Preliminary Study Of The Biological Effects Of Radiation Based On GC-MS Metabolomics In Multislice Computed Tomography Coronary Artery Angiography

Part 1 Preliminary study of applying the γH2AX analysis in comparing the radiation dose and in vivo DNA double-strand breaks induced during high pitch Flash scans with prospective ECG-triggering and low-pitch spiral scans with retrospective ECG- triggeringObjectives To compare the radiation dose and in vivo DNA double-strand breaks induced during high-pitch Flash scans with prospective ECG-triggering and conventional low-pitch spiral scans with retrospective ECG-triggering as well as to evaluate the prospect of γH2AX analysis used as a sensitive biologic dosimeter of low-level X-ray radiation. Methods Forty patients underwent coronary computed tomography angiography either using Flash spiral data acquisition(n=18) whose heart rate was less than 70 bpm with sinus rhythm or low-pitch spiral data acquisition(n=22) otherwise. CARE k V and CARE Dose4 D were used in both groups. Blood samples were obtained before and 30 minutes after CT scans. Lymphocytes were isolated, stained against the phosphorylated histone variant γH2AX, and DNA double-strand breaks(DSBs) were visualized using fluorescence microscopy. The differences of gender composition between the two groups were assessed by Chi-square test. BMI, foci/cell(before) and foci/cell(after) were assessed by two independent samples t test. Difference between foci/cell(excess), CTDIvol, DLP and ED were compared by Mann-Whitney test. The differences between foci/cell(before) and foci/cell(after) in all patients was assessed by Paired t-test. Spearman correlations(r) was calculated between the DLP and CT-induced DSBs levels. Results The basic characteristics(the composition of sex, BMI) of the patients are comparable with no significant difference in two groups. The CTDIvol, DLP and ED in Flash group were significantly lower than those of low-pitch spiral group:(12.29±1.68)m Gy,(100.28±30.60)m Gy?cm,(1.41±0.43)m Sv vs(39.11±10.75)m Gy,(537.27±152.74)m Gy?cm,(7.52±2.14)m Sv. The foci/cell(before) and The foci/cell(after) in all patients was(0.137±0.036) vs(0.244±0.072), t=10.294, P<0.01. The foci/cell(excess) was lower in high-pitch Flash group(0.058±0.034)than that in low-pitch spiral group(0.148±0.058,U=27.50, P<0.01).The increase of γH2AX foci after CT depends linearly on the DLP(r=0.78, P<0.01)in low-pitch spiral group, while no correlation was found in high-pitch Flash group. Conclusions The radiation dose and in vivo DNA double-strand breaks induced during high-pitch Flash scan was significantly lower than that in low-pitch spiral scans while diagnostic image quality was obtained in both groups. Using γH2AX analysis as a sensitive biologic dosimeter when exposed to low-level radiation is highly promising. Part 2 Preliminary study of applying metabonomics based on GC-MS technology in comparing the radiation dose and its biological effects of ionizing radiation on plasma metabolites induced during high pitch Flash scans with prospective ECG-triggering and low-pitch spiral scans with retrospective electrocardiography ECG- triggeringObjectives To compare the radiation dose and investigate the biological effects of ionizing radiation on plasma after high-pitch Flash scans with prospective ECG-triggering and conventional low-pitch spiral scans with retrospective ECG-triggering as well as to evaluate the availability and prospect of radiation metabolomics used as a sensitive method in studying biological effects of low-level X-ray radiation. Methods sixty-one patients underwent coronary computed tomography angiography either using high-pitch Flash spiral data acquisition(n=24) whose heart rate was less than 70 bpm/min with sinus rhythm or low-pitch spiral data acquisition(n=37) otherwise. Blood samples were obtained 30 minutes before and after CT scans. The differences in the composition of blood lipid, blood pressure and blood glucose levels in each patient of the two group were assessed by Fisher’s Exact Test. Gender composition was assessed by Chi-square test. BMI was assessed by two independent samples t test. A GC-MS method was developed to analyse plasma metabolites.(Orthal)Partial least square-discrimination analysis(OPLS-DA) was applied for the discriminant analysis between samples before and after MSCTCA and for the screening of the potential radiation biomarkers. Finally,students’ t test was applied to compare the change of the biomarkers in the plasma before and after CT. Results The basic characteristics are comparable with no significant difference in two groups. The DLP in Flash group were significantly lower than those of in low-pitch spiral group:(93.08±29.57)m Gy?cm vs(689.70±278.10)m Gy?cm,P<0.01. An OPLS-DA model was basically established, which got a good result for recognition and prediction within samples before and after CT. In high-pitch Flash group, marked decreases in lactic acid and urea and increases in palmitic acid, Octadecanoic acid and an unknown compound were observed in samples after CT compared with samples before CT, which can also be found in low-pitch spiral group. In addition, decrease in L-Proline and increase in phosphoric acid were observed compared with Flash group. Finally,5 compounds was chosen as radiation biomarker in Flash group,while 7 compounds in low-pitch spiral group.Student’s t test supported the findings in low-pitch spiral group. Conclusions Effects on plasma metabolites induced during high-pitch Flash scan was significantly smaller than that of low-pitch spiral scan. Lactic acid and seven other small metabolites had important effect on the classification of the radiation exposure or non-exposure. Metabolomic can be an excellent method to learn biological effects of low-level radiation and it is meaningful to uncover the mechanism of the biological effects of low-level radiation as well.