A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding.

We investigate via Monte Carlo simulations a new 125I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g-1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g-1 and 66 mg g-1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation.

This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g(-1), which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 µm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles.

Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.

Comprehensive quality assurance phantom for the small animal radiation research platform (SARRP).

PURPOSE: To develop and test the suitability and performance of a comprehensive quality assurance (QA) phantom for the Small Animal Radiation Research Platform (SARRP). METHODS AND MATERIALS: A QA phantom was developed for carrying out daily, monthly and annual QA tasks including: imaging, dosimetry and treatment planning system (TPS) performance evaluation of the SARRP. The QA phantom consists of 15 (60 × 60 × 5 mm(3)) kV-energy tissue equivalent solid water slabs. The phantom can incorporate optically stimulated luminescence dosimeters (OSLD), Mosfet or film. One slab, with inserts and another slab with hole patterns are particularly designed for image QA. RESULTS: Output constancy measurement results showed daily variations within 3%. Using the Mosfet in phantom as target, results showed that the difference between TPS calculations and measurements was within 5%. Annual QA results for the Percentage depth dose (PDD) curves, lateral beam profiles, beam flatness and beam profile symmetry were found consistent with results obtained at commissioning. PDD curves obtained using film and OSLDs showed good agreement. Image QA was performed monthly, with image-quality parameters assessed in terms of CBCT image geometric accuracy, CT number accuracy, image spatial resolution, noise and image uniformity. CONCLUSIONS: The results show that the developed QA phantom can be employed as a tool for comprehensive performance evaluation of the SARRP. The study provides a useful reference for development of a comprehensive quality assurance program for the SARRP and other similar small animal irradiators, with proposed tolerances and frequency of required tests.

A Software App for Radiotherapy with In-situ Dose-painting using high Z nanoparticles.

The purpose of this work is to develop an user friendly and free-to-download application software that can be employed for modeling Radiotherapy with In-situ Dose-painting (RAID) using high-Z nanoparticles (HZNPs). The RAID APP is software program written in Matlab (Mathworks, Natick, MA, USA) based on deterministic code developed to simulate the space-time intra-tumor HZNPs biodistribution within the tumor, and the corresponding dose enhancement in response to low dose rate (LDR) brachytherapy of I-125, Pd-102, Cs-131 and kilovoltage x-rays such as 50 keV and 100 keV. Through the GUI of RAID APP, the user will be directed to different features to compute various parameters related to the dose enhancement and the biodistribution of NPs within high risk tumor sub-volumes. The software was developed as tool for research purposes with potential for subsequent development to guide dose-painting treatment planning using radiosensitizers such as gold (Au) and platinum (Pt).

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator.

PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilovoltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. METHODS: We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multi-channel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm(2). The results were compared against Monte Carlo simulations. RESULTS: Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%-3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. CONCLUSIONS: EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated.

SU-E-T-408: Enhancing Stereotactic Radiosurgery for Neovascular Age-Related Macular Degeneration, Using Gold Nanoparticles.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss for people over the age of 60 in the United States. In this study the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance stereotactic radiosurgery for neovascular AMD is investigated. METHODS: Analytic calculations were carried out to estimate the nucleus dose enhancement factor (nDEF) due to photon-induced photo- /Auger electrons from AuNP targeting neovascular AMD endothelial cells (EC). The nDEF represents the ratio of the dose to the nucleus with and without the presence of AuNP. As in previous studies, the EC is modeled as a slab of 2 µm (thickness) × 10 µm (length) × 10 µm (width) containing a nucleus of 5 µm diameter and thickness of 0.5 - 1 µm. The targeted AuNP are attached to the exterior of the EC. The nDEF was calculated for a range of feasible AuNP local concentrations (1-7 mg/g) using the clinically applicable 100 kVp x-rays employed by the IRayTM system (Oraya Therapeutics Inc. Newark, CA), with total filtration of 0.75 mm Al and 0.8 mm Be. For comparison the nDEF for other energies: 80 kVp, 90 kVp, 110 kVp, and 120 kVp was also investigated. RESULTS: For 100 kVp x-rays, the results revealed nDEF values of 1.30 - 3.26 for the investigated concentration range of 1 - 7 mg/g, respectively. In comparison, for the same concentration range, nDEF values of 1.32 - 3.40, 1.31-3.33, 1.29 - 3.19, 1.28 - 3.12 were calculated for 80 kVp, 90 kVp, 110 kVp, and 120 kVp x-rays, respectively. CONCLUSIONS: The results predict substantial dose enhancement to the sensitive nucleus of neovascular endothelial cells, targeted by AuNP during kilovoltage stereotactic radiosurgery. This suggests that AuNP may be employed as radiosensitizers to enhance therapeutic efficacy during radiosurgery for neovascular AMD.

