Design of a generally applicable abdominal shield for reducing fetal dose during radiotherapy of common malignancies in pregnant patients

Background: In most cancer cases, the treatment choice for a pregnant patient is radiotherapy. In these patients, the abdomen is usually not exposed; therefore fetus exposure is due to peripheral dose (PD). The purpose of this study was to estimate the fetal dose (the maximum PD in each pregnancy stage) for modalities available and to fabricate and evaluate a generally applicable fetal shield. Materials and Methods: PD values were measured for brain, breast and mediastinum irradiation in a whole body anthropomorphic phantom using a NE 2571 ionization chamber. An external shield was then designed to reduce the fetal dose to the standard dose limit, 5 mSv. Results: The range of PD values as a function of distance from the field’s edge were as follows 1) 9.4-259 cGy for Mantel field; 2) 6.5-95 cGy for chest wall irradiation with 10 MeV electrons, 3) 8.5- 52.5 cGy for tangential field with Co-60 and 4) 4.8-7.8 cGy for brain radiotherapy with 9 MV photon. PD values for the same setups using the fetal shield were as follows: 1) 1.4-22 cGy, 2) 0.5-4 cGy, 3) 1.5-5 cGy and 4) under 1 cGy. Conclusions: The measured PD data sets can be used to estimate fetal dose for specific treatment setups and pregnancy stages. The use of external shield designed in this research reduced the fetal dose effectively to under the threshold (a 70-90% reduction), except for the final stages of pregnancy in Hodgkin’s patients

DOES IN VIVO LIGAMENT FORCE PASS THROUGH LIGAMENT INSERTIONS?: A ROBOTIC STUDY

INTRODUCTION Post traumatic osteoarthritis (PTOA) is a subset of osteoarthritis that arises after traumatic joint injury. Approximately half of patients suffering from anterior cruciate ligament (ACL) injuries have been shown to progress towards PTOA within fifteen years[1]. One of the areas of research for PTOA is examining the biomechanical changes following an ACL injury. A recent study[2] examined the effects of ACL transection (ACLx) in an ovine model. In vivo stifle joint motions were recorded, and recreated in vitro using a novel robotic testing platform. Joint and tissue loads were simultaneously recorded during reproduction of in vivo joint motion[2]. This novel approach was shown to be able to reproduce in vivo motions within less than 0.1° and 0.1mm[2].   The main objective of the present study was to determine if in vivo ligament forces, obtained using the principle of superposition, pass through respective ligament insertional footprints. This study evaluated the accuracy of the measured ligament forces, as they should pass through their bony insertions. This accuracy was examined for medial and lateral collateral ligaments (MCL and LCL), and posterior cruciate ligament (PCL) in ACLx sheep.   METHODS Stifle joints from N=4 sheep that had been previously examined in ACLx kinematics studies were digitized using a coordinate measuring machine. The ligament insertional areas were thoroughly recreated in 3D space, along with the spatial position of the kinematic measurement device. Anatomic coordinate systems were defined on the femur and the tibia. These data were then exported to MATLAB scripts for further analysis. The ligament insertional areas were approximated as planes using least squares regression technique. The intersection of the ligament force vectors with the plane approximations were then calculated. The direction of a ligament force was deemed accurate if the distance between the calculated intersection and footprint centroid was within a determined threshold. A preliminary threshold was calculated as the maximum distance between the centroid and measured points of the footprint. RESULTS Analysis of the data indicated that the technique increases in accuracy for high ligament loads (Figure 1). That is to say as the ligament loads increase, the intersection-centroid distance is reduced. For lower ligament loads (mainly within the “toe” region of the ligament force-displacement behavior), however, the method requires further refinement. DISCUSSION AND CONCLUSIONS This study indicated that the method requires further refinement based on the limitations induced currently. Preliminary data shows that accuracy increases as ligament load magnitudes increase as well. Finding the intersections on plane approximations of the insertional footprints can lead to very large error when the planes approach a parallel state. In these states, a small angular change in force direction can cause a very large change in intersection-centroid distance. Each ligament and its insertions have different functions and geometries, and as such require separate limitations. Future studies would require modifications to the analysis method to account for the limitations involved with the current method

Out-of-field beam characteristics of a 6 MV photon beam: Results of a Monte Carlo study

Detailed characteristics of particles in the periphery of a 6 MV photon beam resulting from the exposure of a water phantom were analyzed. The characteristics at the periphery were determined with respect to particles’ origin and charge, using Monte Carlo simulations. Results showed that in the peripheral regions, the energy fluence and the mean energy distribution of particles are independent of depth, and the majority of charged particles originate in the irradiated volume. The results are used to examine out-of-field dosimetry factors

