Correlation of MRI-Based bone marrow burden score with genotype and spleen status in Gaucher's disease

Abstract

Objective: The purpose of this study was to correlate skeletal pathologic findings quantified by MRI-based bone marrow burden score with genotype and spleen status and other clinical parameters, including liver size and duration of enzyme replacement therapy, in patients with Gaucher's disease.

Materials and methods: Two radiologists retrospectively reviewed MR images of 47 patients with Gaucher's disease and determined bone marrow burden scores by consensus on the basis of previously published criteria. The bone marrow burden scores were correlated with genotype, liver volume, spleen status, age, and cumulative duration of enzyme replacement therapy.

Results: Subjects with compound heterozygous N370S alleles had significantly higher overall, lumbar spinal, and femoral bone marrow burden scores than did N370S homozygotes. There was a significant positive correlation between an enlarged or surgically absent spleen and bone marrow burden score. There were no significant associations between bone marrow burden score and liver volume, age, cumulative duration of enzyme replacement therapy, or cumulative duration of untreated disease. Femoral and lumbar spinal bone marrow burden scores had a weak but significant positive correlation across all patients.

Conclusion: Skeletal pathologic findings in Gaucher's disease encapsulated as bone marrow burden score correlate significantly with the number of copies of the N370S allele, which has an ameliorative effect on bone marrow disease. Splenectomy or splenomegaly is associated with greater risk of bone marrow disease. Femoral and lumbar spinal bone marrow burden scores, although only weakly correlated, independently illustrated both the protective role of the N370S allele and the unfavourable implication of splenectomy. This finding suggests that axial and appendicular bone marrow burdens are related but distinct and justifies multiple-compartment evaluation in Gaucher's disease.

Fig. 1

28-year-old woman with Gaucher's disease. Sagittal T1-weighted MR image shows normal bone marrow signal intensity is high in relation to nondiseased intervertebral disk signal intensity. Findings on STIR image (not shown) also were normal. Bone marrow burden score is 0.

Fig. 2

32-year-old woman with Gaucher's disease. Sagittal T1-weighted MR image shows patchy bone marrow infiltration, which is hypointense in relation to nondiseased intervertebral disk signal intensity with preservation of fat around basivertebral vein. Findings on STIR image were normal (not shown). Bone marrow burden score is 4 (3 for intensity, 1 for distribution).

Fig. 3

55-year-old woman with Gaucher's disease. Sagittal T1-weighted MR image shows slightly hypointense bone marrow signal in diffuse distribution with absence of fat around basivertebral vein. Findings on STIR image were normal (not shown). Bone marrow burden score is 5 (2 for intensity, 3 for distribution).

Fig. 4

49-year-old man with Gaucher's disease. A and B, Sagittal T1 -weighted (A) and STIR (B) MR images show bone marrow infiltration, infarction, and fractures. Patchy area of low signal intensity is evident in A, as are absence of fat around basivertebral vein and high signal intensity in B. Bone marrow burden score is 7 (5 for intensity, 2 for distribution).

Fig. 5

41-year-old man with Gaucher's disease. A and B, Coronal T1-weighted (A) and STIR (B) MR images show minimal bone marrow infiltration with slightly low (A) and slightly high (B) signal intensity in both femurs with diaphyseal distribution. Bone marrow burden score is 3 (2 for intensity, 1 for distribution).

Fig. 6

70-year-old man with Gaucher's disease. A and B, Coronal T1-weighted (A) and STIR (B) MR images show low (A) and high (B) signal intensity in diaphyseal distribution in right femur. Bone marrow burden score is 5 (4 for intensity, 1 for distribution).

Fig. 7

41-year-old woman with Gaucher's disease. A and B, Coronal T1-weighted (A) and STIR (B) MR images show low (A) and high (B) signal intensity in diaphyseal distribution in left femur. Bone marrow burden score is 6 (5 for intensity, 1 for distribution).

Fig. 8

Graph shows relation between bone marrow burden and genotype. White indicates lumbarspine; gray, femurs; black, overall.

Fig. 9

Graph shows relation between bone marrow burden and genotype for patients with homozygous (white) and those with heterozygous (black) N370S allele.

Fig. 10

— 29-year-old woman with Gaucher's disease. A , Coronal T1-weighted MR image of lower part of femurs shows low signal intensity in right distal femoral epiphysis consistent with infarction. B , Coronal T1-weighted MR image of upper part of femurs shows normal signal intensity in proximal femoral epiphyses. Pattern deviates from characteristic progression of bone marrow pathologic changes in Gaucher's disease, in which proximal femoral epiphyseal involvement precedes distal epiphyseal involvement.