Proton Density Fat Fraction Spine MRI for Differentiation of Erosive Vertebral Endplate Degeneration and Infectious Spondylitis

Vertebral Modic type 1 (MT1) degeneration may mimic infectious disease on conventional spine magnetic resonance imaging (MRI), potentially leading to additional costly and invasive investigations. This study evaluated the diagnostic performance of the proton density fat fraction (PDFF) for distinguishing MT1 degenerative endplate changes from infectious spondylitis. A total of 31 and 22 patients with equivocal diagnosis of MT1 degeneration and infectious spondylitis, respectively, were retrospectively enrolled in this IRB-approved retrospective study and examined with a chemical-shift encoding (CSE)-based water-fat 3D six-echo modified Dixon sequence in addition to routine clinical spine MRI. Diagnostic reference standard was established according to histopathology or clinical and imaging follow-up. Intravertebral PDFF [%] and PDFFratio (i.e., vertebral endplate PDFF/normal vertebrae PDFF) were calculated voxel-wise within the single most prominent edematous bone marrow lesion per patient and examined for differences between MT1 degeneration and infectious spondylitis. Mean PDFF and PDFFratio of infectious spondylitis were significantly lower compared to MT1 degenerative changes (mean PDFF, 4.28 ± 3.12% vs. 35.29 ± 17.15% [p < 0.001]; PDFFratio, 0.09 ± 0.06 vs. 0.67 ± 0.37 [p < 0.001]). The areas under the curve (AUC) and diagnostic accuracies were 0.977 (p < 0.001) and 98.1% (cut-off at 12.9%) for PDFF and 0.971 (p < 0.001) and 98.1% (cut-off at 0.27) for PDFFratio. Our data suggest that quantitative evaluation of vertebral PDFF can provide a high diagnostic accuracy for differentiating erosive MT1 endplate changes from infectious spondylitis.

Degenerative disc disease in young adults: cytokine profile and angiogenic factors

Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p < 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p < 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p < 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p < 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p < 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p < 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.

CORRELATION BETWEEN THE MODIC I SIGN AND IMAGES OF VERTEBRAL INSTABILITY

ABSTRACT The lumbar region is highly affected by degenerative diseases and can be symptomatic as a result of inflammatory processes of the disc or segmental vertebral instability (SVI), according to concepts by White and Panjabi. Magnetic resonance imaging (MRI) and dynamic radiographs can be used to evaluate it. Objective: To determine whether images of Modic type I lesions are compatible with radiological vertebral instability. Methods: The MRIs and dynamic radiographs of 100 patients with a mean age of 46.94 years, 65 of whom were women and 35 of whom were men, were studied to evaluate the reaction of endplates according to Modic and SVI at levels L2-L3, L3-L4, L4-L5 and L5-S1. They were divided into 3 groups: A- Modic I and SVI; B- Modic I without SVI; and C- Without Modic I and SVI. Sex, age and type of disc were evaluated. Result: 46 Modic I lesions and 24 cases of SVI were recognized. There were 5 patients in Group A (OR 0.23, p=0.006), 38 in Group B; and 19 in Group C. No direct relationship between age and Modic I and/or SVI was observed. Pfirrmann grade 5 discs are 4.6 times more likely to present a Modic I signal. The most affected disc was L3-L4 for the Modic signal and L4-L5 with respect to the SVI, translational instability being more frequent. Conclusions: Modic type changes, identified by magnetic resonance, are clinically relevant in relation to low back pain, but their presence does not confirm either translational or angular instability. Level of evidence III; Cross-sectional cohort.

Improving effect of microendoscopic decompression surgery on low back pain in patients with lumbar spinal stenosis and predictive factors of postoperative residual low back pain: a single-center retrospective study

Background Although there are reports on the effectiveness of microendoscopic laminotomy using a spinal endoscope as decompression surgery for lumbar spinal stenosis, predicting the improvement of low back pain (LBP) still poses a challenge, and no clear index has been established. This study aimed to investigate whether microendoscopic laminotomy for lumbar spinal stenosis improves low back pain and determine the preoperative predictors of residual LBP. Methods In this single-center retrospective study, we examined 202 consecutive patients who underwent microendoscopic laminotomy for lumbar spinal stenosis with a preoperative visual analog scale (VAS) score for LBP of ≥40 mm. The lumbar spine Japanese Orthopaedic Association (JOA), and VAS scores for LBP, leg pain (LP), and leg numbness (LN) were examined before and at 1 year after surgery. Patients with a 1-year postoperative LBP-VAS of ≥25 mm composed the residual LBP group. The preoperative predictive factors associated with postoperative residual LBP were analyzed. Results JOA scores improved from 14.1 preoperatively to 20.2 postoperatively (p < 0.001), LBP-VAS improved from 66.7 to 29.7 mm (p < 0.001), LP-VAS improved from 63.8 to 31.2 mm (p < 0.001), and LN-VAS improved from 63.3 to 34.2 mm (p < 0.001). Ninety-eight patients (48.5%) had a postoperative LBP-VAS of ≥25 mm. Multiple logistic regression analysis revealed that Modic type 1 change (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.68–18.68; p = 0.005), preoperative VAS for LBP ≥ 70 mm (OR, 2.19; 95% CI, 1.17–4.08; p = 0.014), and female sex (OR, 1.98; 95% CI, 1.09–3.89; p = 0.047) were preoperative predictors of residual LBP. Conclusion Microendoscopic decompression surgery had an ameliorating effect on LBP in lumbar spinal stenosis. Modic type 1 change, preoperative VAS for LBP, and female sex were predictors of postoperative residual LBP, which may be a useful index for surgical procedure selection.