MicroRNAs in haematopoietic stem cell transplantation outcome

PhD ThesisAllogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for numerous haematological malignancies. Graft-versus-host disease (GVHD) is the major complication causing mortality and is classified into acute (aGVHD) and chronic. MicroRNAs play a significant role in inflammation and have reported potential as biomarkers of different diseases. This study has investigated the role of microRNAs in allo-HSCT outcomes and had two main aims; (1) identification of microRNAs specific to the aGVHD target organ, skin and (2) an investigation into the role of immune specific miRNAs (miR-146a and miR-155) in peripheral blood. Initially, pathway mining was performed on a list of 18 genes that were shown previously, to have deregulated expression levels with regards to GVHD. The pathway mining identified specific immunological pathways in relation to the genes and potential microRNA targets. Global microRNA profiling was performed on a discovery cohort that identified a signature microRNA list in skin biopsies obtained from patients at the time of cutaneous histopathological aGVHD onset (grades I-III) and healthy volunteers. Twelve microRNAs were selected for further validation and it was shown that miR-34a-5p, miR-34a-3p, miR-503-5p and let-7c-5p were elevated and significantly involved in allo-HSCT outcomes. There was an interaction between miR-34a-3p and miR-503-5p which was significantly diagnostic of aGVHD and let-7c-5p was significantly predictive of disease relapse. MiR-34a-5p protein targets; p53 and c-Myc were then evaluated in the same cohort. MiR-34a-5p expression levels and cells stained positively for p53 were significantly correlated in the epidermis. Preliminary optimization of miR-34a-5p knockdown study was successfully conducted which showed promising results in the reduction of T cell proliferation. The whole blood study showed that miR-146a-5p and its interaction with miR-155-5p was predictive of aGVHD incidence in pre-disease onset (Day+28) samples. Interestingly, the expression levels of miR-146a-5p and miR-155-5p negatively correlated with SPI1 (PU.1). In conclusion, these investigations showed that (1) the microRNAs studied in this investigation may regulate the expression levels of the selected 18 genes, (2) microRNA expression levels in clinical skin biopsies obtained at the time of aGVHD onset could potentially be used as diagnostic biomarkers for aGVHD and as predictive biomarkers for overall survival as well as relapse and (3) miR-146a-5p and miR-155-5p expression levels in whole blood could be used as predictive biomarkers for aGVHD incidence

The effect of implementing design for six sigma in new service development

Master'sMASTER OF ENGINEERIN

Analyzing Strain in the Ovine Anterior Cruciate Ligament

Osteoarthritis (OA) is the most common joint disorder affecting adults. Relating the mechanics and biology of the knee joint is crucial to understanding the development and progression OA. A key aim of such studies is to determine the structure/function relationship and failure thresholds of the joint tissues, in-vivo. The Anterior Cruciate Ligament (ACL) is of great interest as it is one of the most commonly injured ligaments linked with premature OA. Previous ACL studies have been unable to determine the stresses within the structure, due to absence of reliable methods of measuring the cross-sectional area of the loaded part of the ligament. Purpose: This study aims to evaluate the normal in-vivo stresses within the ACL, by developing a suitable method to measure the loaded area of the ACL. Methods: Ovine stifle joints were used due to morphological and biochemical proximity to human knee joints. Measurements of in-vivo loadings within the ACL were obtained using an instrumented spatial linkage and robotic test system. Two techniques to measure the area of the loaded ACL will be explored: 3D Virtual Reconstruction (3DVR) and Magnetic Resonance Imaging (MRI). 3DVR: The non-loaded part of the ACL was removed. A cloud of points was measured along the surface of the remaining (loaded) part of the ligament and processed to create a 3DVR of the ACL. MRI: Tests (proton density and T2 mapping) will be run on the 9.4T MR to compare structural differences between a loaded and relaxed ligament. Results: 3DVR method produced only a partial surface reconstruction due to the relatively large size of the probe in comparison to the ligament and femorotibial joint space. Differences between loaded and unloaded MRI images will be assessed using a special jig allowing sequential tensioning of the ligament. Conclusions: It was concluded that the partial 3DVR was insufficient to determine the loaded cross- sectional areas along the ligament accurately. The MRI results will be available for examination shortly

Design and Implementation of a Monte Carlo Framework for Assessment of Spoiler Applications in Abutting Electron Fields

