The Feasibly of Functionally Guided Intensity Modulated Radiation Therapy Treatment Planning Using Perfluoropropane-Enhanced MRI for Lung Cancer

Radiotherapy is commonly used to treat lung cancer. However, radiation induced damage to lung tissue is a major limiting factor to its use. To minimize normal tissue lung toxicity from conformal radiotherapy treatment planning, we investigated the use of Perfluoropropane(PFP)-enhanced MR imaging to assess and guide the sparing of functioning lung. Fluorine Enhanced MRI using Perfluoropropane(PFP) is a dynamic multi-breath steady state technique enabling quantitative and qualitative assessments of lung function(1).

Imaging data was obtained from studies previously acquired in the Duke Image Analysis Laboratory. All studies were approved by the Duke IRB. The data was de-identified for this project, which was also approved by the Duke IRB. Subjects performed several breath-holds at total lung capacity(TLC) interspersed with multiple tidal breaths(TB) of Perfluoropropane(PFP)/oxygen mixture. Additive wash-in intensity images were created through the summation of the wash-in phase breath-holds. Additionally, model based fitting was utilized to create parametric images of lung function(1).

Varian Eclipse treatment planning software was used for putative treatment planning. For each subject two plans were made, a standard plan, with no regional functional lung information considered other than current standard models. Another was created using functional information to spare functional lung while maintaining dose to the target lesion. Plans were optimized to a prescription dose of 60 Gy to the target over the course of 30 fractions.

A decrease in dose to functioning lung was observed when utilizing this functional information compared to the standard plan for all five subjects. PFP-enhanced MR imaging is a feasible method to assess ventilatory lung function and we have shown how this can be incorporated into treatment planning to potentially decrease the dose to normal tissue.

Prospective Estimation of Radiation Dose and Image Quality for Optimized CT Performance

X-ray computed tomography (CT) is a non-invasive medical imaging technique that generates cross-sectional images by acquiring attenuation-based projection measurements at multiple angles. Since its first introduction in the 1970s, substantial technical improvements have led to the expanding use of CT in clinical examinations. CT has become an indispensable imaging modality for the diagnosis of a wide array of diseases in both pediatric and adult populations [1, 2]. Currently, approximately 272 million CT examinations are performed annually worldwide, with nearly 85 million of these in the United States alone [3]. Although this trend has decelerated in recent years, CT usage is still expected to increase mainly due to advanced technologies such as multi-energy [4], photon counting [5], and cone-beam CT [6].

Despite the significant clinical benefits, concerns have been raised regarding the population-based radiation dose associated with CT examinations [7]. From 1980 to 2006, the effective dose from medical diagnostic procedures rose six-fold, with CT contributing to almost half of the total dose from medical exposure [8]. For each patient, the risk associated with a single CT examination is likely to be minimal. However, the relatively large population-based radiation level has led to enormous efforts among the community to manage and optimize the CT dose.

As promoted by the international campaigns Image Gently and Image Wisely, exposure to CT radiation should be appropriate and safe [9, 10]. It is thus a responsibility to optimize the amount of radiation dose for CT examinations. The key for dose optimization is to determine the minimum amount of radiation dose that achieves the targeted image quality [11]. Based on such principle, dose optimization would significantly benefit from effective metrics to characterize radiation dose and image quality for a CT exam. Moreover, if accurate predictions of the radiation dose and image quality were possible before the initiation of the exam, it would be feasible to personalize it by adjusting the scanning parameters to achieve a desired level of image quality. The purpose of this thesis is to design and validate models to quantify patient-specific radiation dose prospectively and task-based image quality. The dual aim of the study is to implement the theoretical models into clinical practice by developing an organ-based dose monitoring system and an image-based noise addition software for protocol optimization.

