Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions

Percutaneous thermal ablation has proved to be an effective modality for treating both benign and malignant tumors in various tissues. Among these modalities, radiofrequency ablation (RFA) is the most promising and widely adopted approach that has been extensively studied in the past decades. Microwave ablation (MWA) is a newly emerging modality that is gaining rapid momentum due to its capability of inducing rapid heating and attaining larger ablation volumes, and its lesser susceptibility to the heat sink effects as compared to RFA. Although the goal of both these therapies is to attain cell death in the target tissue by virtue of heating above 50 oC, their underlying mechanism of action and principles greatly differs. Computational modelling is a powerful tool for studying the effect of electromagnetic interactions within the biological tissues and predicting the treatment outcomes during thermal ablative therapies. Such a priori estimation can assist the clinical practitioners during treatment planning with the goal of attaining successful tumor destruction and preservation of the surrounding healthy tissue and critical structures. This review provides current state-of- the-art developments and associated challenges in the computational modelling of thermal ablative techniques, viz., RFA and MWA, as well as touch upon several promising avenues in the modelling of laser ablation, nanoparticles assisted magnetic hyperthermia and non- invasive RFA. The application of RFA in pain relief has been extensively reviewed from modelling point of view. Additionally, future directions have also been provided to improve these models for their successful translation and integration into the hospital work flow

Space Radiation Cancer Risk Projections and Uncertainties - 2010

Uncertainties in estimating health risks from galactic cosmic rays greatly limit space mission lengths and potential risk mitigation evaluations. NASA limits astronaut exposures to a 3% risk of exposure-induced death and protects against uncertainties using an assessment of 95% confidence intervals in the projection model. Revisions to this model for lifetime cancer risks from space radiation and new estimates of model uncertainties are described here. We review models of space environments and transport code predictions of organ exposures, and characterize uncertainties in these descriptions. We summarize recent analysis of low linear energy transfer radio-epidemiology data, including revision to Japanese A-bomb survivor dosimetry, longer follow-up of exposed cohorts, and reassessments of dose and dose-rate reduction effectiveness factors. We compare these projections and uncertainties with earlier estimates. Current understanding of radiation quality effects and recent data on factors of relative biological effectiveness and particle track structure are reviewed. Recent radiobiology experiment results provide new information on solid cancer and leukemia risks from heavy ions. We also consider deviations from the paradigm of linearity at low doses of heavy ions motivated by non-targeted effects models. New findings and knowledge are used to revise the NASA risk projection model for space radiation cancer risks

Evidence Report: Risk of Radiation Carcinogenesis

As noted by Durante and Cucinotta (2008), cancer risk caused by exposure to space radiation is now generally considered a main hindrance to interplanetary travel for the following reasons: large uncertainties are associated with the projected cancer risk estimates; no simple and effective countermeasures are available, and significant uncertainties prevent scientists from determining the effectiveness of countermeasures. Optimizing operational parameters such as the length of space missions, crew selection for age and sex, or applying mitigation measures such as radiation shielding or use of biological countermeasures can be used to reduce risk, but these procedures have inherent limitations and are clouded by uncertainties. Space radiation is comprised of high energy protons, neutrons and high charge (Z) and energy (E) nuclei (HZE). The ionization patterns and resulting biological insults of these particles in molecules, cells, and tissues are distinct from typical terrestrial radiation, which is largely X-rays and gamma-rays, and generally characterized as low linear energy transfer (LET) radiation. Galactic cosmic rays (GCR) are comprised mostly of highly energetic protons with a small component of high charge and energy (HZE) nuclei. Prominent HZE nuclei include He, C, O, Ne, Mg, Si, and Fe. GCR ions have median energies near 1 GeV/n, and energies as high as 10 GeV/n make important contributions to the total exposure. Ionizing radiation is a well known carcinogen on Earth (BEIR 2006). The risks of cancer from X-rays and gamma-rays have been established at doses above 50 mSv (5 rem), although there are important uncertainties and on-going scientific debate about cancer risk at lower doses and at low dose rates (<50 mSv/h). The relationship between the early biological effects of HZE nuclei and the probability of cancer in humans is poorly understood, and it is this missing knowledge that leads to significant uncertainties in projecting cancer risks during space exploration (Cucinotta and Durante 2006; Durante and Cucinotta 2008)

Developing novel fluorescent probe for peroxynitrite: implication for understanding the roles of peroxynitrite and drug discovery in cerebral ischemia reperfusion injury

Session 7 - Oral PresentationsSTUDY GOAL: Peroxynitrite (ONOO‐) is a cytotoxic factor. As its short lifetime, ONOO‐ is hard to be detected in biological systems. This study aims to develop novel probe for detecting ONOO‐ and understand the roles of ONOO‐ in ischemic brains and drug discovery ABSTRACT: MitoPN‐1 was found to be a ONOO‐ specific probe with no toxicity. With MitoPN‐1, we studied the roles of ONOO‐ in hypoxic neuronal cells in vitro and MCAO …postprin

