STUDY DESIGN: Observational comparative study. PURPOSE: To compare fractional anisotropy (FA) maps with T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) of intervertebral discs in healthy volunteers and patients to develop a predictive disc health scale. OVERVIEW OF LITERATURE: T2-weighted magnetic resonance imaging (MRI) is not sensitive to early morphological changes and provides no quantitative biomarker profile for early degeneration. METHODS: We examined 59 healthy controls and 59 patients with back pain by MRI using T2 relaxometry and diffusion tensor imaging (DTI). Each group was divided into three age subgroups: A (<30 years, n=12); B (30–50 years, n=26); and C (>50 years, n=21). We obtained FA values for AF and NP and T2 values for NP for each intervertebral disc. Furthermore, we calculated the FA (AF/NP) ratios. RESULTS: We categorized 590 intervertebral discs from 118 participants, 566 of which were analyzed with T2 relaxometry and DTI. The T2 values were as follows: subgroup A, 55.8±4.4 ms; B, 48.5±6.9 ms; C, 45.8±8.7 ms (p<0.050). The T2 values for the healthy controls of the subgroups A, B, and C were >120 ms, 90–100 ms, and 70 ms, respectively (p<0.001). Control subgroup A had higher T2 values and AF/NP ratios than subgroups B and C; the AF values were not significantly different. Control subgroup B had higher T2 values and AF/NP ratios than subgroup C but lower FA (NP). CONCLUSIONS: FA maps of the AF/NP ratio and T2 values of NP are potential microstructure biomarkers of normal and degenerating discs and can help detect early degeneration using a predictive disc health score on a continuous scale.
Anisotropy ; Back Pain ; Biomarkers ; Diffusion Tensor Imaging ; Healthy Volunteers ; Humans ; Intervertebral Disc Degeneration ; Intervertebral Disc ; Magnetic Resonance Imaging

OBJECTIVE Pancreatic ductal adenocarcinoma (PDAC), a lethal cancer in need of new, effective therapies, has a unique tumor microenvironment characterized by a dense fibrotic stroma (desmoplasia) that is generated by pancreatic cancer- associated fibroblasts (PCAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). METHEDS and RESULTS Hypothe?sizing that G protein-coupled receptors (GPCRs) may regulate PCAFs, we used an unbiased GPCRomic array approach to compare GPCR expression in PCAFs, PFs and PSCs and identified 82 GPCRs commonly expressed by PCAFs derived from primary tumors of five PDAC patients. We discovered that PCAFs have increased expression of numerous GPCRs, in particular aGPCR with much higher expression in PCAFs compared to both PFs and PSCs. Immunohistochemistry revealed increased expression of this GPCR in PDAC tumors. Co- culture of PSCs with PDAC cells or incubation with TNFα induced its expression. Activation of the GPCR in PCAF sincreased expression of interleukin-6 (IL-6) via a cAMP/PKA/CREB signaling pathway. GPCR knockdown with siRNA diminished IL-6 production and secretionby PCAFs and ability of PCAF conditioned media to enhance proliferation of PDAC cells. CONCLUSION We conclude that PDAC cells induce expression by PCAFs of a novel GPCR, resulting in increased IL-6 production by PCAFs and promotion of PDAC cell proliferation. This PCAF-expressed GPCR thus contributes to PDAC cell-PCAF interaction and as such, may be a novel therapeutic target for PDAC tumors.