More specifically, Chapter 3 aims to develop an organ dose-prediction method for CT examinations of the body under constant tube current condition. The study effectively modeled the anatomical diversity and complexity using a large number of patient models with representative age, size, and gender distribution. The dependence of organ dose coefficients on patient size and scanner models was further evaluated. Distinct from prior work, these studies use the largest number of patient models to date with representative age, weight percentile, and body mass index (BMI) range.

With effective quantification of organ dose under constant tube current condition, Chapter 4 aims to extend the organ dose prediction system to tube current modulated (TCM) CT examinations. The prediction, applied to chest and abdominopelvic exams, was achieved by combining a convolution-based estimation technique that quantifies the radiation field, a TCM scheme that emulates modulation profiles from major CT vendors, and a library of computational phantoms with representative sizes, ages, and genders. The prospective quantification model is validated by comparing the predicted organ dose with the dose estimated based on Monte Carlo simulations with TCM function explicitly modeled.

Chapter 5 aims to implement the organ dose-estimation framework in clinical practice to develop an organ dose-monitoring program based on a commercial software (Dose Watch, GE Healthcare, Waukesha, WI). In the first phase of the study we focused on body CT examinations, and so the patient’s major body landmark information was extracted from the patient scout image in order to match clinical patients against a computational phantom in the library. The organ dose coefficients were estimated based on CT protocol and patient size as reported in Chapter 3. The exam CTDIvol, DLP, and TCM profiles were extracted and used to quantify the radiation field using the convolution technique proposed in Chapter 4.

With effective methods to predict and monitor organ dose, Chapters 6 aims to develop and validate improved measurement techniques for image quality assessment. Chapter 6 outlines the method that was developed to assess and predict quantum noise in clinical body CT images. Compared with previous phantom-based studies, this study accurately assessed the quantum noise in clinical images and further validated the correspondence between phantom-based measurements and the expected clinical image quality as a function of patient size and scanner attributes.

Chapter 7 aims to develop a practical strategy to generate hybrid CT images and assess the impact of dose reduction on diagnostic confidence for the diagnosis of acute pancreatitis. The general strategy is (1) to simulate synthetic CT images at multiple reduced-dose levels from clinical datasets using an image-based noise addition technique; (2) to develop quantitative and observer-based methods to validate the realism of simulated low-dose images; (3) to perform multi-reader observer studies on the low-dose image series to assess the impact of dose reduction on the diagnostic confidence for multiple diagnostic tasks; and (4) to determine the dose operating point for clinical CT examinations based on the minimum diagnostic performance to achieve protocol optimization.

Chapter 8 concludes the thesis with a summary of accomplished work and a discussion about future research.

Global surface net-radiation at 5 km from MODIS Terra

Reliable and fine resolution estimates of surface net-radiation are required for estimating latent and sensible heat fluxes between the land surface and the atmosphere. However, currently, fine resolution estimates of net-radiation are not available and consequently it is challenging to develop multi-year estimates of evapotranspiration at scales that can capture land surface heterogeneity and are relevant for policy and decision-making. We developed and evaluated a global net-radiation product at 5 km and 8-day resolution by combining mutually consistent atmosphere and land data from the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Terra. Comparison with net-radiation measurements from 154 globally distributed sites (414 site-years) from the FLUXNET and Surface Radiation budget network (SURFRAD) showed that the net-radiation product agreed well with measurements across seasons and climate types in the extratropics (Wilmott’s index ranged from 0.74 for boreal to 0.63 for Mediterranean sites). Mean absolute deviation between the MODIS and measured net-radiation ranged from 38.0 ± 1.8 W∙m−2 in boreal to 72.0 ± 4.1 W∙m−2 in the tropical climates. The mean bias was small and constituted only 11%, 0.7%, 8.4%, 4.2%, 13.3%, and 5.4% of the mean absolute error in daytime net-radiation in boreal, Mediterranean, temperate-continental, temperate, semi-arid, and tropical climate, respectively. To assess the accuracy of the broader spatiotemporal patterns, we upscaled error-quantified MODIS net-radiation and compared it with the net-radiation estimates from the coarse spatial (1° × 1°) but high temporal resolution gridded net-radiation product from the Clouds and Earth’s Radiant Energy System (CERES). Our estimates agreed closely with the net-radiation estimates from the CERES. Difference between the two was less than 10 W•m−2 in 94% of the total land area. MODIS net-radiation product will be a valuable resource for the science community studying turbulent fluxes and energy budget at the Earth’s surface.

