Influence of risk-organ-based tube current modulation on CT-induced DNA double-strand breaks in a biological phantom model

Abstract

Techniques for dose reduction in computed tomography (CT) are receiving increasing attention. Lowering the tube current in front of the patient, known as risk-organ-based tube current modulation (RTM), represents a new approach. Physical dose parameters can determine the exposure but are not able to assess the biological-X-ray interactions. The purpose of this study was to establish a biological phantom model to evaluate the effect of RTM on X-ray-induced DNA double-strand breaks (DSBs). In breast phantoms and in the location of the spine in an Alderson phantom, isolated human blood lymphocytes were irradiated using a 128-slice CT scanner. A standard thoracic CT protocol (120 kV, 110 ref. mAs, anatomy-based tube current modulation, pitch 0.6, scan length 30 cm) with and without RTM was used. X-ray-induced DSBs were quantified in isolated blood lymphocytes using immunofluorescence microscopy after staining for the phosphorylated histone variant γ-H2AX. Using RTM, the resulting DNA damage reduction was 41% in superficial breast locations (P = 0.0001), 28% in middle breast locations (P = 0.0003) and 29% in lower breast locations (P = 0.0001), but we found a DNA damage increase of 36% in superficial spine locations (P = 0.0001) and of 26% in deep spine locations (P = 0.0001). In summary, we established a biological phantom model that is suitable for detecting DNA damage in distinct organs. In addition, we were able to show that, using RTM, X-ray-induced DNA damage in the breast can be significantly reduced; however, there is a significant increase in DSBs in the location of the spine.

Fig. 1.

Set-up for in vitro testing: On the left panel of Fig. 1a, the Alderson chest phantom and the three slices of the breast phantoms are shown. The Alderson Phantom was placed in the center of the CT-scanner, and the breast phantoms were positioned on the chest. The right panel demonstrates the locations of the lymphocyte samples in the different boreholes for the distinct slices of the breast essays. For each experiment, we placed four lymphocytes samples in the superficial slice (Numbers 1–4), two in the middle slice (Numbers 5–6) and four in the deep slice (Numbers 7–10) in various locations. In Fig. 1b, the spinal sample locations are shown. Two samples were placed in three consecutive slices corresponding to the breast phantoms (deep locations: R1, R3, R5; superficial locations: R2, R4, R6).

Fig. 2.

Set-up for establishment of the phantom model using the CTDI phantom: a standard chest CT protocol with a constant tube voltage of 120 kV and various tube current time products without anatomy-based or risk-organ–based tube current modulation. The x-axis shows the tube current time product, the y-axis represent the excess foci levels. The Pearson correlation (r), both for the peripheral (squares) and the central locations (circles) are shown. The figure illustrates the mean excess foci of three independent measurements. A P-value <0.05 was considered statistically significant.

Fig. 3.

Excess foci in all of the distinct tested sample locations in the Alderson phantom: (a) shows the values of the breast phantoms, locations correspond to the locations of Fig. 1a; (b) demonstrates values in the spine locations in three consecutive slices of the chest phantom (R1, R3 and R5: deep position; R2, R4 and R6: superficial position). The black columns show samples irradiated using the standard protocol without RTM; the grey columns indicate samples irradiated using RTM. Columns represent mean excess foci; error bars indicate standard deviation.

Fig. 4.

Dependency of excess foci on the sample locations in the phantom: Part (a) shows mean excess foci of samples placed in the superficial, middle and deep slices of the breast phantoms, and in the superficial and deep spine locations in the chest phantom. Means (columns) and standard deviation (error bars) of each slice are presented. Part (b) shows the percentage of DSB reduction/elevation in RTM in comparison with the standard thoracic protocol. For this illustration, the values of the samples irradiated without RTM, as shown in panel (a), were considered to be 100%. The black columns show samples irradiated using the standard protocol without RTM; the grey columns indicate samples irradiated using RTM.