Experimental examination of radiation doses from cardiac and liver CT perfusion in a phantom study as a function of organ, age and sex.

Cardiac and liver computed tomography (CT) perfusion has not been routinely implemented in the clinic and requires high radiation doses. The purpose of this study is to examine the radiation exposure and technical settings for cardiac and liver CT perfusion scans at different CT scanners. Two cardiac and three liver CT perfusion protocols were examined with the N1 LUNGMAN phantom at three multi-slice CT scanners: a single-source (I) and second- (II) and third-generation (III) dual-source CT scanners. Radiation doses were reported for the CT dose index (CTDIvol) and dose-length product (DLP) and a standardised DLP (DLP10cm) for cardiac and liver perfusion. The effective dose (ED10cm) for a standardised scan length of 10 cm was estimated using conversion factors based on the International Commission on Radiological Protection (ICRP) 110 phantoms and tissue-weighting factors from ICRP 103. The proposed total lifetime attributable risk of developing cancer was determined as a function of organ, age and sex for adults. Radiation exposure for CTDIvol, DLP/DLP10 cmand ED10 cmduring CT perfusion was distributed as follows: for cardiac perfusion (II) 144 mGy, 1036 mGy·cm/1440 mGy·cm and 39 mSv, and (III) 28 mGy, 295 mGy·cm/279 mGy·cm and 8 mSv; for liver perfusion (I) 225 mGy, 3360 mGy·cm/2249 mGy·cm and 54 mSv, (II) 94 mGy, 1451 mGy·cm/937 mGy·cm and 22 mSv, and (III) 74 mGy, 1096 mGy·cm/739 mGy·cm and 18 mSv. The third-generation dual-source CT scanner applied the lowest doses. Proposed total lifetime attributable risk increased with decreasing age. Even though CT perfusion is a high-dose examination, we observed that new-generation CT scanners could achieve lower doses. There is a strong impact of organ, age and sex on lifetime attributable risk. Further investigations of the feasibility of these perfusion scans are required for clinical implementation.

Experimental Examination of Conventional, Semi-Automatic, and Automatic Volumetry Tools for Segmentation of Pulmonary Nodules in a Phantom Study.

The aim of this study is to examine the precision of semi-automatic, conventional and automatic volumetry tools for pulmonary nodules in chest CT with phantom N1 LUNGMAN. The phantom is a life-size anatomical chest model with pulmonary nodules representing solid and subsolid metastases. Gross tumor volumes (GTVis) were contoured using various approaches: manually (0); as a means of semi-automated, conventional contouring with (I) adaptive-brush function; (II) flood-fill function; and (III) image-thresholding function. Furthermore, a deep-learning algorithm for automatic contouring was applied (IV). An intermodality comparison of the above-mentioned strategies for contouring GTVis was performed. For the mean GTVref (standard deviation (SD)), the interquartile range (IQR)) was 0.68 mL (0.33; 0.34-1.1). GTV segmentation was distributed as follows: (I) 0.61 mL (0.27; 0.36-0.92); (II) 0.41 mL (0.28; 0.23-0.63); (III) 0.65 mL (0.35; 0.32-0.90); and (IV) 0.61 mL (0.29; 0.33-0.95). GTVref was found to be significantly correlated with GTVis (I) p < 0.001, r = 0.989 (III) p = 0.001, r = 0.916, and (IV) p < 0.001, r = 0.986, but not with (II) p = 0.091, r = 0.595. The Sørensen-Dice indices for the semi-automatic tools were 0.74 (I), 0.57 (II) and 0.71 (III). For the semi-automatic, conventional segmentation tools evaluated, the adaptive-brush function (I) performed closest to the reference standard (0). The automatic deep learning tool (IV) showed high performance for auto-segmentation and was close to the reference standard. For high precision radiation therapy, visual control, and, where necessary, manual correction, are mandatory for all evaluated tools.

EXPERIMENTAL EXAMINATION OF RADIATION DOSES OF DUAL- AND SINGLE-ENERGY COMPUTED TOMOGRAPHY IN CHEST AND UPPER ABDOMEN IN A PHANTOM STUDY.

The aim of this phantom study is to examine radiation doses of dual- and single-energy computed tomography (DECT and SECT) in the chest and upper abdomen for three different multi-slice CT scanners. A total of 34 CT protocols were examined with the phantom N1 LUNGMAN. Four different CT examination types of different anatomic regions were performed both in single- and dual-energy technique: chest, aorta, pulmonary arteries for suspected pulmonary embolism and liver. Radiation doses were examined for the CT dose index CTDIvol and dose-length product (DLP). Radiation doses of DECT were significantly higher than doses for SECT. In terms of CTDIvol, radiation doses were 1.1-3.2 times higher, and in terms of DLP, these were 1.1-3.8 times higher for DECT compared with SECT. The third-generation dual-source CT applied the lowest dose in 7 of 15 different examination types of different anatomic regions.

Blockade of the PDGFR family together with SRC leads to diminished proliferation of colorectal cancer cells.

Among the family of receptor tyrosine kinases (RTKs), platelet-derived growth factor receptor (PDGFR) has attracted increasing attention as a potential target of anti-tumor therapy in colorectal cancer (CRC). To study the function of PDGFRß in CRC cell lines, SW480, DLD-1 and Caco-2 cells showing high PDGFRß expression were used for receptor down-regulation by small interfering RNA (siRNA) and using the pharmacological inhibitor of PDGFRß Ki11502. Blockade of PDGFRß using both approaches led to moderate inhibition of proliferation and diminished activation of the downstream PI3K-signaling pathway in all three cell lines. Surprisingly, incubation with Ki11502 resulted in an arrest of SW480 cells in the G2 phase of the cell cycle, whereas the siRNA approach did not result in this effect. To address this difference, we analyzed the involvement of the PDGFRß family member c-KIT in Ki11502 effectiveness, but siRNA and proliferation studies in SW480 and DLD-1 cells could not prove the involvement of c-KIT inactivation during Ki11502 treatment. Hence, an RTK activation antibody array on SW480 cells led us to the identification of the non-receptor tyrosine kinase SRC, which is inactivated after Ki11502 treatment but not after the siRNA approach. Further studies using the SRC-specific inhibitor PP2 showed that SRC inhibition upon treatment with the inhibitor Ki11502 is responsible for the observed effects of Ki11502 in SW480 and DLD-1 CRC cells. In summary, our results demonstrate that the inhibition of PDGFRß alone using siRNA has only moderate cellular effects in CRC cell lines; however, the multi-target inhibition of PDGFRß, c-KIT and SRC, e.g., using Ki11502, represents a promising therapeutic intervention for the treatment of CRC.