Combined effects of solar UV radiation and CO2-induced seawater acidification on photosynthetic carbon fixation of phytoplankton assemblages in the South China Sea, 2010

We carried out short term pCO2/pH perturbation experiments in the coastal waters of the South China Sea to evaluate the combined effects of seawater acidification (low pH/high pCO2) and solar UV radiation (UVR, 280-400 nm) on photosynthetic carbon fixation of phytoplankton assemblages. Under photosynthetically active radiation (PAR) alone treatments, reduced pCO2 (190 ppmv) with increased pH resulted in a significant decrease in the photosynthetic carbon fixation rate (about 23%), while enriched pCO2 (700 ppmv) with lowered pH had no significant effect on the photosynthetic performance compared to the ambient level. The apparent photosynthetic efficiency decreased under the reduced pCO2 level, probably due to C-limitation as well as energy being diverged for up-regulation of carbon concentrating mechanisms (CCMs). In the presence of UVR, both UV-A and UV-B caused photosynthetic inhibition, though UV-A appeared to enhance the photosynthetic efficiency under lower PAR levels. UV-B caused less inhibition of photosynthesis under the reduced pCO2 level, probably because of its contribution to the inorganic carbon (Ci)-acquisition processes. Under the seawater acidification conditions (enriched pCO2), both UV-A and UV-B reduced the photosynthetic carbon fixation to higher extents compared to the ambient pCO2 conditions. We conclude that solar UV and seawater acidification could synergistically inhibit photosynthesis.

Growth and photosynthesis of a diatom Cylindrotheca closterium grown under elevated CO2 in the presence of solar UV radiation

The combination of elevated CO2 and the increased acidity in surface oceans is likely to have an impact on photosynthesis via its effects on inorganic carbon speciation and on the overall energetics of phytoplankton. Exposure to UV radiation (UVR) may also have a role in the response to elevated CO2 and acidification, due to the fact that UVR may variously impact on photosynthesis and because of the energy demand of UVR defense. The cell may gain energy by down-regulating the CO2 concentrating mechanism, which may lead to a greater ability to cope with UVR and/or higher growth rates. In order to clarify the interplay of cell responses to increasing CO2 and UVR, we investigated the photosynthetic response of the marine and estuarine diatom Cylindrotheca closterium f. minutissima cultured at either 390 (ambient) or 800 (elevated) ppmv CO2, while exposed to solar radiation with or without UVR (UVR, 280-400 nm). After a 6 day acclimation period, the growth rate of cells was little affected by elevated CO2 and no obvious correlation with the radiation dose (for both PAR and PAR + UV treatments) could be detected. However, the relative electron transport rate was reduced and was more sensitive to UVR in cells main - tained at elevated CO2 as compared to cells cultured at ambient CO2. The CO2 concentrating mechanism was down regulated at 800 ppmv CO2, but was apparently not completely switched off. These data are discussed with respect to their significance in the context of global climate change.

Radiation flux from the upper and lower hemispheres in the visible spectral range

This paper describes measurements from shortwave radiation radiosonde ascents done at the Atlantische Expedition 1969. Using the results from a total of 67 ascents mean components of the shortwave radiation budget of the atmospheric layer between the ocean surface and the top of the ascent are discussed. The influence of clouds on the radiation balance is shown by dividing the ascents in classes of cloudiness and cloud altitude. Thereby the albedo of the ocean surface is increasing with increasing amount of cloudiness. Similar the albedo of the troposphere increases involving an increased heating rate of the atmospheric layer.