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

OP0083 INFECTIOUS AND AUTOINFLAMMATORY MODIC TYPE 1 CHANGES HAVE DIFFERENT PATHOMECHANISMS

Background:Modic type 1 changes (MC1) are vertebral bone marrow (BM) edema that associate with non-specific low back pain (LBP). Two etiologies have been described. In the infectious etiology the anaerobic aerotolerant Cutibacterium acnes (C. acnes) invades damaged intervertebral discs (IVDs) resulting in disc infection and endplate damage, which leads to the evocation of an immune response. In the autoinflammatory etiology disc and endplate damage lead to the exposure of immune privileged disc cells and matrix to leukocytes, thereby evoking an immune response in the BM. Different etiologies require different treatment strategies. However, it is unknown if etiology-specific pathological mechanisms exist.Objectives:The aim of this study was to identify etiology-specific dysregulated pathways of MC1 and to perform in-depth analysis of immune cell populations of the autoinflammatory etiology.Methods:BM aspirates and biopsies were obtained from LBP patients with MC1 undergoing spinal fusion. Aspirates/biopsies were taken prior screw insertion through the pedicle screw trajectory. From each patient, a MC1 and an intra-patient control aspiration/biopsy from the adjacent vertebral level was taken. If C. acnes in IVDs adjacent to MC1 were detected by anaerobic bacterial culture, patients were assigned to the infectious, otherwise to the autoinflammatory etiology.Total RNA was isolated from aspirates and sequenced (Novaseq) (infectious n=3 + 3, autoinflammatory n=5 + 5). Genes were considered as differentially expressed (DEG) if p-value < 0.01 and log2fc > ± 0.5. Gene ontology (GO) enrichment was performed in R (GOseq), gene set enrichment analysis (GSEA) with GSEA software.Changes in cell populations of the autoinflammatory etiology were analyzed with single cell RNA sequencing (scRNAseq): Control and MC1 biopsies (n=1 + 1) were digested, CD45+CD66b- mononuclear cells isolated with fluorescence activated cell sorting (FACS), and 10000 cells were sequenced (10x Genomics). Seurat R toolkit was used for quality-control, clustering, and differential expression analysis.Transcriptomic changes (n=5 + 5) of CD45+CD66b+ neutrophils isolated with flow cytometry from aspirates were analyzed as for total bulk RNAseq. Neutrophil activation (n=3 + 3) was measured as CD66b+ expression with flow cytometry. CD66bhigh and CD66blow fractions in MC1 and control neutrophils were compared with paired t-test.Results:Comparing MC1 to control in total bulk RNAseq, 204 DEG in the autoinflammatory and 444 DEG in the infectious etiology were identified with only 67 shared genes (Fig. 1a). GO enrichment revealed “T-cell activation” (p = 2.50E-03) in the autoinflammatory and “complement activation, classical pathway” (p=1.1E-25) in the infectious etiology as top enriched upregulated biological processes (BP) (Fig 1b). ScRNAseq of autoinflammatory MC1 showed an overrepresentation of T-cells (p= 1.00E-34, OR=1.54) and myelocytes (neutrophil progenitor cells) (p=4.00E-05, OR=2.27) indicating an increased demand of these cells (Fig. 1c). Bulk RNAseq analysis of neutrophils from the autoinflammatory etiology revealed an activated, pro-inflammatory phenotype (Fig 1d), which was confirmed with more CD66bhigh neutrophils in MC1 (+11.13 ± 2.71%, p=0.02) (Fig. 1e).Figure 1.(a) Venn diagram of DEG from total bulk RNAseq (b) Top enriched upregulated BP of autoinflammatory (left) and infectious (right) etiology (c) Cell clustering of autoinflammatory MC1 BM (d) Enrichment of “inflammatory response” gene set in autoinflammatory MC1 neutrophils (e) Representative histogram of CD66b+ expression in MC1 and control neutrophils.Conclusion:Autoinflammatory and infectious etiologies of MC1 have different pathological mechanisms. T-cell and neutrophil activation seem to be important in the autoinflammatory etiology. This has clinical implication as it could be explored for diagnostic approaches to distinguish the two MC1 etiologies and supports developing targeted treatments for both etiologies.Disclosure of Interests:None declared

Imaging in the Diagnosis of Nonspecific Pyogenic Spondylodiskitis

The prevalence of nonspecific pyogenic spondylodiskitis, associated with both a high morbidity and a high mortality, has increased in the last few decades. The diagnosis is often delayed because of the nonspecific clinical manifestation at the early stage. The reliability of radiographs is limited, particularly in early stage after the onset of infection. Computed tomography (CT) can reliably assess the bony condition with the possibility of spatial visualization. Contrast enhancement supports the detection of affected soft tissue. Magnetic resonance imaging (MRI) continues to be the gold standard in the diagnosis of spondylodiskitis. Sophisticated investigation protocols supported by gadolinium enhancement secure the diagnosis. MRI has a high resolution without radiation exposure. Different nuclear investigation techniques extend the diagnostic options. Reports of 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) are particularly promising to confirm the diagnosis. The drawback of the reduced image quality with respect to detailed anatomical information can be overcome by a combined simultaneous acquisition of CT or MRI. With respect to one of the greatest challenges, the differentiation between degenerative changes (Modic type 1) and infection at an early stage using differentiated MRI protocols and FDG-PET is promising. This overview presents a concise state-of-the-art look at radiologic investigations in case of suspected nonspecific pyogenic spondylodiskitis with the focus on a pragmatic approach.