using UTE MRI in humans in vivo to assess the integrity of the CEP. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration. In the lower lumbar region, more severe degeneration was found to occur in the IVDs with CEP defects than in those without defects. Such imaging technology may broaden the understanding of IVD degeneration and facilitate management options that target IVD repair/regeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared

The objective of this work is to study the effect of the backpack on the components of the spine system of a child, know the effect of an eccentric force on the intervertebral discs, the creating a 3D model of the spine of child of 38 kg overall weight under the effect of three eccentric load (P2, P3, P4) plus P1 compression load and calculated by the element method ends, For the boundary conditions we fixed the sacrum (Embedding the sacrum). We propose in this section to draw up a comprehensive study of the distributions of stresses and normal elastic strain of Von Mises in the intervertebral discs based on loads supported. The results show that the stress and strain of Von Mises are highest and concentrated in four intervertebral discs (D1, D2, D3 and D4), which causes a problem that calls (herniated disc). We concluded that the cause of the posterior load, a 300 mm lever arm with a 150N force present maximum Von Mises stresses concentrated in four intervertebral discs (D1, D2, D3, D4), which justifies the distance between the load which is the point of application of the load and the axis of the spine plays a very important role in increasing the solicitation of the latter.

BackgroundSpine magnetic resonance image (MRI) plays a very important role in the diagnosis of various spinal diseases, such as disc degeneration, scoliosis, and osteoporosis. Accurate localization and segmentation of the intervertebral disc (IVD) in spine MRI can help accelerate the diagnosis time and assist in the treatment by providing quantitative parameters. In this paper, a method based on Gabor filter bank is proposed for IVD localization and segmentation.MethodsFirst, the structural features of IVDs are extracted using a Gabor filter bank. Second, the Gabor features of spine are calculated and spinal curves are detected. Third, the Gabor feature images (GFI) of IVDs are calculated and adjusted according to the spinal curves. Fourth, the IVDs are localized by clustering analysis with GFI. Finally, an optimum grayscale-based algorithm with self-adaptive threshold, combined with the localization results and Gabor features of the spine, is performed for IVDs segmentation.ResultsThe proposed method is verified by an MRI dataset consisting of 278 IVDs from 37 patients. The accuracy of localization is 98.23 % and the dice similarity index for segmentation evaluation is 0.9237.ConclusionsThe proposed Gabor filter based method is effective for IVD localization and segmentation. It would be useful in computer-aided diagnosis of IVD diseases and computer-assisted spine surgery.

We have recently found a high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation might regulate biological activities in the IVD. The objective of this study was therefore to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: the annulus fibrosus (AF) and nucleus pulposus (NP). ATP treatment significantly promotes ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in three-dimensional agarose culture. A significant increase in ECM accumulation has been found in AF cells at a lower ATP treatment level (20 μM) compared with NP cells (100 μM), indicating that AF cells are more sensitive to extracellular ATP than NP cells. NP cells also exhibit higher ECM accumulation and intracellular ATP than AF cells under control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, ATP treatment also augments the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via a molecular pathway, but also increases energy supply to fuel that process.

Objective. To implement the interlaminar lateral approach for extraction of herniated discs (HD) in the cervical spine.Materials and methods. During 2012–2015 in Regional psychoneurological hospital 56 patients with cervical HD were operated. There were 22 females, 36 males among them. Disc herniation at the CV–CVI level occurred in 21 cases, CVI–CVII in 20 cases. The main disease signs were cervicalgia, monoradiculopathy. Fifty patients with medial hernia were operated using anterior cervical microscopic discectomy approach to HP extraction and intervertebral cage implantation (PEEK material). Six patients with lateral hernia were operated using posterior interlaminar cervical microdiscectomy. Anterior approach was performed by a standard method using CODMAN retractor, high-speed drill Stryker TPS. The posterior interlaminar approach was performed using paramedian incision 3 cm, intermuscular approach to the posterior lateral mass and arch on the affected side with Medtronic Metrix system followed by interlaminectomy performed by high-speed drill not more than 1 cm that was rather enough for hernia extraction from under nerve root.Results. In all cases we managed to achieve the regression of radicular and cervicalgia syndromes. No complications were fixed during both surgical approaches. There was no difference observed in duration of surgical intervention using both methods, which was about (64±12) min. All patients were verticalized and activated in 3–4 hours after surgery.Conclusion. Cervical microdiscectomy is a standard method for cervical HD surgery. The posterior interlaminar approach is an effective method used for lateral herniations, especially sequestered ones. It promotes the preservation of intervertebral disc and reduction of the total cost of surgery due to no necessity to use the implants-prosthesis. We suppose the posterior cervical microdiscectomy of lateral, sequestered intervertebral disc herniations in cervical spine to become a standard method of treatment.

