A porcine model of intervertebral disc degeneration induced by annular injury characterized with magnetic resonance imaging and histopathological findings

2008 ◽  
Vol 8 (5) ◽  
pp. 450-457 ◽  
Author(s):  
Seung-Hwan Yoon ◽  
Masashi Miyazaki ◽  
Soon-Woo Hong ◽  
Ben Tow ◽  
Yuichiro Morishita ◽  
...  

Object Appropriate animal models of disc degeneration are critical for the study of proposed interventions as well as to further delineate the degenerative process. The purpose of this study was to characterize a porcine model for disc degeneration confirmed on magnetic resonance (MR) imaging studies and histological analysis. Methods Twelve miniature pigs were used (weight 48–65 kg) to study degeneration in the lumbar spine. Under fluoroscopic guidance, the disc was percutaneously punctured with a 3.2-mm-diameter trephine to a 5-mm depth into the annulus fibrosus. Control and experimental levels were randomized among 6 levels in the lumbar spine. The unlesioned spinal levels were used as controls and were compared with lesioned levels. Magnetic resonance imaging grading and disc height were serially recorded preoperatively, and at 5, 8, 19, 32, and 39 weeks postoperatively. The animals were killed in groups of 3 at 7, 18, 32, and 41 weeks postinjury, and the discs were examined histopathologically. Results Consistent, sequential, and progressive degeneration of the annular injury was observed on MR imaging and histopathological studies from the time of injury to the final time point. The disc height and the disc height index also sequentially decreased from the time of the injury in a consistent manner. The uninjured control levels did not show any progressive degeneration and maintained their normal state. Conclusions Based on MR imaging and histopathological findings, the authors demonstrated and characterized a reliable model of sequential disc degeneration in miniature pigs with percutaneous injury to the annulus fibrosus. In the early stages, as soon as 5 weeks after injury, significant disc degeneration was seen on MR imaging grading with decreases in disc height. This degeneration did not improve by the final time point of 39 weeks.

Author(s):  
Daniel H. Cortes ◽  
Lachlan J. Smith ◽  
Sung M. Moon ◽  
Jeremy F. Magland ◽  
Alexander C. Wright ◽  
...  

Intervertebral disc degeneration is characterized by a progressive cascade of structural, biochemical and biomechanical changes affecting the annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). These changes are considered to contribute to the onset of back pain. It has been shown that mechanical properties of the AF and NP change significantly with degeneration [1,2]. Therefore, mechanical properties have the potential to serve as a biomarker for diagnosis of disc degeneration. Currently, disc degeneration is diagnosed based on the detection of structural and compositional changes using MRI, X-ray, discography and other imaging techniques. These methods, however, do not measure directly the mechanical properties of the extracellular matrix of the disc. Magnetic Resonance Elastography (MRE) is a technique that has been used to measure in vivo mechanical properties of soft tissue by applying a mechanical vibration and measuring displacements with a motion-sensitized MRI pulse sequence [3]. The mechanical properties (e.g., the shear modulus) are calculated from the displacement field using an inverse method. Since the applied displacements are in the order of few microns, fibers may not be stretched enough to remove crimping. Therefore, it is unknown if the anisotropy of the AF due to the contribution of the fibers is detectable using MRE. The objective of this study is twofold: to measure shear properties of AF in different orientations to determine the degree of AF anisotropy observable by MRE, and to identify the contribution of different AF constituents to the measured shear modulus by applying different biochemical treatments.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Sertac Kirnaz ◽  
Stephen Sloan ◽  
Christoph Wipplinger ◽  
Franziska Anna Schmidt ◽  
Roger Hartl ◽  
...  

Abstract INTRODUCTION The objective of the current study is to assess the efficacy of combined annulus fibrosus (AF) using a high-density collagen (HDC) gel and nucleus pulposus (NP) repair using a hyaluronic acid (HA) gel in an in Vivo sheep model. METHODS We performed an anterolateral, retroperitoneal prepsoas approach to access the IVDs L1-6 in a total of 8 skeletally mature Finn sheep. IVDs were randomized into 5 groups: (1) intact, (2) injured via 3 × 10 mm box annulotomy and removal of 200 mg of NP, (3) injury and HDC gel patch for AF repair, (4) injury and injection of a HA gel into the NP, and (5) injury and HDC AF repair and NP HA replacement. At 6 wk postoperatively, sheep were sacrificed and underwent postmortem 3T-MRI scans as well as gross anatomical and histological evaluation. Disc height index (DHI) analysis and Pfirrmann grading (PG) were performed on each segment using MR images. RESULTS Intact control discs were not degenerated and had an average PG of 1 while injured, and untreated discs had a significant degeneration with an average PG of 3. Discs receiving the combined injection and collagen AF patch individually showed fewer signs of degeneration than injured alone, and the combined treatment resulted in the least amount of degeneration with PG not significantly different from the intact controls. DHI confirmed the trends seen in the PG, where injured discs lost 20% of the intact disc height, the individual NP and AF repairs restored 5% to 10% of intact disc height, and the combined repairs preserved 90% of the intact disc height. CONCLUSION PG and DHI results demonstrate that individual NP and AF repairs are able to prevent disc degeneration better than no treatment at all; however, the greatest preservation of disc health was seen with combined AF and NP repairs.


