Molecular characterization of rheumatoid arthritis with magnetic resonance imaging

Abstract

Several recent advances in the field of magnetic resonance imaging (MRI) may transform the detection and monitoring of rheumatoid arthritis (RA). These advances depict both anatomic and molecular alterations from RA. Previous techniques could detect specific end products of metabolism in vitro or were limited to providing anatomic information. This review focuses on the novel molecular imaging techniques of hyperpolarized carbon-13 MRI, MRI with iron-labeled probes, and fusion of MRI with positron emission tomography. These new imaging approaches go beyond the anatomic description of RA and lend new information into the status of this disease by giving molecular information.

Figure 1

Quantitative metabolic maps in an arthritic rat after injection of hyperpolarized ¹³C-pyruvate show increased lactate production in the arthritic right paw as measured by the lactate-to-pyruvate ratio (Lac/Pyr). The color bar indicates relative levels of Lac/Pyr. Red color is the maximum signal intensity for ¹³C-pyruvate = 1485 au, ¹³C-lactate = 674 au, and Lac/Pyr = 1.03. ¹H-MRI shows soft tissue swelling in the arthritic right (R) paw in comparison to the control left (L) paw and the region of interest analysis applied for the metabolic maps. T=tail, au=arbitrary units. Reproduced with permission from MacKenzie JD, et al. Radiology 2011.

Figure 2

Spectroscopic profiles from single 2.5 × 2.5 × 10 mm voxels in control and arthritic tissues in one rat. Increased ¹³C-lactate production is demonstrated in the plantar surface of the arthritic right paw (lactate-to-pyruvate ratio = 0.70) in comparison to the control left paw (= 0.57), tail (= 0.37), and tissues away from the site of arthritis induction in the dorsal right paw (= 0.57). Arrow indicates alanine production in the control left paw, but no alanine is observed in the arthritic paw. Reproduced with permission from MacKenzie JD, et al. Radiology 2011.

Figure 3

Transverse T2*-weighted fast gradient-echo images (1000/15; flip angle, 25°) show T2* effects at USPIO-enhanced MR imaging of macrophage activity in antigen-induced arthritis in rabbits. (a) Precontrast image shows joint effusion (arrow) that is surrounded by a thickened synovium (arrowhead). (b) Postcontrast image (24 hours after USPIO administration) shows susceptibility effects (arrow) within the synovium (arrowhead), representing USPIO uptake in phagocytic-active macrophages. Signal intensity of bone marrow (*) is decreased in comparison to that in a, which is caused by USPIO uptake by the mononuclear phagocyte system within the bone marrow. Reproduced with permission from Lutz AM, et al. Radiology 2004.

Figure 3

Transverse T2*-weighted fast gradient-echo images (1000/15; flip angle, 25°) show T2* effects at USPIO-enhanced MR imaging of macrophage activity in antigen-induced arthritis in rabbits. (a) Precontrast image shows joint effusion (arrow) that is surrounded by a thickened synovium (arrowhead). (b) Postcontrast image (24 hours after USPIO administration) shows susceptibility effects (arrow) within the synovium (arrowhead), representing USPIO uptake in phagocytic-active macrophages. Signal intensity of bone marrow (*) is decreased in comparison to that in a, which is caused by USPIO uptake by the mononuclear phagocyte system within the bone marrow. Reproduced with permission from Lutz AM, et al. Radiology 2004.

Figure 4

Fusion of high-resolution ¹⁸F-FDG-PET with MRI for an RA therapy responder. Images were generated using the clinical MRI and high resolution PET/CT sequential scanning approach. The top row shows images from baseline while the bottom row depicts images at 4 weeks after the initiation of treatment. Figures (a) and (c) depict representative axial sections from a pre-contrast T₁-weighted MR image of the patient's wrist, (b) and (d) show the same section from the T₁-weighted MR image acquired post-administration of a gadolinium-based contrast agent, and (c) and (f) demonstrate the MRI-PET fusion images of the same section. Red arrows show synovitis in the carpal region, green arrows indicate inflammation at sites of erosions while the blue arrows indicate inflammation at the base of the thumb (corresponding to osteoarthritis). Dramatic reductions in synovitis and metabolic activity at sites of erosions were measured from MRI-PET at 4 weeks and correlated with the rheumatologist's score obtained at the patient's 3-month standard-of-care visit.