Zhigang You

MRI and Quantification of Draining Lymph Node Function in Inflammatory Arthritis

Abstract:  While erosion and tissue necrosis are the end‐stage result of inflammatory arthritis, factors that can predict their initiation and severity are unknown. In an effort to identify these prognostic factors we developed contrast‐enhanced (CE)‐magnetic resonance imaging (MRI) for the mouse knee to assess the pathogenesis of inflammatory arthritis. Using this approach to study synovitis and draining lymph node (LN) function we first demonstrated that the LNs of TNF‐Tg mice at 5 months are significantly larger and have greater enhancement in comparison to wild‐type (WT) mice. This difference correlated with the abundance of dilated LYVE‐1+ sinuses in the draining LNs. Dynamic CE‐MRI further demonstrated differences between TNF‐Tg and WT mice in the kinetics of LN enhancement. We established an LN capacity (LNcap) measurement that is a function of both volume and CE. We demonstrated that TNF‐Tg mice have a 15‐fold increase over WT levels at 5 months age (P < 0.001). Amelioration of arthritis with anti‐TNF therapy resulted in a significant decrease in LNcap (P < 0.0001) that approached WT levels within 4 weeks. Interestingly, this functional decrease was not associated with a reduction of lymphatic vessels, which persist after therapy in both LNs and synovium. To assess the relationship between draining LN function and synovitis, a regression analysis was performed that demonstrated a significant negative correlation (R2= 0.63, P= 0.01) between LNcap and synovial volume. TNF‐Tg mice with a lower LNcap display an accelerated progression of arthritis. These results indicate a protective function of enhanced lymphatic drainage in inflammatory arthritis.

A four-element phased array coil for high resolution and parallel MR imaging of the knee.

A four-element phased array coil for MR imaging of the knee was designed, built and tested for clinical use at 1.5 Tesla. In routine imaging, it provides over twofold increase in signal-to-noise (SNR) compared to two commercially available knee coils, and supports higher spatial image resolution. The phased array knee coil was also tested for its compatibility with parallel MR imaging that reduces imaging time by several folds over conventional MR technique. Results obtained using SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique shows that our phased array knee coil can be used with parallel MR imaging. These improvements may enhance knee diagnosis with higher image quality and reduced scan time.

Chronic axial compression of the mouse tail segment induces MRI bone marrow edema changes that correlate with increased marrow vasculature and cellularity.

Magnetic resonance imaging (MRI) of bone marrow edema (BME) has been found to be helpful in the diagnosis of back pain attributed to degenerative disk disease (DDD) and spondyloarthropathy (SA), but its interpretation is limited by a lack of knowledge of its nature and natural history. We assessed effects of compressive forces to mouse tail segments of WT and TNF‐Tg mice with SA, via contrast enhanced‐MRI and histology. Normalized marrow contrast enhancement (NMCE) of uninstrumented WT vertebrae significantly decrease, threefold (p < 0.01) from 8 to 12 weeks of age, while the NMCE of TNF‐Tg vertebrae remained elevated. Compressive loading (6× body weight) increased NMCE twofold (p < 0.02) within 2 weeks in WT tails, which was equal to 6× loaded TNF‐Tg tails within 4 weeks. Histology confirmed degenerative changes and that load‐induced NMCE corresponded to increased vascular sinus tissue (35 ± 3% vs. 19 ± 3%; p < 0.01) and cellularity (4,235 ± 886 vs.1,468 ± 320 cells/mm2; p < 0.01) for the loaded versus unloaded WT, respectively. However, micro‐computed tomography (CT) analyses failed to detect significant load‐induced changes to bone. While the bone marrow of loaded WT and TNF‐Tg vertebrae were similar, histology demonstrated mild cellular infiltrate and increased osteoclastic resorption in the WT tails versus severe inflammatory‐erosive arthritis in TNF‐Tg joints. Significant (p < 0.05) decreases in cortical and trabecular bone volume in uninstrumented TNF‐Tg versus WT vertebrae were confirmed by micro‐CT. Thus, chronic load‐induced DDD causes BME signals in vertebrae similar to those observed from SA, and both DDD and SA signals correlate with a conversion from yellow to red marrow, with increased vascularity.

High‐resolution uniform MR imaging of finger joints using a dedicated RF coil at 3T

To develop a dedicated radiofrequency (RF) coil for high‐resolution magnetic resonance imaging (MRI) of finger joints at 3T to improve diagnostic evaluation of arthritic diseases.

TNF is required for the induction but not the maintenance of compression-induced BME signals in murine tail vertebrae: Limitations of anti-TNF therapy for degenerative disc disease

While bone marrow edema (BME) is diagnostic of spondyloarthropathy, its nature remains poorly understood. In contrast, BME in ankylosing spondylitis is caused by tumor necrosis factor (TNF)‐induced vascular and cellular changes. To investigate the relationship between chronic compression and TNF signaling in compression‐induced BME we utilized a tail vertebrae compression model with WT, TNF‐Tg, and TNFR1&2−/− mice to evaluate: (i) healing following release of chronic compression, (ii) induction of BME in the absence of TNFR, and (iii) efficacy of anti‐TNF therapy. Compression‐induced normalized marrow contrast enhancement (NMCE) in WT was significantly decreased threefold (p < 0.01) within 2 weeks of release, while the NMCE values in TNF‐Tg vertebrae remained elevated, but had a significant decrease (p < 0.05) by 6 weeks after the release of compression. TNFR1&2−/− mice were resistant to compression‐induced BME. Anti‐TNF therapy did not affect NMCE versus placebo. Histological examination revealed that NMCE values significantly correlated with marrow vascularity and cellularity (p < 0.05), which account for 76% of the variability of NMCE. Collectively, these data demonstrate a critical role for TNF in the induction of chronic compression‐induced BME, but not in its maintenance. Amelioration of BME is achieved through biomechanical stability, but is not affected by anti‐TNF therapy.

High‐resolution interleaved water‐fat MR imaging of finger joints with chemical‐shift elimination

To study the use of an interleaved water‐fat (IWF) sequence with a custom‐made radiofrequency (RF) coil for high‐resolution imaging of arthritic finger joints.