Concise matrix analysis of point-based prostate targeting for intensity modulated radiation therapy.

Intensity Modulated Radiation Therapy (IMRT) has recently emerged as an effective clinical treatment tool to treat various types of cancers by limiting the external beam dose to the surrounding normal tissue. However, the process of limiting external radiation dose to the tissue surrounding the tumor volume is not a trivial task. Several parameters including tumor volume and inhomogeneity, position and shape of the tumor volume, and the geometrical distribution of the radiation beams directly affect the determination of the external radiation dose. In addition, a major variable in effective delivery of the radiation dose is "set-up error" caused by the changes in patient position. Any changes in the position of the patient affect the geometrical location of the tumor volume and, therefore, need to be accommodated in the delivery of radiation beams during the treatment. This work presents a complete matrix representation required to calculate the three-dimensional rigid body homogeneous transformation matrices corresponding to external beam radiotherapy setup error and subsequent corrections in treatment beam parameters. A new concise orthogonal rotation solution is presented for use with clinical noisy data. Monte Carlo simulations prove the new matrix results are consistently better than the standard inverse solution. The required corrections in beam table, gantry, and collimator angles as function of the planned beam gantry angle are derived. For transformations that include a rotation on the sagittal plane, the required offsets to beam parameters are complex functions of the planned gantry angle but are clearly documented graphically for clinical use. A case study is presented with an error analysis that supports the use of the presented method in a clinical environment. Clinical implementation and evaluation of the presented method with patient data is also included in the paper.

A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

A clinical procedure for case-specific analytical validation of mono-modality image fusion in image guided radiotherapy.

Image guided radiotherapy can be performed by fusing the daily treatment and reference planning computed tomography scans. Decreased errors in patient setup can lead to smaller target margins that significantly improve treatment efficacy and outcome. The purpose of this work is to present a clinical procedure to analytically compute the accuracy of the registration. Accepted techniques such as normalized mutual information intensity based three-dimensional image registration can be validated using a large automated point sample. Without a user independent metric it is not possible to determine effect of the fusion error on the calculated correction in patient setup.