title: Dixon quantitative chemical shift imaging is a sensitive tool for the evaluation of bone marrow responses to individualized doses of enzyme supplementation therapy in type 1 Gaucher disease.
abstract: Type 1 Gaucher disease can be effectively treated with enzyme supplementation therapy. Bone disease is a debilitating feature of the disorder and results from infiltration of the bone marrow by Gaucher cells. The effect of treatment on bone marrow infiltration is difficult to measure, necessitating the development of sensitive techniques to allow adequate dosing. Dixon quantitative chemical shift imaging (Dixon-QCSI) is a MRI technique to measure displacement of fatty marrow by Gaucher cells. Low bone marrow fat fractions have been found in Gaucher disease. We studied the effect of individualized low doses of enzyme therapy on the fat fractions of the lumbar spine in 12 adult Gaucher disease patients before and during treatment and in 9 untreated Gaucher controls. Fat fractions were decreased in 9/12 patients (median 0.20, range 0.08-0.40) and equally low in the untreated Gaucher controls compared to age-matched healthy volunteers (normal values 0.27-0.43, P < 0.01). During treatment, fat fractions increased significantly already after 1 year in 11/12 patients (P = 0.007). After 4 to 5 years, fat fractions normalized in 11/12 patients. Fat fractions remained low in the untreated Gaucher controls (P = 0.5 and 0.6 at 1 and 2 years, respectively). Six of 11 patients had a dose increase, which did not clearly affect fat fractions. Dixon-QCSI is a sensitive tool for the measurement of the response of bone marrow to enzyme therapy.
authors.affiliation: Department of Hematology, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. c.e.hollak@amc.uva.nl
authors.forename: C
authors.initials: C
authors.lastname: Hollak
authors.forename: M
authors.initials: M
authors.lastname: Maas
authors.forename: E
authors.initials: E
authors.lastname: Akkerman
authors.forename: A
authors.initials: A
authors.lastname: den Heeten
authors.forename: H
authors.initials: H
authors.lastname: Aerts
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005962:Glucosylceramidase / Q000008:administration & dosage*; D006801:Humans; D008137:Longitudinal Studies; D008161:Lumbosacral Region / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; C070292:alglucerase; D005962:Glucosylceramidase; C090568:imiglucerase