Gadolinium-Based Contrast Agents and Free Gadolinium Inhibit Differentiation and Activity of Bone Cell Lineages.

OBJECTIVES: Administration of gadolinium-based contrast agents (GBCA) in magnetic resonance imaging results in the long-term retention of gadolinium (Gd) in tissues and organs, including the bone, and may affect their function and metabolism. This study aims to investigate the effects of Gd and GBCA on the proliferation/survival, differentiation, and function of bone cell lineages. MATERIALS AND METHODS: Primary murine osteoblasts (OB) and osteoclast progenitor cells (OPC) isolated from C57BL/6J mice were used to test the effects of Gd 3+ (12.5-100 µM) and GBCA (100-2000 µM). Cultures were supplemented with the nonionic linear Gd-DTPA-BMA (gadodiamide), ionic linear Gd-DTPA (gadopentetic acid), and macrocyclic Gd-DOTA (gadoteric acid). Cell viability and differentiation were analyzed on days 4-6 of the culture. To assess the resorptive activity of osteoclasts, the cells were grown in OPC cultures and were seeded onto layers of amorphous calcium phosphate with incorporated Gd. RESULTS: Gd 3+ did not affect OB viability, but differentiation was reduced dose-dependently up to 72.4% ± 6.2%-73.0% ± 13.2% (average ± SD) at 100 µM Gd 3+ on days 4-6 of culture as compared with unexposed controls ( P < 0.001). Exposure to GBCA had minor effects on OB viability with a dose-dependent reduction up to 23.3% ± 10.2% for Gd-DTPA-BMA at 2000 µM on day 5 ( P < 0.001). In contrast, all 3 GBCA caused a dose-dependent reduction of differentiation up to 88.3% ± 5.2% for Gd-DTPA-BMA, 49.8% ± 16.0% for Gd-DTPA, and 23.1% ± 8.7% for Gd-DOTA at 2000 µM on day 5 ( P < 0.001). In cultures of OPC, cell viability was not affected by Gd 3+ , whereas differentiation was decreased by 45.3% ± 9.8%-48.5% ± 15.8% at 100 µM Gd 3+ on days 4-6 ( P < 0.05). Exposure of OPC to GBCA resulted in a dose-dependent increase in cell viability of up to 34.1% ± 11.4% at 2000 µM on day 5 of culture ( P < 0.001). However, differentiation of OPC cultures was reduced on day 5 by 24.2% ± 9.4% for Gd-DTPA-BMA, 47.1% ± 14.0% for Gd-DTPA, and 38.2% ± 10.0% for Gd-DOTA ( P < 0.001). The dissolution of amorphous calcium phosphate by mature osteoclasts was reduced by 36.3% ± 5.3% upon incorporation of 4.3% Gd/Ca wt/wt ( P < 0.001). CONCLUSIONS: Gadolinium and GBCA inhibit differentiation and activity of bone cell lineages in vitro. Thus, Gd retention in bone tissue could potentially impair the physiological regulation of bone turnover on a cellular level, leading to pathological changes in bone metabolism.

Artificial Intelligence and Interstitial Lung Disease: Diagnosis and Prognosis.

ABSTRACT: Interstitial lung disease (ILD) is now diagnosed by an ILD-board consisting of radiologists, pulmonologists, and pathologists. They discuss the combination of computed tomography (CT) images, pulmonary function tests, demographic information, and histology and then agree on one of the 200 ILD diagnoses. Recent approaches employ computer-aided diagnostic tools to improve detection of disease, monitoring, and accurate prognostication. Methods based on artificial intelligence (AI) may be used in computational medicine, especially in image-based specialties such as radiology. This review summarises and highlights the strengths and weaknesses of the latest and most significant published methods that could lead to a holistic system for ILD diagnosis. We explore current AI methods and the data use to predict the prognosis and progression of ILDs. It is then essential to highlight the data that holds the most information related to risk factors for progression, e.g., CT scans and pulmonary function tests. This review aims to identify potential gaps, highlight areas that require further research, and identify the methods that could be combined to yield more promising results in future studies.

Radiation dose in pneumatic reduction of ileo-colic intussusceptions--results from a single-institution study.