Analysis of radiation induced DNA damage by LC-MS/MS in isolated and cellular DNA

Abstract: It is well established that ionizing radiation induces a variety of damage in DNA by direct effects that are mediated by one-electron oxidation and indirect effects that are mediated by the reaction of water radiolysis products, e.g., hydroxyl radicals (•OH). In cellular DNA, direct and indirect effects appear to have about an equal effect toward DNA damage. We have shown that ϒ-(gamma) ray irradiation of aqueous solutions of DNA, during which •OH is the major damaging ROS can lead to the formation several lesions. On the other hand, the methylation and oxidative demethylation of cytosine in CpG dinucleotides plays a critical role in the gene regulation. The C5 position of cytosine in CG dinucleotides is frequently methylated by DNA methyl transferees (DNMTs) and constitutes 4-5% of the total cytosine. Here, my PhD research work focuses on the analysis of oxidative base modifications of model compounds of methylated and non methylated oligonucleotides, isolated DNA (calf-thymus DNA) and F98 cultured cell by gamma radiation. In addition, we identified a series of modifications of the 2-deoxyribose moiety of DNA arising from the exposure of isolated and cellular DNA to ionizing radiation. We also studied one electron oxidation of cellular DNA in cultured human HeLa cells initiated by intense nanosecond 266 nm laser pulse irradiation, which produces cross-links between guanine and thymine bases (G*-T*). To achieve these goals, we developed several methods based on mass spectrometry to analyze base modifications in isolated DNA and cellular DNA.

Gamma radiation preserves chemical and bioactive properties of Boletus edulis wild mushrooms

Boletus edulis Bull: Fr. is an edible mushroom quite appreciated for its organoleptic and nutritional properties. However, the seasonality and perishability cause some difficulties in its distribution and marketing in fresh form; losses associated with this type of food during marketing can reach 40% [1]. Irradiation is recognized as a safe and effective method for food preservation, being used worldwide to increase shelf life of fresh and dehydrated products (e.g. fruits, vegetables and spices) [2]. In particular, gamma irradiation has already been applied to cultivated mushrooms (especially Agaricus, Lentinula and Pleurotus Genus) and proved to be an interesting conservation technology [3]. However, the studies with added-value wild species are scarce. In this work, the effects of gamma irradiation on chemical and antioxidant properties of wild B. edulis, were evaluated. Fruiting bodies were obtained in Trás-os-Montes, in the Northeast of Portugal, in November 2012. The irradiation was performed in experimental equipment with 60Co sources at 1 and 2 kGy. All the results were compared with nonirradiated samples (control). Macronutrients and energy value were determined following official procedures of food analysis; fatty acids were analyzed by gas-chromatography coupled to flame ionization detection (GC-FID), while sugars and tocopherols were determined by high performance liquid chromatography (HPLC) coupled to refraction index (RI) and fluorescence detectors, respectively. Antioxidant activity was evaluated in the methanolic extracts by in vitro assays measuring DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of β- carotene bleaching and inhibition of lipid peroxidation using thiobarbituric acid reactive substances (TBARS) assay. Total phenolics were also determined by the Folin-Ciocalteu assay. The nutritional profiles were not affected in high extension. Fatty acids and sugars were slightly affected, decreasing with the increasing doses. The performed assays for antioxidant activity, indicate that irradiated samples tended to have lower scavenging activity and reducing power, but higher lipid peroxidation inhibition. Despite the detected differences in individual compounds, the results of nutritional parameters, the most relevant in terms of mushroom acceptability by consumers, were less affected, indicating an interesting potential of gamma-irradiation to be used as an effective conservation technology for the studied mushrooms.