2019 ◽  
Vol 48 (7) ◽  
pp. 20180466
Author(s):  
Nathália R. Gomes ◽  
Juliano D.S. Albergaria ◽  
Jonathas A. de S. Henriques ◽  
Tânia M.P. Amaral ◽  
Evandro N. Abdo ◽  
...  

Objectives: To evaluate bone repair of an osseous defect in a rat animal model through fractal analysis and radiopacity analysis in radiographic images. Methods: 120 rats were subjected to extraction of their first molar and divided into four groups (n = 6/group) according to the material used for bone grafting: mineralized bovine bone, demineralized bovine bone (DBB), blood clot (BC - control) or Bio-Oss® (BO). The animals were sacrificed after 1, 7, 14, 21 and 49 days and subjected to radiographic evaluation. For fractal analysis (FA), a square regionof interest of 30 × 30 pixels was used, and radiopacity was measured as the mean gray scale (MGS) value for three points of 5 × 5 pixels in the apical, medial and coronal regions of the defect. Histomorphometric evaluation was realized as the gold standard for bone neo-formation and maturation of the new osseous matrix. Results: Histomorphometric evaluation suggested that DBB showed faster mineralized deposition and resulted in more mature bone at the final time point of evaluation. Mineralized bovine bone and Bio-Oss presented similar results. The mineralized groups did not show significant differences in bone maturation. The radiopacity analysis revealed a significant difference (p < 0.05) between the DBB and blood clot groups at the final time point. FA did not show any significant differences at the final time point. Conclusions: Mean gray scale seemed to be more effective for the quantification of bone repair than FA in the demineralized group in this animal model. Results for the mineralized groups did not reveal a significant difference, leading to the conclusion that both methods are effective.


2021 ◽  
Vol 42 ◽  
pp. 166-178
Author(s):  
N Bouhsina ◽  
◽  
C Decante ◽  
JB Hardel ◽  
S Madec ◽  
...  

Sheep are one of the many animal models used to investigate the pathophysiology of disc degeneration and the regenerative strategies for intervertebral disc (IVD) disease. To date, few studies have thoroughly explored ageing of ovine lumbar IVDs. Hence, the objective of the present study was to concomitantly assess the development of spontaneous age-related lumbar IVD degeneration in sheep using X-ray, magnetic resonance imaging (MRI) as well as histological analyses. 8 young ewes (< 48 months old) and 4 skeletally mature ewes (> 48 months old) were included. Disc height, Pfirrmann and modified Pfirrmann grades as well as T2-wsi and T2 times were assessed by X-ray and MRI. The modified Boos score was also determined using histology sections. Pfirrmann (2 to 3) and modified Pfirrmann (2 to 4) grades as well as Boos scores (7 to 13) gradually increased with ageing, while T2-weighted signal intensity (1.18 to 0.75), T2 relaxation time (114.36 to 70.65 ms) and disc height (4.1 to 3.2 mm) decreased significantly. All the imaging modalities strongly correlated with the histology (p < 0.0001). The present study described the suitability of sheep as a model of age-related IVD degeneration by correlation of histological tissue alterations with the changes observed using X-ray and MRI. Given the structural similarities with humans, the study demonstrated that sheep warrant being considered as a pertinent animal model to investigate IVD regenerative strategies without induction of degeneration.


2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Tamsyn Derrick ◽  
Athumani M. Ramadhani ◽  
David Macleod ◽  
Patrick Massae ◽  
Elias Mafuru ◽  
...  

ABSTRACT Trachoma is initiated during childhood following repeated conjunctival infection with Chlamydia trachomatis, which causes a chronic inflammatory response in some individuals that leads to scarring and in-turning of the eyelids in later life. There is currently no treatment to halt the progression of scarring trachoma due to an incomplete understanding of disease pathogenesis. A cohort study was performed in northern Tanzania in 616 children aged 6 to 10 years at enrollment. Every 3 months for 4 years, children were examined for clinical signs of trachoma, and conjunctival swabs were collected for C. trachomatis detection and to analyze the expression of 46 immunofibrogenic genes. Data were analyzed in relation to progressive scarring status between baseline and the final time point. Genes that were significantly associated with scarring progression included those encoding proinflammatory chemokines (CXCL5, CCL20, CXCL13, and CCL18), cytokines (IL23A, IL19, and IL1B), matrix modifiers (MMP12 and SPARCL1), immune regulators (IDO1, SOCS3, and IL10), and a proinflammatory antimicrobial peptide (S100A7). In response to C. trachomatis infection, IL23A and PDGF were significantly upregulated in scarring progressors relative to in nonprogressors. Our findings highlight the importance of innate proinflammatory signals from the epithelium and implicate interleukin 23A (IL-23A)-responsive cells in driving trachomatous scarring, with potential key mechanistic roles for PDGFB, MMP12, and SPARCL1 in orchestrating fibrosis.


