ISP Poster
- 1. A Quantitative Radiological Analysis of GNE Myopathy Aria Ghaffari1 , Evrim Turkbey M.D2 , Ron Summers M.D, PhD2 Nuria Carrillo-Carrasco M.D3 Abstract 1 M14 Research Day, Georgetown University School of Medicine, Washington, D.C. 2 CIPS, Radiology and Imaging Science, NIH, MD 3 NCATS, NIH, MD Introduction Materials and Methods Conclusions References Georgetown University 1. Eisenberg I, Avidan N, et al. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nature Genetics. Vol 29 (2001) 83-87 2. Keppler OT, et al. UDP-GlcNAc 2-Epimerase: A Regulator of Cell Surface Sialylation. Science Mag. Vol 284 (1999) 1372-1376. 3. Z. Argov, R. Yarom, “Rimmed vacuole myopathy” sparing the quadriceps. A unique disorder in Iranian Jews, J. Neurol. Sci. 64 (1984) 33–43. 4. Kuo GP, Carrino JA. Skeletal muscle imaging and inflammatory myopathies. Curr Opin Rheumatol. 2007;19:530Y535. 5. M. Huizing, D.M. Krasnewich, Hereditary Inclusion Body Myopathy: A decade of progress, Biochimica et Biophysica Acta 1792 (2009) 881-887. 6. O’Connell MJ, Powell T, Brennan D, et al. Whole-body MR imaging in the diagnosis of polymyositis. AJR Am J Roentgenol. 2002;179:967Y971. 7. Park J, Vansant J, et al. Dermatomyositis: Correlative MR Imaging and P-31 Spectroscopy for Quantitative Characterization of Inflammatory Disease. Radiology. Vol 177 (1990) Num 2 473-479. 8. Liu G, Jong Y, Chiang C, Jaw T. Duchenne Muscular Dystrophy: MR Grading System with Functional Correlation. Radiology. Vol 186 (1993) Num 2 475-480. 9. Rosenthal D I, Barton N W, et al. Quantitative Imaging of Gaucher Disease. Radiology. Vol 185 (1992) Num 3 841-845. 10. Huizing M, Malicdan MV, Krasnewich DM, Manoli I, Carrillo-Carrasco N. GNE Myopathy. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. OMMBID - The Online Metabolic and Molecular Bases of Inherited Diseases. New York: McGraw-Hill; 2013. Background: GNE myopathy, previously known as Hereditary Inclusion Body Myopathy (HIBM), is a slowly progressive muscle disease with no treatment available. In preparation for clinical trials, reliable endpoints are being explored to monitor efficacy. We studied the use of quantitative imaging as a potential useful endpoint. Methods: As part of a single center natural history study of GNE myopathy, patients underwent lower extremity muscle MRI at baseline and at follow-up evaluations. Axial T1-weighted images were reviewed and reformatted to differentiate muscle and fat composition within the thigh. Results: Fourteen patients underwent baseline and 6-month follow up MRI. We found a statistically significant change in cross-sectional muscle area in the left medial and posterior compartments of the thigh. All other compartments showed no significant change. Conclusions: Our data is consistent with the expected chronic progression of disease in patients with GNE Myopathy. GNE myopathy is a rare genetic muscle disease caused by mutation in GNE, the gene that encodes for the key enzyme in the sialic acid biosynthesis pathway (1,2(. It is characterized by progressive muscle weakness, secondary to muscle atrophy and subsequent fatty replacement (3,4). The quadriceps muscles are the last to be affected in the lower extremities (5). Other musculoskeletal diseases have successfully been monitored by quantitative imaging (6,7,8,9). In preparation for clinical trials for GNE myopathy, we aim to establish a reliable method of quantitative imaging to monitor muscle composition in patients. Patient Selection Individuals between 18 and 80 years old with a confirmed genetic diagnosis of GNE myopathy and who do not require the use of a wheelchair are eligible for the study. Muscle MRI is performed at baseline and at 6, 12, 18, and 24-month follow-up visits. Patients who had baseline and 6-month follow-up scans available were selected for analysis. Magnetic Resonance Imaging Protocol Lower extremity MRI studies were performed with a 3T MR scanner (Verio; Siemens, Erlangen, Germany). T1-weighted axial and coronal MR sequences of the lower extremities were acquired with the following parameters: TR: 700.00 ms, TE: 20.00 