XDose: toward online cross-validation of experimental and computational X-ray dose estimation.

PURPOSE: As the spectrum of X-ray procedures has increased both for diagnostic and for interventional cases, more attention is paid to X-ray dose management. While the medical benefit to the patient outweighs the risk of radiation injuries in almost all cases, reproducible studies on organ dose values help to plan preventive measures helping both patient as well as staff. Dose studies are either carried out retrospectively, experimentally using anthropomorphic phantoms, or computationally. When performed experimentally, it is helpful to combine them with simulations validating the measurements. In this paper, we show how such a dose simulation method, carried out together with actual X-ray experiments, can be realized to obtain reliable organ dose values efficiently. METHODS: A Monte Carlo simulation technique was developed combining down-sampling and super-resolution techniques for accelerated processing accompanying X-ray dose measurements. The target volume is down-sampled using the statistical mode first. The estimated dose distribution is then up-sampled using guided filtering and the high-resolution target volume as guidance image. Second, we present a comparison of dose estimates calculated with our Monte Carlo code experimentally obtained values for an anthropomorphic phantom using metal oxide semiconductor field effect transistor dosimeters. RESULTS: We reconstructed high-resolution dose distributions from coarse ones (down-sampling factor 2 to 16) with error rates ranging from 1.62 % to 4.91 %. Using down-sampled target volumes further reduced the computation time by 30 % to 60 %. Comparison of measured results to simulated dose values demonstrated high agreement with an average percentage error of under [Formula: see text] for all measurement points. CONCLUSIONS: Our results indicate that Monte Carlo methods can be accelerated hardware-independently and still yield reliable results. This facilitates empirical dose studies that make use of online Monte Carlo simulations to easily cross-validate dose estimates on-site.

Pitfalls in interventional X-ray organ dose assessment-combined experimental and computational phantom study: application to prostatic artery embolization.

PURPOSE: With X-ray radiation protection and dose management constantly gaining interest in interventional radiology, novel procedures often undergo prospective dose studies using anthropomorphic phantoms to determine expected reference organ-equivalent dose values. Due to inherent uncertainties, such as impact of exact patient positioning, generalized geometry of the phantoms, limited dosimeter positioning options, and composition of tissue-equivalent materials, these dose values might not allow for patient-specific risk assessment. Therefore, first the aim of this study is to quantify the influence of these parameters on local X-ray dose to evaluate their relevance in the assessment of patient-specific organ doses. Second, this knowledge further enables validating a simulation approach, which allows employing physiological material models and patient-specific geometries. METHODS: Phantom dosimetry experiments using MOSFET dosimeters were conducted reproducing imaging scenarios in prostatic arterial embolization (PAE). Associated organ-equivalent dose of prostate, bladder, colon, and skin was determined. Dose deviation induced by possible small displacements of the patient was reproduced by moving the X-ray source. Dose deviation induced by geometric and material differences was investigated by analyzing two different commonly used phantoms. We reconstructed the experiments using Monte Carlo (MC) simulations, a reference male geometry, and different material properties to validate simulations and experiments against each other. RESULTS: Overall, MC-simulated organ dose values are in accordance with the measured ones for the majority of cases. Marginal displacements of X-ray source relative to the phantoms lead to deviations of 6-135% in organ dose values, while skin dose remains relatively constant. Regarding the impact of phantom material composition, underestimation of internal organ dose values by 12-20% is prevalent in all simulated phantoms. Skin dose, however, can be estimated with low deviation of 1-8% at least for two materials. CONCLUSIONS: Prospective reference dose studies might not extend to precise patient-specific dose assessment. Therefore, online organ dose assessment tools, based on advanced patient modeling and MC methods, are desirable.

Characterization of a new renal cell carcinoma bone metastasis mouse model.

Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently and becomes more and more prevalent presumably because survival times among patients with disseminated cancers are increasing. Patients with bone metastases from renal cell carcinoma suffer from severe pain, nerve compression syndromes and pathologic fractures. Very little is known about the mechanisms of skeletal metastases of RCC. Thus, to better understand the molecular mechanism of renal cell cancer (RCC) bone metastasis, it is crucial to develop new animal models. We have established a new animal model of RCC metastasis to bone by inoculation of human 786-O/luciferase cells into the left cardiac ventricle of athymic nude mice. The animals developed aggressive osteolytic bone destruction as monitored by radiography and micro-CT-scans with the mean endpoint at 62 +/- 8 days. The extensive bone destruction observed was comparable to the clinical setting and mainly occurred in hind limbs, forelimbs and the spine. The tumors were primarily located within the bone and resulted in destruction of cortical bone. No soft tissue metastases were detected by BLI or histomorphometry. To increase the bone-metastatic potential of the 786-O cell line, an in vivo selection was done yielding a subpopulation causing osteolytic lesions with the mean endpoint of 47 +/- 3 days. The selected subline secreted more proangiogenic factors VEGF and bFGF in vitro compared to the parental cell line suggesting that these tumors are highly vascular. This model provides a reliable reproduction of the clinical situation and therefore, is suitable for designing and evaluating more effective treatments for RCC bone metastasis.

Sagopilone inhibits breast cancer bone metastasis and bone destruction due to simultaneous inhibition of both tumor growth and bone resorption.

PURPOSE: Bone metastases have a considerable impact on quality of life in patients with breast and other cancers. Tumors produce osteoclast-activating factors, whereas bone resorption promotes the growth of tumor cells, thus leading to a "vicious cycle" of bone metastasis. Sagopilone, a novel, fully synthetic epothilone, inhibits the growth of breast cancer cells in vitro and in vivo, and here we report its activity in the MDA-MB-231(SA) breast cancer bone metastasis mouse model. EXPERIMENTAL DESIGN: The potency of sagopilone was determined in treatment models simulating the adjuvant (preventive) and metastatic (therapeutic) settings in the clinic. RESULTS: We showed that sagopilone inhibited tumor burden and bone destruction, in addition to reducing tumor-induced cachexia and paraplegia. The reduction in osteolytic lesions, tumor growth in bone, and weight loss was statistically significant in the preventive model compared with the vehicle group. In the therapeutic model, sagopilone treatment significantly lowered the number of activated osteoclasts and significantly reduced the osteolytic lesion area, bone volume loss, and bone resorption compared with vehicle treatment while simultaneously inhibiting tumor burden. An in vitro assay confirmed that sagopilone inhibited osteoclast activation without cytotoxic effects, whereas paclitaxel resulted in lower inhibition and high levels of cytotoxicity. CONCLUSIONS: Sagopilone seems to inhibit the vicious cycle at both the tumor growth and bone resorption stages, suggesting the possibility for substantial benefit in the treatment of patients with breast cancer at risk from bone metastases or with bone lesions already present. Phase II clinical trials with sagopilone in patients with breast cancer are ongoing.