Objective To discuss diagnosis and anterior surgical treatment of hyperextensian cervical spine injury combined with intervertebral disk injury. Methods A retrospective study was done on clinical data of 27 patients who suffered from hyperextension cervical spine injury combined with intervertebral disk injury to analyze their age distribution, clinical symptomes, X-ray and MRi manifesta-tions and perioperative intervertebral disk injury. All patients were treated with discectomy, strut bone grafting within vertebral bodies and internal fixation with titanium plate. The clinical outcomes were evalu-ated by using Frankel scale and ASIA motor score (AMS). Results Both MRI and X-ray detected following abnormal pathological changes in all patients: rupture of anterior longitudinal ligament, horizon-tal tear of disk, intervertebral disk hernia, compression and edema of spinal cord. The follow-up lasted for 9-32 months (average 17.5 months), which showed that all patients got improvement for 1-3 scales except that one patient with Frankel A had no improvement in neurological function. Compared with AMS on admission, both AMS at two months after surgery and at final follow-up was increased significantly, with recovery rate of AMS for 44.9% and 68.1%, respectively. There found no hardware related compli-cations such as implant loosening, defluxion or breakage. Bone fusion was found in all fixation segments. Conclusions MRI and X-ray are important examination means for hyperextension cervical spine injury combined with intervertebral disk injury. On a specified diagnosis, anterior surgical treatment should be done early and can get satisfactory recovery of spinal cord function. Key words: Spinal cord injury; Cervical spine; Intervertebral disk; Diagnosis,computer-assisted

BackgroundIntervertebral disc herniation (IVDH) involves displacement of the intervertebral disc secondary to disc degeneration and is extremely common in dachshunds. Clinical signs include pain with or without paresis or paralysis. Mortality rate is high and some cases are left with permanent disability even after treatment. Aims of this study were twofold: Firstly, to investigate whether neutering, i.e. gonadectomy, is associated with increased risk of IVDH in dachshunds, and secondly to investigate whether age of neutering alters risk of IVDH in this breed.Information was obtained for 1964 dachshunds from the owner survey, “Dachslife 2015”. For dachshunds that were ≥ 3 years and < 10 years old at the time of the survey (1073 individuals) incidence of IVDH was compared between early-neutered (< 12 months), late-neutered (> 12 months) and entire animals of each gender.ResultsNeutered females were at significantly higher risk of IVDH than entire females (risk ratio 1.81, 95% CI 1.28–2.54). For males, incidence of IVDH in neutered as compared with entire dachshunds was increased but this difference was not quite statistically significant (risk ratio 1.38, 95% CI 0.96–1.99).For both genders, this study demonstrated significantly increased risk of IVDH in early-neutered dachshunds (before 12 months old) as compared with those neutered late (after 12 months old). For early neutered males, risk ratio was 1.54 (95% CI 1.07–2.22). For early-neutered females, risk ratio was 2.12 (95% CI 1.44–3.11).ConclusionResults from this retrospective study suggest that gonadectomy, especially if performed before 12 months old, increases risk of IVDH in this breed. Decisions regarding neutering should be made on an individual basis, taking a range of pros and cons into account. Considering the high prevalence, morbidity and mortality of IVDH in dachshunds, increased IVDH risk associated with neutering is a key factor to consider in deciding whether and when to neuter.

