Intra-scanner repeatability of quantitative imaging features in a 3D printed semi-anthropomorphic CT phantom.

OBJECTIVES: Radiomics has shown to provide novel diagnostic and predictive disease information based on quantitative image features in study settings. However, limited data yielded contradictory results and important questions regarding the validity of the methods remain to be answered. The purpose of this study was to evaluate how clinical imaging techniques affect the stability of radiomics features by using 3D printed anthropomorphic CT phantom to test for repeatability and reproducibility of quantitative parameters. METHODS: 48 PET/CT validated lymph nodes of prostate cancer patients (24 metastatic, 24 non-metastatic) were used as a template to create a customized 3D printed anthropomorphic phantom. We subsequently scanned the phantom five times with a routine abdominal CT protocol. Images were reconstructed using iterative reconstruction and two soft tissue kernels and one bone kernel. Radiomics features were extracted and assessed for repeatability and susceptibility towards image reconstruction settings using concordance correlation coefficients. RESULTS: Our analysis revealed 19 of 86 features (22 %) as highly repeatable (CCC ≥ 0.85) with low susceptibility towards image reconstruction protocols. Most features analyzed depicted critical non-repeatability with CCC's < 0.75 even under entirely consistent imaging acquisition settings. Edge enhancing kernels result in higher variances between the scans and differences in repeatability and reproducibility were detected between PSMA-positive and negative lymph nodes with overall more stable features seen in tumor positive lymph nodes. CONCLUSIONS: Both, repeatability and reproducibility play a crucial role in the validation process of radiomics features in clinical routine. This phantom study shows that most radiomics features in contrast to previous studies, including phantom and clinical, do not depict sufficient intra-scanner repeatability to serve as reliable diagnostic tools.

Split-bolus vs. multiphasic contrast bolus protocol in patients with pancreatic cancer or cholangiocarcinoma.

PURPOSE: To investigate the image quality, diagnostic accuracy, and dose reduction potential of a split-bolus protocol(SBP) compared with a multiphasic protocol(MPP) in the detection of recurrent or progressive pancreatic ductal adenocarcinoma(PDAC) or cholangiocarcinoma(CC) using contrast- enhanced computed tomography(CECT). MATERIALS AND METHODS: This prospective study included 56 patients who underwent CECT, 28 with our institutional standard MPP(100 ml contrast bolus) and 28 with a novel SBP(110 ml). Radiation exposure was determined in terms of total dose- length product(DLP) and computed tomography dose index(CTDI). Image quality was measured objectively by analysis of attenuation in Hounsfield units(HU) in regions of interest(ROIs) and subjectively by two blinded readers using a Likert scale. Diagnostic accuracy and interreader variability were tested. RESULTS: The total DLP of the SBP group(498.1 ± 43.7 mGy*cm) was significantly lower than in the MPP group(1,092.5 ± 106.9 mGy*cm; p < 0.001). The SBP showed higher contrast enhancement of all critical anatomical structures including portal vein, liver, and pancreas compared with the MPP, except for the aorta(SBP: 326.9 ± 15.7 HU vs. MPP: 246.7 ± 12.2 HU; p < 0.001). Subjective analysis revealed poorer image quality ratings for important landmarks with the MPP (resection surface: p = 0.624, portal vein: p = 0.395, liver p = 0.361). The two blinded readers correlated significantly. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and overall interreader variabilities correlated significantly. Furthermore, significantly fewer slices per exam were required for the SBP(1,823 vs. 3,235; p < 0.001). CONCLUSION: The SBP provides the same image quality and diagnostic accuracy as an MPP while significantly lowering radiation exposure in CT follow-up of PDAC or CC.

Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice.

UNLABELLED: Salinomycin is a polyether antibiotic which effectively eliminates a variety of cancer stem cells and chemotherapy-resistant tumor cells in vitro and in vivo. One important caveat for its clinical application is the paucity of preclinical pharmacological and safety data. In the present study, we thus aimed to elucidate pharmacokinetic properties of salinomycin and to assess the side effect profile of chronic treatment with this compound in C57Bl/6 mice. In addition, we tested whether neurotoxic side effects can be prevented by interference with the intracellular calcium homeostasis. We observed that salinomycin has a narrow therapeutic index; however, a dose of 5 mg/kg body weight was well tolerated, and analysis of blood parameters as well as organ histology of liver, kidney, skeletal muscle, and heart showed no abnormalities after daily salinomycin injection for 4 weeks. Pharmacokinetic evaluation revealed low micromolar peak concentrations and an almost complete systemic elimination within 5 h after injection. In contrast to low systemic toxicity, typical signs of a sensory polyneuropathy with mechanical and cold allodynia, distinct gait alterations, decreased sensory nerve action potential amplitudes, and loss of myelinated fibers in the sciatic nerve were observed in salinomycin-treated animals. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger partially prevented the development of salinomycin-induced neuropathy in vivo, an approach which did not reduce salinomycin's antineoplastic efficacy in vitro. Taken together, this study establishes a framework of pharmacokinetic data for future preclinical trials and safety data for translational trials. Furthermore, we established a strategy to reduce salinomycin's off-target neurotoxic effects. KEY MESSAGE: Salinomycin has a narrow therapeutic index; a dose of 5 mg/kg is tolerated in mice. Mice treated with salinomycin develop a painful sensory polyneuropathy. An optimized protocol was established to measure salinomycin in serum samples. Inhibition of Na(+)/Ca(2+) exchangers prevents salinomycin-induced neuropathy. Blocking mitochondrial Na(+)/Ca(2+) exchangers does not impair antineoplastic efficacy.