Gaucher disease is a common genetic lysosomal storage disorder which results from a deficiency of the lysosomal enzyme glucocerebrosidase. Traditionally, brain was deemed as spared in patients of type Ⅰ Gaucher disease. However, a few recent work has reported that more than 36% to 49% type Ⅰ Gaucher disease patients suffering at least one neurological symptom ^1,2.Parkinson disease or parkinsonian symptoms have also been reported as an incidental association with type Ⅰ Gaucher disease recently ³. Moreover, an autopsy study has observed astrogliosis in cerebral cortical layers 3 and 5, hippocampal CA2-4, and layer 4b in type Ⅰ Gaucher disease patients ⁴. It has been suggested that Gaucher disease’s neuropathology process should be considered as a continuum phenotype, rather than a discrete predefined classification ⁵ .In this work, Diffusion Kurtosis Imaging (DKI) was used to investigate the potential morphological change in hippocampal, olfactory gyrus, calcarine and substania nigra of type Ⅰ Gaucher disease patients, according to the previous findings ^4,6 .

38 type Ⅰ Gaucher disease children patients and 32 normal children were recruited in this study, with the approve of local IRB. All normal children had no history of neurological or psychiatric illness. MR images were scanned using a 3T Philips Achieva TX scanner. High-resolution anatomical images were acquired using a three-dimensional gradient echo sequence with following parameters: Whole brain coverage, TE/TR =3.8/8.3 ms, FA = 12, slice thickness of 1mm, matrix size = 180×180, FOV=180×200×160. Diffusion Kurtosis images were acquired using a single shot echo planar imaging applied in 15 non-collinear directions and a b-value of 0,1000,2000 s/mm2: TR = 8760 ms, TE = 92 ms, field of view = 224 mm × 224 mm, acquisition matrix = 112 × 112, 70 slices were acquired with a slice thickness of 2.0 mm and no gap.

MD and MK maps were calculated by using the Diffusional Kurtosis Estimator (DKE) (www.nitrc.org/projects/dke). Regions of interest (ROIs) of bilateral olfactory gyrus , calcarine , hippocampus and substania nigra were determined by ALL and TD brodmann areas template. T test was used to detect the group difference of MD and MK value between type Ⅰ Gaucher disease patients and controls. Statistical significance level of P＜0.05 was considered as significant.

Compared with healthy controls, significant decrease of MD in type Ⅰ Gaucher disease patients was found in the bilateral olfactory gyrus and increases in right calcarine and substantia nigra. Significant increase of MK in type Ⅰ Gaucher disease patients was found in the right olfactory gyrus. The MD and MK changes in olfactory are relevant to maybe the astrogliosis ⁷ and these changes are compatible with a previous study which reported that patients with Gaucher disease had the significantly lower olfactory function scores than controls ^6. The MD changes in right calcarine and substantia nigra are compatible with the previous autopsy study, may be relevant to the neuronal loss.This preliminary study provides novel evidences for structural abnormalities in type Ⅰ Gaucher disease patients, suggesting a necessity of adjusting the opinion regarding the CNS-involvement of type Ⅰ Gaucher disease. Our findings also suggest that DKI analysis is a potential imaging marker to monitor the brain change in type Ⅰ Gaucher disease.