Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
High Resolution Magnetic Resonance Imaging for the Assessment of Dermal Fibrosis in a Pre-Clinical Model of Scleroderma.
Jones1, Helen, Derrett-Smith1, Emma, Denton1, Chris P., Abraham1, David, Bou-Gharios2, George, So3, Po-Wah
Scleroderma (Systemic Sclerosis, Ssc) is a heterogeneous chronic multisystem rheumatological disorder. A hallmark of the disease is excessive dermal and organ scarring. Dermal biopsies have been extensively used to evaluate the degree of scarring and development of fibrosis. This invasive technique only allows a 'snapshot' of one region of the skin. Here we used a pre-clinical model of scleroderma to assess the potential for applying non-invasive magnetic resonance imaging for the analysis of dermal fibrosis. We analysed structural changes in the skin of mice harbouring mutations which resulted in modulation of the TGFb signalling pathways (TbRIIDkfib mice) by histological staining and high resolution magnetic resonance imaging (MRI) scans to detect and compare changes in skin architecture and composition.
Full-thickness dermal biopsies were taken from the dorsal region of adult mice and fixed in formalin. Samples were placed within a customised holder containing Fomblin Perfluorosolv PFS-1, positioned within a quadrature volume coil, and MRI performed on a 7 Tesla VMRIS scanner using a gradient echo MRI sequence with the following parameters: repetition time, 250ms; echo time, 2.5ms; field of view, 10 × 10mm; matrix size, 128 × 128; 40° flip angle and 14 consecutive transverse, 1mm thick slices (in plane resolution 78mm). Thickness of the dermis and panniculus adiposus were measured using Image J with 7 measurements, distributed across the image, for each sample. After scanning, samples were embedded in paraffin and serial sections (3 microns) were stained with H&E for routine histology and an extracellular matrix stain for the degree of fibrosis (Picrosirius red). Images were captured at 10x magnification. Thickness of the dermis and panniculus adiposus were measured using Axioskop software with at least 30 measurements, distributed across the length, for each sample.
Histological staining allows easy identification of the dermal and hypodermal compartments, namely the dermis, panniculus adiposus, panniculus carnosus, subcutaneous loose connective tissue, and subcutaneous muscle. Comparison with the MRI images showed that high resolution MRI can also distinguish between dermis, panniculus adiposus, panniculus carnosus, subcutaneous loose connective tissue, and subcutaneous muscle. By gradient echo MRI dermis, panniculus carnosus, and muscle have higher signal intensities than panniculus adiposus and loose connective tissue.
Thickness measurements of dermis and panniculus adiposus are consistent between histological and MRI images, however a better correspondence is observed for dermis than panniculus adiposus. TbRIIDkfib mutant mice were found to have thicker dermis than wildtype mice (p<0.01), which is consistent with the known increase in collagen in the skin of the mutant mice. Interestingly, thickening of the dermis is also accompanied by a thickening of the underlying panniculus adiposus (p<0.01).
High resolution MRI scanning is a promising non-invasive technique for assessing dermal fibrosis that warrants further optimisation in pre-clinical models prior to translation into a clinical setting.
To cite this abstract, please use the following information:
Jones, Helen, Derrett-Smith, Emma, Denton, Chris P., Abraham, David, Bou-Gharios, George, So, Po-Wah; High Resolution Magnetic Resonance Imaging for the Assessment of Dermal Fibrosis in a Pre-Clinical Model of Scleroderma. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1995