Bone Marrow MRI And MRS Study After Administration Of RhG-CSF In Cynomolgus Monkey

Purpose:To assess the time course and extension of lumbar and proximal femoral marrow conversion and reconversion after short-term stimulation by rhG-CSF in healthy adult Cynomolgus monkey using magnetic resonance imaging(MRI)and magnetic resonance spectroscopy(MRS)?Materials and Methods:13 cynomolgus monkeys were selected(9-13 years)in this study and underwent MRI and MRS in penultimate lumbar vertebral body.MRS was acquired with SV-PRESS.MRI/MRS examination and peripheral blood counting were performed in each cynomolgus monkeys in days before subcutaneous injection of rhG-CSF for comparison and in days after the injection of rhG-CSF at 2,4,6,8,10,12,14,16,18,20,25,30,45,60 days for study respectively.The ratio of areas under the water-and fat-specific peaks(W/F)in MRS,the index of the vertebral body fat(FI),contrast noise ratio(CNR)in MRI,peripheral white blood cell(WBC)count and ratio of CD34 + cell at different times were calculated in order to study the variation tendency and variation correlations statistically.Finally,the posterior superior iliac biopsy and bone marrow aspiration was performed to validate the accuracy of the MRS.Self-control experimental designs and repeated measures analysis of variance and correlation analysis used in this study.Results:MRI and MRS of bone marrow before rhG-CSF injection were used as a comparison control group:vertebral central zone of high signal intensity(fatty marrow)seen on T1WI,the W/F ratio was 1.73 ± 0.57.The proximal femoral shows the uniform high signal intensity of a marrow space completely.The vertebral body marrow of central high signal intensity compared with the previous gradually reduce or disappear at 2--8th days after injection of rhG-CSF,but the W/F ratio gradually increased and reached its maximum at 8th day,with the W/F ratio was 6.83±3.57.The peak of the lumbar bone marrow reconversion found at 8th day.There is a small amount of high signal returning to the center of the vertebral body and the signal intensity gradually increasing at 10--30th day after injection of rhG-CSF.The water-and fat-specific peaks reversed of marrow which stand for the W/F ratio declined in MR spectroscopy tended to be rapid at 8--14th day(4.04± 1.17 at 14th day),and remained at 14--25th day(approximately 3.45 ± 0.93).Two months later,the vertebral high signal intensity seen on T1WI was nearly reconvered almost the same to control group.The W/F ratio at 30th,45th and 60th day after injection of rhG-CSF was 3.30±0.11,2.60±0.61and 1.54±0.35 respectively.The results indicated the course of lumbar bone marrow reconversion and recover mechanic.The course of fat composition disappeared and recovered in proximal femur bone marrow in MRI delay about 2 to 4 days compared to vertebral marrow.Marrow convered and reconvered trends found in MRI were observed corresponding the W/F ratio,peripheral blood count of WBC and CD34+ and iliac marrow aspiration before and after rhG-CSF injection.Conclusion:1.Cynomolgus monkey WBC and CD34 + significantly rose to the peak at 4th day after rhG-CSF administration,and return to near pre-injection level at 4-8th day after rhG-CSF administration.The W/F ratio in MRS significantly rose to its maximum level at 8th day after rhG-CSF administration,and returned to half of the peak at 8—14th day,then showed a slow recovery at 14--60th day,returned to pre-injection level approximately at 60th day.Marrow composition of red-to-yellow convered and reconvered trends found in MRI were observed corresponding the W/F ratio in MRS.2?MRI and MRS provides valuable information about altered bone marrow composition,in addition,confirmed by bone marrow aspiration.The changes of peripheral WBC and CD34 + fasted rising and falling were earlier about 4 days than the changes of bone marrow composition.The characteristics of bone marrow composition changes in the cynomolgus monkey,which can provide reference values for the study of human bone marrow.