1296 AJR:204, June 2015 Quantifcation of Bone Marrow Involvement in Treated Gaucher Disease With Proton MR Spectroscopy: Correlation With Bone Marrow MRI Scores and Clinical Status Diego Jaramillo 1,2 Maria A. Bedoya 1 Dah-Jyuu Wang 1 Andres H. Pena 3 Jorge Delgado 1 Camilo Jaimes 4 Victor Ho-Fung 1,2 Paige Kaplan 5, 6 Jaramillo D, Bedoya MA, Wang DJ, et al. 1 Department of Radiology, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104. Address correspondence to D. Jaramillo (jaramillo@email.chop.edu). 2 Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 3 Department of Radiology, SUNY Stony Brook University Hospital, Stony Brook, NY. 4 Department of Radiology, Massachusetts General Hospital, Boston, MA. 5 Section of Metabolic Disease, The Children’s Hospital of Philadelphia, Philadelphia, PA. 6 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. PA. Pediatric Imaging • Original Research AJR 2015; 204:1296–1302 0361–803X/15/2046–1296 © American Roentgen Ray Society Keywords: bone marrow, Gaucher disease, MRI, MR spectroscopy DOI:10.2214/AJR.14.13563 Received July 23, 2014; accepted after revision September 21, 2014. D. Jaramillo has received a research grant from Genzyme Corporation, a Sanofi Company, to enable this pilot study to be done. P. Kaplan is a member of the Advisory Board for Gaucher Disease and Mucopolysaccharidosis, which is supported by Genzyme; she has received honoraria in this capacity and for giving lectures, which have been independently prepared. Symptoms and signs include chronic fatigue, frequent nose bleeds, prolonged bleeding or bruising, hepatomegaly, splenomegaly, skel- etal compromise, poor growth in childhood, and delayed pubertal development [ 1–3]. Skeletal compromise is observed in 70– 100% of the patients with type 1 GD, and it includes a wide range of clinical and radio- logic findings such as chronic bone pain, bone crisis, bone marrow infiltration, Erlen- meyer flask deformity, lytic lesions, osteo- sclerosis, osteonecrosis, fractures, and low bone density (measured with dual-energy x- ray absorptiometry [DEXA]) [2, 3]. The enzyme that is deficient or absent, re- sulting in GD, is replaced by an analog of the human enzyme β-glucocerebrosidase and is produced by recombinant DNA. The enzyme is administered IV every 2 weeks usually at doses N onneuropathic type 1 Gaucher disease (GD) is an autosomal-re- cessive inherited disease caused by a deficiency or absence of β-glucocerebrosidase (β-glucosidase). It can manifest at any age, but 66% of patients manifest symptoms of GD during the first 2 decades of life. The highest prevalence of type 1 GD is in Ashkenazi Jews, but it affects all ethnic groups [ 1]. The phenotype is char- acterized by painless splenohepatomegaly; infiltration of bone marrow by lysosome-en- gorged macrophages (Gaucher cells) and secondary damage to bone (osteonecrosis from bone marrow vascular compression and altered osteoclastic and osteoblastic function through defective paracrine regulation); and hypersplenism with variable low hemoglobin levels, platelet levels, and WBC counts. OBJECTIVE. The objective of our study was to use proton MR spectroscopy (MRS) to quantitatively evaluate bone marrow infiltration by measuring the fat fraction (FF) and to compare the FF with semiquantitative bone marrow MRI scores and clinical status in chil- dren treated for type 1 Gaucher disease (GD). SUBJECTS AND METHODS. Over a 2-year period, we prospectively evaluated 10 treated GD patients (six males, four females; median age, 15.1 years) and 10 healthy age- matched control subjects (five males, five females; median age, 15.3 years) using 3-T proton MRS of L5 and the femoral neck. Water and lipid AUCs were measured to calculate the FF. Two blinded pediatric musculoskeletal radiologists performed a semiquantitative analysis of the conventional MR images using the bone marrow burden score and modified Spanish MRI score. We evaluated symptoms, spleen and liver volumes, platelet levels, hemoglobin levels, and bone complications. RESULTS. In the femur, the FF was higher in the control subjects (median, 0.71) than the GD patients (0.54) ( p = 0.02). In L5, the difference in FF—higher FF in control subjects (0.37) than in GD patients (0.26)—was not significant ( p = 0.16). In both groups and both re- gions, the FF increased with patient age ( p < 0.02). Semiquantitative scores showed no dif- ferences between control subjects and treated GD patients ( p > 0.11). Eight of 10 GD patients were asymptomatic and two had chronic bone pain. The median age of patients at symptom onset was 4.0 years, the median age of patients at the initiation of enzyme replacement thera- py was 4.3 years, and the median treatment duration was 10.2 years. Hemoglobin level, plate- let count, and liver volume at MRI were normal. Mean pretreatment spleen volume (15.4-fold above normal) decreased to 2.8-fold above normal at the time of MRI ( p = 0.01). CONCLUSION. Proton MRS detected FF differences that were undetectable using con- ventional MRI; for that reason, proton MRS can be used to optimize treatment of GD patients. Jaramillo et al. Proton MRS to Quantify Bone Marrow Involvement in GD Pediatric Imaging Original Research Downloaded from www.ajronline.org by 52.73.204.196 on 05/17/22 from IP address 52.73.204.196. Copyright ARRS. 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