BACKGROUND: Air enema under fluoroscopy is a well-accepted procedure for the treatment of childhood intussusception. However, the reported radiation doses of pneumatic reduction with conventional fluoroscopy units have been high in decades past. OBJECTIVE: To compare current radiation doses at our institution to past doses reported by others for fluoroscopic-guided pneumatic reduction of ileo-colic intussusception in children. MATERIALS AND METHODS: Since 2007 radiologists and residents in our department who perform reduction of intussusceptions have received a radiation risk training. We retrospectively analyzed the data of 45 children (5 months-8 years) who underwent a total of 48 pneumatic reductions of ileo-colic intussusception between 2008 and 2012. We analyzed data for screening time and dose area product (DAP) and compared these data to those reported up to and including the year 2000. RESULTS: Our mean screening time measured by the DAP-meter was 53.8 s (range 1-320 s, median 33.0 s). The mean DAP was 11.4 cGy ∙ cm(2) (range 1-145 cGy ∙ cm(2), median 5.45 cGy ∙ cm(2)). There was one bowel perforation, in a 1-year-old boy requiring surgical revision. Only three studies in the literature presented radiation exposure results on children who received pneumatic or hydrostatic reduction of intussusception under fluoroscopy. Screening times and dose area products in those studies, which were published in the 1990 s and in the year 2000, were substantially higher than those in our sample. CONCLUSION: Low-frequency pulsed fluoroscopy and other dose-saving keys as well as the radiation risk training might have helped to improve the quality of the procedure in terms of radiation exposure.

Investigation of correction factors for non-reference conditions in ion chamber photon dosimetry with Monte-Carlo simulations.

Current dosimetry protocols require geometrical reference conditions for the determination of absorbed dose in external radiotherapy. Whenever these geometrical conditions cannot be maintained the application of additional corrections becomes necessary, in principle. The current DIN6800-2 protocol includes a corresponding factor k(NR), but numerical values are lacking and no definite information about the magnitude of this correction is available yet. This study presents Monte-Carlo based calculations within the 6 MV-X photon field of a linear accelerator for a common used ion chamber (PTW31010) employing the EGSnrc code system. The linear accelerator model was matched to measurements, showing good agreement and is used as a realistic source. The individual perturbation correction factors as well as the resulting correction factor k(NR) were calculated as a function of depth for three field sizes, as a function of central axis distance for the largest field and within the build-up region. The behaviour of the ion chamber was further investigated for an idealized hypothetical field boundary. Within the field of the linear accelerator where charged particle equilibrium is achieved the factor k(NR) was generally below approximately 0.5%. In the build-up region a depth dependent correction of up to 2% was calculated when positioning the chamber according to DIN6800-2. Minimizing the depth dependence of the corrections in the build-up region lead to a slightly different positioning of the ion chamber as currently recommended. In regions of the hypothetical field boundary with missing charged particle equilibrium and high dose gradients, the ion chamber response changed by up to approximately 40%, caused by the comparatively large volume (0.125 cm(3)) of the investigated chamber.

Treatment with ozone/oxygen-pneumoperitoneum results in complete remission of rabbit squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCC) represent a group of metastasizing tumors with a high mortality rate in man and animals. Since the biomolecule ozone was found to inhibit growth of various carcinoma cells in vitro we here applied the highly aggressive and lethal VX2 carcinoma HNSCC tumor model of the New Zealand White rabbit to test whether ozone exerts antitumorous effects in vivo. Therapeutic insufflation of medical ozone/oxygen (O(3)/O(2)) gas mixture into the peritoneum (O(3)/O(2)-pneumoperitoneum) at an advanced stage of tumor disease led to a survival rate of 7/14 rabbits. Six of the seven surviving rabbits presented full tumor regression and the absence of local or distant lung metastases. Insufflation of pure oxygen (O(2)) resulted in a survival rate of 3/13 animals accompanied by full tumor remission in 2 of the 3 surviving animals. Of the 14 sham-treated animals only 1 had spontaneous tumor remission and survived. No adverse effects or changes in standard blood parameters were observed after repeated intraperitoneal insufflations of the O(3)/O(2) or O(2) gas. Animals with O(3)/O(2)-induced tumor eradication developed tolerance against reimplantation of the VX2 tumor. This could be reversed by immune suppression with a combination of dexamethasone and cyclosporin A suggesting an antitumorous effect of O(3)/O(2)-mediated activation of the body's own immunosurveillance. Although the exact mechanisms of action are still unclear the present data point to O(3)/O(2)-pneumoperitoneum as a promising new strategy in anticancer therapy.