Quality control of gamma irradiated dwarf mallow (Malva neglecta Wallr.) based on color, organic acids, total phenolics and antioxidant parameters

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to a photodiode array (PDA) detector. Total phenolics and flavonoids were measured by the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The antioxidant activity was evaluated based on the DPPH(•) scavenging activity, reducing power, β-carotene bleaching inhibition and thiobarbituric acid reactive substances (TBARS) formation inhibition. Analyses were performed in the non-irradiated and irradiated plant material, as well as in decoctions obtained from the same samples. The total amounts of organic acids and phenolics recorded in decocted extracts were always higher than those found in the plant material or hydromethanolic extracts, respectively. The DPPH(•) scavenging activity and reducing power were also higher in decocted extracts. The assayed irradiation doses affected differently the organic acids profile. The levels of total phenolics and flavonoids were lower in the hydromethanolic extracts prepared from samples irradiated at 1 kGy (dose that induced color changes) and in decocted extracts prepared from those irradiated at 8 kGy. The last samples also showed a lower antioxidant activity. In turn, irradiation at 5 kGy favored the amounts of total phenolics and flavonoids. Overall, this study contributes to the understanding of the effects of irradiation in indicators of dwarf mallow quality, and highlighted the decoctions for its antioxidant properties.

Effect of gamma-irradiation on total organic carbon and trihalomethane formation potential

This research was conducted to study the use of radiation in water treatment as an alternative to chlorination which has caused health concerns due to the formation of harmful disinfection by-products. Groundwater solutions from the Biscayne aquifer were radiated with Cobalt-60 gamma radiation and studied for changes in dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), fluorescence and trihalomethane formation potential (THMFP). Molecular fractionations were conducted by ultrafiltration. Effect of the combination of radiation/peroxide was studied for DOC and UV254. Radiation showed significant removal in DOC and THMFP. Similar results were seen in the fluorescence and UV absorbance experiments. Radiation/peroxide did not improve the DOC removal. Radiation of the groundwater samples broke the larger molecular weight fractions in to smaller fractions.

Enhancement of the total phenolic compounds and antioxidant activity of aqueous Citrus limon L. pomace extracts using microwave pre-treatment on the dry powder

The effect of microwave pre-treatment on the levels of total phenolic compounds, flavonoids, proanthocyanidins and individual major compounds as well as the total antioxidant activity of the dried lemon pomace was investigated. The results showed that microwave pre-treatment significantly affected all the examined parameters. The total phenolic content, total flavonoids, proanthocyanidins, as well as the total antioxidant activity significantly increased as the microwave radiation time and power increased (e.g., 2.5 folds for phenolics, 1.4 folds for flavonoids and 5.5 folds for proanthocyanidins), however irradiation more than 480 W for 5 min resulted in the decrease of these parameters. These findings indicate that microwave irradiation time and power may enhance higher levels of the phenolic compounds as well as the antioxidant capacity of the dried lemon pomace powder. However, higher and longer irradiation may lead to a degradation of phenolic compounds and lower the antioxidant capacity of the dried lemon pomace.

Temperature-averaged and total free-free Gaunt factors for κ and Maxwellian distributions of electrons

Aims. Optically thin plasmas may deviate from thermal equilibrium and thus, electrons (and ions) are no longer described by the Maxwellian distribution. Instead they can be described by κ-distributions. The free-free spectrum and radiative losses depend on the temperature-averaged (over the electrons distribution) and total Gaunt factors, respectively. Thus, there is a need to calculate and make available these factors to be used by any software that deals with plasma emission. Methods. We recalculated the free-free Gaunt factor for a wide range of energies and frequencies using hypergeometric functions of complex arguments and the Clenshaw recurrence formula technique combined with approximations whenever the difference between the initial and final electron energies is smaller than 10−10 in units of z2Ry. We used double and quadruple precisions. The temperature- averaged and total Gaunt factors calculations make use of the Gauss-Laguerre integration with 128 nodes. Results. The temperature-averaged and total Gaunt factors depend on the κ parameter, which shows increasing deviations (with respect to the results obtained with the use of the Maxwellian distribution) with decreasing κ. Tables of these Gaunt factors are provided.