Space radiation health research, 1991-1992

The present volume is a collection of 227 abstracts of radiation research sponsored by the NASA Space Radiation Health Program for the period 1991-1992. Each abstract has been categorized within one of three discipline areas: Physics, Biology and Risk Assessment. Topic areas within each discipline have been assigned as follows: Physics - Atomic Physics, Theory, Cosmic Ray and Astrophysics, Experimental, Environments and Environmental Models, Solar Activity and Prediction, Experiments, Radiation Transport and Shielding, Theory and Model Development, Experimental Studies, and Instrumentation. Biology - Biology, Molecular Biology, Cellular Radiation Biology, Transformation, Mutation, Lethality, Survival, DNA Damage and Repair, Tissue, Organs, and Organisms, In Vivo/In Vitro Systems, Carcinogenesis and Life Shortening, Cataractogenesis, Genetics/Developmental, Radioprotectants, Plants, and Other Effects. Risk Assessment - Risk Assessment, Radiation Health and Epidemiology, Space Flight Radiation Health Physics, Inter- and Intraspecies Extrapolation and Radiation Limits and Standards. Section I contains refereed journals; Section II contains reports/meetings. Keywords and author indices are provided. A collection of abstracts spanning the period 1986-1990 was previously issued as NASA Technical Memorandum 4270

Dual-energy computed tomography for predicting range in particle therapy

Radiotherapy with protons or light ions is a highly precise form of cancer treatment. In treatment planning for particle therapy, ion stopping power ratio (SPR) maps of patient tissues are used to predict particle ranges and calculate dose distributions. To more accurately calculate dose distributions and minimize irradiating healthy tissue, it is crucial to improve SPR prediction. To this end, this thesis investigated dual-layer spectral computed tomography, a dual-energy CT (DECT) technique, as an alternative to conventional single-energy CT (SECT). The SECT-based method relies on converting CT numbers to SPR, yet CT numbers acquired from photon attenuation cannot be used to accurately predict energy loss by ions, which makes the approach indirect and heuristic. The DECT-based method, however, uses measurements of relative electron density and effective atomic number to directly and patient-specifically predict SPR. SPR prediction using DECT was evaluated in tissue-equivalent materials, anthropomorphic phantoms, and non-tissue materials; clinically analyzed in a retrospective patient study; and experimentally investigated for patients with dental materials. DECT-based SPR prediction improved dose calculation accuracy in particle therapy compared to SECT with a remaining range uncertainty of about 1% in controlled experimental scenarios. DECT may thus substantially improve range prediction for highly accurate particle therapy

Nanoparticle Enhanced Radiotherapy

Nanoparticles have been shown to create a localised increase in dose deposition when combined with ionising radiation. Although this has been shown in the literature, there are several factors that can alter the level of enhancement, which need to be investigated before translating the use of nanoparticles for clinical treatments. This thesis aims to investigate three different aspects of this effect: (i) effect of nanoparticles when combined with proton therapy, (ii) study the combined effect of nanoparticle material, size and beam energy with photon irradiation, (iii) consider the biological impact with different cell lines, nanoparticle parameters and radiation types. To consider the effect of nanoparticles with protons, Monte Carlo simulations were developed to model the effects of nanoparticle concentrations. The use of nanoparticles at clinically relevant concentrations was shown to cause an effect on the Bragg peak, where changes were quantified in the model and validated experimentally. Both simulation and experiment demonstrated a shift in the distal edge of the Bragg peak, with a simulated shift of 4.5 mm compared to a measured shift of 2.2 mm with a beam of 226 MeV protons. To study the combined effect, another model was developed, studying the effect on dose deposition around a single nanoparticle with photon irradiation. Here the geometry could be altered such that the nanoparticle size and material were studied, as well as the effect of different incident beam energies. These simulations considered the effects on multiple scales to determine the extent of the enhancement, where it is then possible to inform where nanoparticles need to be localised to within a cell to observe the most beneficial effect. The highest level of enhancement was found with 2 nm gold nanoparticles and 90 keV photons. Finally to investigate the biological impact, an in vitro model was used with different cell lines, nanoparticles and radiation types, to gain an understanding of the biological effects. This was able to show differences in cell survival when comparing different cell lines, with different levels of radiosensitivity. As well as this, differences in DNA damage were shown when comparing X-ray radiotherapy and proton therapy. In terms of enhancement, gold nanoparticles were shown to be more effective with MCF-7 cells, whereas gadolinium based nanoparticles caused more cell kill for U87 cells