Renormalization of radiobiological response functions by energy loss fluctuations and complexities in chromosome aberration induction: deactivation theory for proton therapy from cells to tumor control

We employ a multi-scale mechanistic approach to investigate radiation induced cell toxicities and deactivation mechanisms as a function of linear energy transfer in hadron therapy. Our theoretical model consists of a system of Markov chains in microscopic and macroscopic spatio-temporal landscapes, i.e., stochastic birth-death processes of cells in millimeter-scale colonies that incorporates a coarse-grained driving force to account for microscopic radiation induced damage. The coupling, hence the driving force in this process, stems from a nano-meter scale radiation induced DNA damage that incorporates the enzymatic end-joining repair and mis-repair mechanisms. We use this model for global fitting of the high-throughput and high accuracy clonogenic cell-survival data acquired under exposure of the therapeutic scanned proton beams, the experimental design that considers $\gamma$-H2AX as the biological endpoint and exhibits maximum observed achievable dose and LET, beyond which the majority of the cells undergo collective biological deactivation processes. An estimate to optimal dose and LET calculated from tumor control probability by extension to $~ 10^6$ cells per $mm$-size voxels is presented. We attribute the increase in degree of complexity in chromosome aberration to variabilities in the observed biological responses as the beam linear energy transfer (LET) increases, and verify consistency of the predicted cell death probability with the in-vitro cell survival assay of approximately 100 non-small cell lung cancer (NSCLC) cells

Can megavoltage computed tomography reduce proton range uncertainties in treatment plans for patients with large metal implants?

Treatment planning calculations for proton therapy require an accurate knowledge of radiological path length, or range, to the distal edge of the target volume. In most cases, the range may be calculated with sufficient accuracy using kilovoltage (kV) computed tomography (CT) images. However, metal implants such as hip prostheses can cause severe streak artifacts that lead to large uncertainties in proton range. The purposes of this study were to quantify streak-related range errors and to determine if they could be avoided by using artifact-free megavoltage (MV) CT images in treatment planning. Proton treatment plans were prepared for a rigid, heterogeneous phantom and for a prostate cancer patient with a metal hip prosthesis using corrected and uncorrected kVCT images alone, uncorrected MVCT images and a combination of registered MVCT and kVCT images (the hybrid approach). Streak-induced range errors of 5-12 mm were present in the uncorrected kVCT-based patient plan. Correcting the streaks by manually assigning estimated true Hounsfield units improved the range accuracy. In a rigid heterogeneous phantom, the implant-related range uncertainty was estimated at approach, the kVCT images provided good delineation of soft tissues due to high-contrast resolution, and the streak-free MVCT images provided smaller range uncertainties because they did not require artifact correction. © 2008 Institute of Physics and Engineering in Medicine

PLY WISE FAILURE ANALYSIS OF MONO LEAF SPRING USING HYBRID C-GFRP COMPOSITES

Composite materials are a better alternative for Leaf spring material in automobiles since they have higher stiffness, high impact energy absorption, lesser stresses and also higher strength to weight ratio. The objective is to study the ply wise failure criteria in the composite leaf springs. Leaf springs are modeled and analyzed using ACP PrePost and studied for failure criteria based on four failure theories which are: maximum stress failure theory, maximum strain failure theory, Tsai-Hill failure theory and Tsai-Wu failure theory. Failure load based on these theories is calculated by conducting a parametric study. To improve the maximum failure load, hybrid composites are designed and analyzed by replacing the top, bottom and center layers of the composite laminate. The four different cross-sections which are analyzed are Eglass/epoxy, HC1, HC2 and HC3. The study shows that replacing the top, bottom and center layers does improve the maximum failure load. Although this introduces higher stresses in the component, the stresses in the Eglass/epoxy material at the same positions from the center of the laminate are reduced. HC3 shows 30.7% increment in failure load by considering only vertical loads and 20.8% increment in failure load by considering vertical, side loads and twist moment simultaneously. There is an agreeable error of 1.44 – 1.65% in the results obtained for deformation and 0.88 – 1.33% for failure load between simulation and theoretical calculations. Mechanical properties of the Eglass/epoxy material are evaluated by conducting tensile test and three-point bending test. Mono leaf spring similar to the dimensions of Maruthi 800 vehicle is made using hand layup method. The load vs deformation results of leaf spring show a good agreement between the experimental and the simulation values

Differential tissue sparing of FLASH ultra high dose rates: an {\it in-silico} study

Purpose: To propose a theory for the differential tissue sparing of FLASH ultra high dose rates (UHDR) through inter-track reaction-diffusion mechanism. Methods: We calculate the time-evolution of particle track-structures using a system of coupled reaction-diffusion equations on a random network designed for molecular transport in porous and disordered media. The network is representative of the intra- and inter-cellular diffusion channels in tissues. Spatial cellular heterogeneities over the scale of track spacing have been constructed by incorporating random fluctuations in the connectivity among network sites. Results: We demonstrate the occurrence of phase separation among the tracks as the complexity in intra- and inter-cellular structural increases. At the weak limit of disorder, such as in water and normal tissue, neighboring tracks melt into each other and form a percolated network of nonreactive species. In contrast, at the strong limit of disorder, tracks evolve individually like isolated islands with negligible inter-track overlap. Thus, the spatio-temporal correlation among the chemical domains decreases as the inter-cellular complexity of the tissue increases (e.g. from normal tissue to fractal-type malignant tissue). Conclusions: The differential sparing of FLASH UHDR in normal and tumor tissue may be explained by differences in inter- and intra-cellular structural complexities between the tissue types. The structural complexities of cancerous cells prevent clustering and chemical interaction of tracks, whereas this interaction prevails and thus leads to sparing in normal tissue

A step towards true delivered dose with dose accumulation in radiotherapy

https://openworks.mdanderson.org/sumexp21/1188/thumbnail.jp