Advances in phase-sensitive acoustic microscopy studies of polymer blend films: annealing effects and micro-elastic characterization of PS/PMMA blends.

The unique phase-sensitive acoustic microscope is used for the structural and mechanical characterization of thin films of polystyrene/polymethylmethacrylate blends. The effect of annealing on blends of polystyrene/polymethylmethacrylate spin coated from different solvents unto a substrate is studied. Varying the solvents according to vapour pressure and spin coating at different speeds (for thickness variation) led to changes in phase domain distributions and overall structural properties before annealing. Annealing in vacuum at 190 degrees C for 48 h resulted in the elimination of solvent effects with all samples reverting to a similar morphology irrespective of common solvent and thickness. The Young's moduli at specific points on the film (E(polystyrene)= 3.4 +/- 0.3 GPa, E(polymethylmethacrylate)= 4.2 +/- 0.4 GPa) and over a given area (E(polystyrene/polymethylmethacrylate)= 3.9 +/- 0.4 GPa) were determined by combinatory use of the atomic force microscope and phase-sensitive acoustic microscope. These results demonstrate a minimally invasive method for the quantitative characterization of polymer blend films.

Characterization of polymer thin films by phase-sensitive acoustic microscopy and atomic force microscopy: a comparative review.

The potential of phase-sensitive acoustic microscopy (PSAM) for characterizing polymer thin films is reviewed in comparison to atomic force microscopy (AFM). This comparison is based on results from three-dimensional vector contrast imaging and multimodal imaging using PSAM and AFM, respectively. The similarities and differences between the information that can be derived from the AFM topography and phase images, and the PSAM phase and amplitude micrographs are examined. In particular, the significance of the PSAM phase information for qualitative and quantitative characterization of the polymer films is examined for systems that generate surface waves, and those that do not. The relative merits, limitations and outlook of both techniques, individually, and as a complementary pair, are discussed.

Phase-sensitive acoustic microscopy of polymer thin films.

The three-dimensional images obtained by scanning acoustic microscopy with vector contrast (PSAM), contain significant qualitative and quantitative information that is not easily obtainable by other methods. We employ this technique to examine homopolymer and polymer blend thin films. The complex V(z) functions derived from the images, and the results obtained by image processing and meticulous analysis are employed to render the morphology, composition and micro-mechanical properties of the polymer films. In addition, ways by which the information inherent in the phase images can be extracted are examined. This is highly desirable, as the phase images contain very useful additional information.

Cation diffusion in cartilage measured by pulsed field gradient NMR.

In this study, the pulsed field gradient (PFG) nuclear magnetic resonance (NMR) technique was used for the investigation of (1) concentration and compression effects on cation self-diffusion, and (2) restricted diffusion of cations in cartilage. Since physiologically relevant cations like Na+ are difficult to investigate owing to their very short relaxation times, the cations tetramethylammonium (TMA) and tetraethylammonium (TEA) were employed for diffusion studies in samples of explanted cartilage. Results indicated that the diffusion of monovalent cations shows strong similarities to observations already made in studies of the diffusion of water in cartilage: with increasing compression, i.e. decreasing water content, the diffusion coefficient of the cation decreases concomitantly. The diffusion coefficients also showed a decrease with increasing cation concentrations, basically reflecting the corresponding decrease in the water content. Both results could be explained by the well-established model of Mackie and Meares. This, together with the similarity of the diffusion coefficient D in cartilage relative to free solution (about 50%) for both cations, is consistent with the view that the water content and not the charge is the most important determinant of the intratissue diffusivity of monovalent cations. Diffusion studies with increasing observation times showed strong evidence of restricted diffusion, allowing the estimation of the geometry of barriers within cartilage.

[Study of diffusion in cartilage by the "PFG" (pulsed-field gradient NMR) technique]. / Studium der Diffusion im Knorpel mit der "PFG" (pulsed-field-gradient)-NMR-Technik.

Since cartilage does not contain any blood vessels, diffusion is the most important transport mechanism for its supply. Although several methods are available for the measurement of diffusion, this study focuses exclusively on NMR methods. Besides the "classic" water diffusion, the diffusion behaviour of ions and polymers in cartilage is also described. In all cases, and at short observation times, diffusion is mostly determined by the water content of the sample. However, the variation of the observation time allows to obtain information also on the internal structure of cartilage. In addition, it is discussed to which extent the individual techniques allow conclusions with respect to degenerative joint diseases, and under which in vivo conditions they can be applied.