MRI study of bone marrow microvascular permeability and fat content after X - ray total body irradiation

Abstract

Objective To investigate the relationship between microvascular permeability, contents of adipose and fatty acids as shown by quantitative permeability parameters of dynamic contrast- enhanced MRI (DCE-MRI) and ex vivo 1H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HRMAS NMRS) in femoral bone marrow of rats after total body irradiation (TBI) by X- ray. Methods Thirty-six 6-to- 8-week-old SD rats were randomly divided into the TBI group and control group (n=18 each). The TBI group rats received 6.0 Gy high energy X-ray TBI, whereas the control rats did not receive any irradiation. Before irradiation and on days 4 and 7 after irradiation, femur DCE - MRI perfusion imaging was used to measure the volume transfer constant (Ktrans) , reflux rate constant (kep) , plasma volume fraction (vp) and extravascular extracellular volume fraction (ve) of microvessels in femoral region of interest (ROI). The rat bone marrow tissue was frozen with liquid nitrogen and then examined with 1H HRMAS NMRS. The adipose content and microvessel density (MVD) in the bone marrow were studied pathologically. Results Across all time points before and after X- ray irradiation, the TBI group showed significant changes in DCE- MRI perfusion parameters Ktrans, kep, vp and ve, the Ktrans value was increasing until peaking on day 7 after irradiation; the vp value appeared serially decreasing (all P<0.01) ; the kep value was reduced to 0.360 ±0.049/min (P<0.01) on day 4 and to 0.689 ± 0.138/min on day 7 (P<0.01) after irradiation; the ve value increased to 3.331±0.817 on day 7 (P<0.01) , and remained unchanged on day 7 after irradiation (P=0.355). Across all time points before and after X- ray irradiation, the TBI group also showed significant changes in proportions of (n-3) poly-unsaturated fatty acids (PUFA) , (n-6) PUFA and saturated fatty acids (SAFA) in femoral bone marrow. After irradiation, the proportion of bone marrow (n-6) PUFA gradually increased until reaching the maximum on day 7, while the proportion of bone marrow (n-3) PUFA gradually decreased (all P<0.01). At all time points in the TBI rats, the Ktrans value was negatively correlated with (n-3) PUFA (r=-0.639 3, P<0.01) , and positively correlated with (n-6) PUFA (r=0.684 1, P<0.05) of the bone marrow. Conclusion Bone marrow microcirculation and microvascular permeability may be correlated with adipose content after TBI. The changes in bone marrow microcirculation may be underlain by a pathophysiology mechanism based on fat-vascular permeability. Key words: Dose-response relationship, radiation; Bone marrow; Fat; Magnetic resonance imaging; Magnetic resonance spectroscopy