X-Ray Phase Contrast 3D Virtual Histology: Evaluation of Lung Alterations After Microbeam Irradiation.

PURPOSE: This study provides the first experimental application of multiscale 3-dimensional (3D) x-ray phase contrast imaging computed tomography (XPCI-CT) virtual histology for the inspection and quantitative assessment of the late-stage effects of radio-induced lesions on lungs in a small animal model. METHODS AND MATERIALS: Healthy male Fischer rats were irradiated with x-ray standard broad beams and microbeam radiation therapy, a high-dose rate (14 kGy/s), FLASH spatially fractionated x-ray therapy to avoid beamlet smearing owing to cardiosynchronous movements of the organs during the irradiation. After organ dissection, ex vivo XPCI-CT was applied to all the samples and the results were quantitatively analyzed and correlated to histologic data. RESULTS: XPCI-CT enables the 3D visualization of lung tissues with unprecedented contrast and sensitivity, allowing alveoli, vessel, and bronchi hierarchical visualization. XPCI-CT discriminates in 3D radio-induced lesions such as fibrotic scars and Ca/Fe deposits and allows full-organ accurate quantification of the fibrotic tissue within the irradiated organs. The radiation-induced fibrotic tissue content is less than 10% of the analyzed volume for all microbeam radiation therapy-treated organs and reaches 34% in the case of irradiations with 50 Gy using a broad beam. CONCLUSIONS: XPCI-CT is an effective imaging technique able to provide detailed 3D information for the assessment of lung pathology and treatment efficacy in a small animal model.

New PK/PD model directly links diabetes drug dose to blood glucose level for personalized care.

The management of diabetes mellitus focuses on close monitoring of a patient's blood glucose level while the clinician experiments with a dosing strategy using clinical guidelines and his/her own experience. We propose a pharmacokinetic and pharmacodynamics model that characterizes the dose-response of patients receiving anti-diabetic drug therapy. We derive and establish a direct relationship between drug dosage and blood glucose level. This new drug-dose drug-effect model, combined with a linear disease progression model, is used to fit the patient's daily self-monitored blood glucose (SMBG) data to obtain the personalized treatment effect for each patient. The model predicts the long-term drug effect using the prescribed dose, thus allowing for dose optimization. The model is evaluated on patients with gestational diabetes mellitus. SMBG data collected during the first month of treatment is used to train the model. The model is able to characterize the personalized dose-response and disease progression. Moreover, when compared to a descriptive autoregression model, our model gives a better long-term prediction of the drug effect on the trend of the blood glucose level. This mechanism-based treatment effect model utilizes daily recorded blood glucose data to estimate and predict a patient's personalized dose-response and disease progression. Such evidence can be used by clinicians to individualize and optimize dose regimens to achieve better treatment outcomes.

Non-conventional Ultra-High Dose Rate (FLASH) Microbeam Radiotherapy Provides Superior Normal Tissue Sparing in Rat Lung Compared to Non-conventional Ultra-High Dose Rate (FLASH) Radiotherapy.

Conventional radiotherapy is a widely used non-invasive form of treatment for many types of cancer. However, due to a low threshold in the lung for radiation-induced normal tissue damage, it is of less utility in treating lung cancer. For this reason, surgery is the preferred treatment for lung cancer, which has the detriment of being highly invasive. Non-conventional ultra-high dose rate (FLASH) radiotherapy is currently of great interest in the radiotherapy community due to demonstrations of reduced normal tissue toxicity in lung and other anatomy. This study investigates the effects of FLASH microbeam radiotherapy, which in addition to ultra-high dose rate incorporates a spatial segmentation of the radiation field, on the normal lung tissue of rats. With a focus on fibrotic damage, this work demonstrates that FLASH microbeam radiotherapy provides an order of magnitude increase in normal tissue radio-resistance compared to FLASH radiotherapy. This result suggests FLASH microbeam radiotherapy holds promise for much improved non-invasive control of lung cancer.

Microbeam radiosurgery: An industrial perspective.

In spite of its long demonstrated potential, microbeam radiosurgery (MBRS) has yet to be developed into a clinical tool. This article examines the problems associated with MBRS, and potential solutions. It is shown that a path to a clinically useful device is emerging.

Comparison of three systems for the polishing of an ultra-low fusing dental porcelain.

STATEMENT OF THE PROBLEM: With the introduction of newer dental porcelains, there exists the need to evaluate different porcelain polishing systems available on the market. PURPOSE: The purpose of this study was to compare the surface roughness produced by 3 different porcelain polishing systems on an ultra-low fusing porcelain. MATERIAL AND METHODS: Sixty-three ultra-low fusing porcelain (Finesse) discs (10 x 2 mm) were fabricated and randomly divided into 3 groups (n=21). Both sides of each disc were abraded with a medium-grit diamond bur. One side was autoglazed and was considered a control. The other side was polished until the surface appeared shiny to the naked eye using 1 of 3 porcelain polishing kits (Axis Dental, Jelenko, and Brasseler systems). The surface of each disc was evaluated quantitatively with surface profilometry and qualitatively using scanning electron microscopy (SEM). A mean roughness profile (Ra) value was determined for each side of each specimen to describe the overall roughness of the surface. The Ra mean difference for each specimen was determined by subtracting the mean experimental readings (polished surface) from the mean control readings (glazed surface) and was used for the statistical analysis. The data were analyzed using analysis of variance followed by a Tukey multiple comparison test (alpha=.05). Representative specimens from each group were evaluated by scanning electron microscopy. RESULTS: The Axis porcelain polishing system produced a smoother surface than the Brasseler or Jelenko systems (0.586 +/- 0.256, 0.306 +/- 0.238, and 0.277 +/- 0.230, respectively). No significant difference was found between the Jelenko and Brasseler porcelain polishing kits (F=10.6, P <.001). The images obtained through SEM were evaluated and found to be consistent with the profilometer readings. CONCLUSION: Within the limitations of this study, all 3 porcelain polishing systems produced a surface smoother than the autoglazed surface of Finesse. The Axis system provided a significantly smoother surface compared to the Brasseler and Jelenko polishing systems.