MRI-based relationships between spine pathology, intervertebral disc degeneration, and muscle fatty infiltration in chondrodystrophic and non-chondrodystrophic dogs

Multi-joint disease pathologies in the lumbar spine, including ligamentum flavum (LF) hypertrophy and intervertebral disc (IVD) bulging or herniation contribute to lumbar spinal stenosis (LSS), a highly prevalent condition characterized by symptomatic narrowing of the spinal canal. Clinical hypertrophic LF is characterized by a loss of elastic fibers and increase in collagen fibers, resulting in fibrotic thickening and scar formation. In this study, we created an injury model to test the hypothesis that LF needle scrape injury in the rat will result in hypertrophy of the LF characterized by altered tissue geometry, matrix organization, composition and inflammation. An initial pilot study was conducted to evaluate effect of needle size. Results indicate that LF needle scrape injury using a 22G needle produced upregulation of the pro-inflammatory cytokine Il6 at 1 week post injury, and increased expression of Ctgf and Tgfb1 at 8 weeks post injury, along with persistent presence of infiltrating macrophages at 1, 3, and 8 weeks post injury. LF integrity was also altered, evidenced by increases in LF tissue thickness and loss of elastic tissue by 8 weeks post injury. Persistent LF injury also produced multi-joint effects in the lumbar IVD, including disc height loss at the injury and adjacent to injury level, with degenerative IVD changes observed in the adjacent level. These results demonstrate that LF scrape injury in the rat produces structural and molecular features of LF hypertrophy and IVD height and histological changes, dependent on level. This model may be useful for testing of therapeutic interventions for treatment of LSS and IVD degeneration associated with LF hypertrophy.

PurposeIn patients with lumbar disc herniation (LDH), the herniated intervertebral disc (IVD) can be spontaneously absorbed without surgical intervention (herein referred to as “resorption”). However, current studies provide unclear explanations of the mechanism of LDH resorption, and the summary of predictive factors is not comprehensive enough. This review aimed to summarize predictive factors associated with LDH resorption based on current evidence, thereby providing clinical guidance for therapeutic decision making.MethodsA comprehensive literature search was performed using PubMed, Web of Science, Embase, and the Cochrane Library from database inception to July 2024. The search was performed using the terms “spontaneous”, “regression”, “resorption”, “remission”, “absorption”, “herniation”, and “disc”. Manual searches were also performed to broaden the literature search. Studies were included if they reported at least one potential predictor of resorption in patients with LDH and provided follow-up imaging assessments (CT/MRI) to define resorption outcomes, along with the criteria used to determine the presence or absence of imaging resorption. Two reviewers independently searched the relevant literature and the ROBINS-I tool were used to assess the quality.ResultsThe literature search yielded 1115 publications, of which 22 were finally included. The review suggested that the probability of resorption in LDH can be predicted by five aspects: clinical factors, type and size of the LDH, composition of the herniated IVD, imaging features of LDH, and spinal physiology. One limitation of this review is the lack of high-quality prospective studies among the included research, which may affect the accuracy of the findings.ConclusionThe probability of resorption in LDH can be predicted based on five aspects. This helps clinicians preferentially select LDH cases with a high probability of resorption for conservative treatment, which is of positive significance for improving the success rate of conservative treatment in patients with LDH. However, due to the lack of high-quality prospective studies for support, large-scale prospective studies are necessary to assess the accuracy of these predictive factors for LDH resorption.

IntroductionIntervertebral disc (IVD) degeneration is considered a major underlying factor in the pathogenesis of chronic low back pain. Although the healthy IVD is both avascular and aneural, during degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD, which may contribute to the pain. The mechanisms underlying neural ingrowth are, however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves seeking their synaptic target. This study aimed to identify whether members of the Class 3 semaphorins were expressed by chondrocyte-like cells of the IVD addressing the hypothesis that they may play a role in repelling axons surrounding the healthy disc, thus maintaining its aneural condition.MethodsHuman IVD samples were investigated using reverse transcription polymerase chain reaction (RT-PCR) to identify gene expression of sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A protein was also localised within sections of normal and degenerate human IVD and immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31 to correlate semaphorin 3A expression with nerve and blood vessel ingrowth, respectively.ResultsSema3A protein was expressed highly in the healthy disc, primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A.ConclusionsThis study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.