2018 ◽  
Vol 26 (3) ◽  
pp. 230949901879271
Author(s):  
T David Luo ◽  
Alejandro Marquez-Lara ◽  
Zachary K Zabarsky ◽  
Jeremy B Vines ◽  
Katie C Mowry ◽  
...  

Purpose: Various animal models have been proposed to mimic the pathophysiologic process of intervertebral disc degeneration, a leading cause of back pain. The purpose of this study is to describe a minimally invasive technique via percutaneous needle puncture of the annulus fibrosus in New Zealand white rabbits. Methods: Under fluoroscopic guidance, an 18-gauge spinal needle was inserted 2 cm lateral to the midline spinous process. The needle was slowly advanced at approximately 45° angle until it was adjacent to the L5/L6 disc space. Lateral and anteroposterior views were used to verify correct needle position before advancing into the nucleus pulposus. The rabbits underwent weekly X-rays for 4 weeks to assess disc height index. MRI T2 relaxation was evaluated at week four to assess morphological changes. Discs were histologically graded on a 12-point scale to assess degeneration and compared to discs obtained from uninjured rabbits. Results: There were no complications associated with the percutaneous needle puncture procedure. All animals survived the duration of the experiment. Four weeks after injury, the disc height had progressively narrowed to approximately 50% of baseline. MRI assessment at the 4-week time point demonstrated a mean T2 relaxation time at the L5/L6 level that was 20.9% of the T2 relaxation time at the uninjured L4/L5 disc level ( p < 0.001). Histological analysis demonstrated lamellar disorganization of the annulus and decreased cellularity and proteoglycan content within the injured nucleus compared to uninjured control discs. Conclusion: The present study demonstrated a reliable technique of inducing an annular tear via a percutaneous needle puncture. Compared to open surgical approaches, the percutaneous model produces similar progressive disc degeneration while minimizing harm to the animal subjects. Clinical Relevance: The present study establishes a technique for the introduction of novel therapeutic agents to treat disc degeneration that may translate to future clinical trials.


2007 ◽  
Vol 107 (3) ◽  
pp. 600-609 ◽  
Author(s):  
Robert G. Whitmore ◽  
Jaroslaw Krejza ◽  
Gurpreet S. Kapoor ◽  
Jason Huse ◽  
John H. Woo ◽  
...  

Object Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms. Methods Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade. Results In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively. Conclusions Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.


Author(s):  
Ali Ahmed Abou Elmaaty ◽  
Carmen Ali Zarad ◽  
Tamer Ibrahim Belal ◽  
Tamer Sabry Elserafy

Abstract Background Idiopathic intracranial hypertension (IIH) is a neurological disorder of unknown etiology and ambiguous pathophysiology due to cerebrospinal fluid dysregulation. This study is designed to evaluate the role of brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) in diagnosis of IIH, to clarify the nature and extent of cognitive deficits, and to detect if there is a correlation between radiology, clinical findings, and cognitive dysfunctions in those patients. Results The study included 34 patients and 34 age-, sex-, body mass index (BMI)-, and education-matched healthy control subjects. MR brain imaging and Montreal cognitive assessment (MoCA) test were used for both groups. MRI and MRV sensitivity for IIH diagnosis were 85.2% and 85.3% with 100% and 94.1% specificity respectively. 44.1% had cognitive impairment, memory was the most affected domain, followed by attention, abstraction, and orientation with statistically significantly lower total MoCA score (p < 0.005). Domain comparisons reveal a statistically significantly lower memory/delayed recall (p < 0.001) and abstract scores (p < 0.007) in IIH cases versus control subjects. In comparing patients with cognitive impairment (CI) versus those without CI, there were statistically significantly higher CI in low education level, presence of diplopia, hormonal contraceptive use, abnormal MRI brain, papilledema grades, BMI, and opening pressure. Conclusions Presence of more than or equal 3 MR imaging findings, bilateral transverse sinus stenosis, and less than or equal 4 combined conduit score increase the specificity and sensitivity of MRI and MRV for IIH diagnosis. IIH had detrimental effect on different cognitive domains especially when patient have low education level, diplopia, papilledema ≥ grade III, high OP ≥ 61.5 cm H2O, and BMI ≥ 34 Kg/m2 with abnormal MRI and MRV findings.


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