NC-13CRANIAL RADIATION ENCOMPASSING THE GENU IS ASSOCIATED WITH NEURO-PSYCHOLOGICAL SEQUELAE IN CHILDREN: A PROSPECTIVE STUDY OF DIFFUSION TENSOR IMAGING (DTI) AND PROTON MR SPECTROSCOPY (MRS)

摘要

PURPOSE: This study examines white matter integrity as measured by DTI and proton MR spectroscopy (MRS) and their associations with region specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. METHODS: 20 patients and 34 age-& sex-matched controls participated. MRS and DTI and neuropsychological assessment were conducted at baseline, 6, 15, 27 months (times 1-4) following RT and compared to a single visit in controls. Neuro-psychological battery included: motor dexterity, visual attention/processing speed, visual and verbal working memory. White matter regions contoured and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each. Concentrations of neuro-metabolites were expressed as ratios N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr. Linear mixed effects (LME) regression models were used to examine associations among ADC, FA, metabolite ratios, RT dose to contoured structures, and performance on testing, and to compare findings for patients versus controls. RESULTS: Mean prescription dose: 44.2 Gy (range 2-59.4 Gy). LME analyses demonstrated significant differences between patients and controls in NAA/Cr and ADC, with the greatest difference at time 4 (p = <0.01 and <0.0001, respectively). At time 4, the ADC difference was most significant in the temporal lobes (p < 0.0001), genu (p = 0.01) and splenium (p = 0.01). Increasing radiation dose was associated with an increase in ADC at time 3 (p = 0.005), with the most pronounced effects in the genu. There was no significant difference in RT dose to the genu versus splenium. Overall, there was poorer performance on visual working memory with higher ADC in the genu, especially in patients (group by ADC, p = 0.02) and a trend towards poorer performance on motor dexterity with higher ADC in the genu in patients at baseline (p = 0.057). CONCLUSIONS: The genu is a region with increased susceptibility to injury associated with neuro-psychological sequelae. Efforts should be made to limit radiation dose to this region during treatment planning.