ms, slice thickness: 8.00 mm. Defining the Mid-Femoral Level: On the coronal T1-weighted series, we defined the mid-femoral level as halfway between the superior aspect of the femoral head and inferior aspect of the medial condyle. An active registration line was used to select the mid-femoral slice on axial images using Carestream Vue PACS (Rochester, NY) (Image 1). Measuring total cross-sectional area: Each predefined muscle compartment was delineated with an ROI to measure the surface area at three consecutive mid-femoral slices using SyngoVia workstation (Siemens, Erlangen, Germany) on the T1-weighted axial series (Image 2). Differentiating muscle and fat composition using thresholding: Each thigh muscle compartment at the mid-femoral level that has mixed fat and muscle tissue with visual assessment was tresholded to separate the pixels of muscle from fat using AW software (GE Health care, Milwaukee, WI) (Images 3,). The amount of fat was calculated by subtracting the muscle area from total surface area of the compartment. Images 1 3 2 Fig. 1(A-C). Box-and-whisker plots of mean mid-femoral cross-sectional area of muscle composition in patients who underwent baseline and 6 month follow up MRI scans. Plots display the following data from left to right: right thigh at baseline; right thigh at 6 months; left thigh at baseline; left thigh at 6 months. A) Data collected from ROI 1, defined as the cross-sectional muscle area of the anterior compartment excluding the rectus femoris. B) Data collected from ROI 2, defined as the cross-sectional muscle area of the rectus femoris. C) ROI 3, defined as the cumulative cross-sectional muscle area of the medial and posterior compartments. Preliminary data showed no significant change of the muscle area in multiple compartments at the mid-femoral level within a 6 month period. There was a modest decrease in muscle area in the left posterior and medial compartments of the thigh. Our data is consistent with the expected slow progression of GNE myopathy. Poster produced by Faculty & Curriculum Support, Georgetown University School of Medicine Quantitative Analysis We quantified the muscle and fat-replaced mass of the thigh by measuring the cross- sectional areas at three consecutive mid-femoral slices. We have predefined three muscle compartments as regions of interest (ROIs): 1) the anterior compartment of the thigh excluding the rectus femoris muscle, 2) the rectus femoris muscle, and 3) the medial and posterior compartments. Then, we thresholded the images to differentiate the fat and muscle composition within the ROIs. Mean values of three slices were used in the analysis. Results and Discussion A Figure 1 Fourteen patients (mean age: 43 years; 13 female) underwent a baseline and 6-month follow-up muscle MRI. The mean cross-sectional muscle area of the right side at baseline and at 6 month follow up was 57.0 cm2 and 55.9 cm2 for ROI 1 (p=0.25); 2.9 cm2 and 2.7 cm2 for ROI 2 (p=0.27); 6.1 cm2 and 5.4 cm2 for ROI 3 (p=0.15), respectively. On the left side, these values were 53.8 cm2 and 53.9 cm2 for ROI 1 (p=0.92); 2.7 cm2 and 2.5 cm2 for ROI 2 (p=0.26); 7.5 cm2 and 5.7 cm2 for ROI 3 (p=0.02), respectively. The muscle area change within 6 months was not statistically significant in all muscle groups except the left posterior and medial compartments of the thigh. This finding is consistent with the previous studies describing the loss of muscle mass in these compartments at earlier stages of disease while the anterior compartment is unaffected (3). This study has limitations. The available 6-month follow-up data is not enough to detect change in this slowly progressive disease. The study is ongoing and further follow-up will be obtained. The sample size is limited because of the rare of the disease; however, 50 patients will be recruited in this study. B C Images 1-3. 1) Coronal slice with femoral length measurement (left), corresponding axial slice (right). 2) Measuring total cross-sectional area. 3) Selection of an ROI for thresholding (left), fat pixels subtracted out leaving muscle cross- sectional area (right).