Background: Field matching problems in abutting electron fields can be man-aged by using spoilers. Objective: The aim of this study was to design a Monte Carlo framework for the assessment of spoiler application in abutting electron fields. Material and Methods: In this experimental study, a Siemens Primus treatment head was simulated for a 5 MeV electron beam using BEAMnrc, DOSXYZnrc and EGSnrc user codes. Validation of beam model was done by measurement using a MP3-M water tank and a Semi-flex Chamber-31010 (PTW, Freiburg, Germany). An in-house routine was developed to calculate the combined isodose curves result-ing from simulated adjacent fields. The developed framework was analyzed using PMMA and chromium spoilers. Results: The penumbra width increased from 27.5 mm for open fields to 42 mm for PMMA and 40 mm for chromium. The maximum junction dose reduced from 115% for open fields to 107% for PMMA and 108% for chromium. R90 reduced about 6 mm for PMMA and 3 mm for chromium. Uniformity index reduced from 93% to 77% for both spoilers. Surface dose increased from 79% to 89% for PMMA and 88% for chromium. Conclusion: Using spoilers, penumbra width at the surface was increased, size and depth of hot spots as well as the therapeutic range were reduced and dose homo-geneity at the junction of abutting electron fields was improved. For both spoilers, the uniformity index reduced, and surface percent dose increased. The results of this research can be used to optimize dose distribution in electron beam treatment using abutting fields

Evaluation of Therapeutic Properties of a Low Energy Electron Beam Plus Spoiler for Local Treatment of Mycosis Fungoides: A Monte Carlo Study

Background: When using low-energy electron beams for the treatment of skin lesions, such as Mycosis Fungoides (MF), a beam spoiler is used to decrease electron therapeutic depth (R90) while increasing the surface dose. Objective: The aim of this study was to evaluate the characteristics of a 5 MeV electron beam when using a spoiler for the local treatment of MF skin lesions by Monte Carlo (MC) simulation. Methods: A Siemens Primus treatment head and an acrylic spoiler, positioned at the end of applicator, were simulated using BEAMnrc, an EGSnrc user code. The modelled beam was validated by measurement using MP3-M water tank, Roos parallel plate chamber and Semi flex Chamber-31013 (all from PTW, Freiburg, Germany). For different spoiler thicknesses, dose distributions in water were calculated for 2 field sizes and were compared to those for the corresponding open fields. Results: For a 1.3 cm spoiler, therapeutic range changed from 1.5 cm (open field) to 0.5 cm and 0.4 cm for 10 × 10 cm2 and 20 × 20 cm2 field sizes, respectively. Maximum increase in penumbra width was 2.8 and 3.8 cm for 10 × 10 cm2 and 20 × 20 cm2 field sizes, respectively. Maximum increase in bremsstrahlung contamination was %2 in both field sizes. Conclusion: R90 decreased exponentially with increase in spoiler thickness. The effect of field size on penumbra was much larger for spoiled beam compared to the open beam. The results of this research can be applied to optimize the radiation treatment of MF patients in our hospital

Research of changes of the instability of phase frequency characteristic of high-voltage divider of the pressure, connected with non-identity its elements

На основі проведення багаторазових вимірювань визначено реальний розподіл значень ємності конденсаторів високовольтного плеча подільника напруги з допуском відхилення від номіналу, рівним ±5%. Показано, що даний розподіл є асиметричним по відношенню до номінального значення (22нФ). Проведено перенормування отриманого розподілу по відношенню до середнього значення ємності конденсаторів. Досліджується вплив реального розподілу ємностей конденсаторів на нестабільність фазочастотної характеристики високовольтного подільника напруги. Показано, що вплив реального розподілу ємностей конденсаторів з допуском ± 5% на нестабільність ФЧХ подільника є менш вираженим по відношенню до закону нормального розподілу з середнім квадратичним відхиленням, що дорівнює ±5% . Обгрунтовується як прийнятний допуск на відхилення ємності конденсаторів високовольтного плеча ±5%. Зазвичай заданий допуск на відхилення ємностей ±10% призводить до значної нестабільності ФЧХ високовольтного подільника напруги.On the basis of repeated measurements a real distribution of capacity values of condensers of a high-voltage shoulder of a potential divider is defined with the assumed deviation from the nominal, which is equal to ±5%. It is shown that the given distribution is asymmetric in the relation to rating value (22nF). The renormalization of the received distribution was done in the relation to the average capacity value of condensers. The influence of real distribution of condensers capacities on instability of the phase frequency characteristic (PFC) of a high-voltage potential divider is being researched. It is shown that the influence of the real distribution of condensers capacities with the deviation ±5% on instability of PFC of a divider is less expressed in the relation to the law of normal distribution with an average quadratic deviation, equal to ±5%. A deviation of condensers capacity of a high-voltage shoulder ±5% is proved to be acceptable. Usually the set deviation of capacities ±10% leads to unacceptably high instability of PFC of a high-voltage potential divider.На основе проведения многократных измерений определено реальное распределение значений емкости конденсаторов высоковольтного плеча делителя напряжения с допуском отклонения от номинала, равным ±5%. Показано, что данное распределение является асимметричным по отношению к номинальному значению (22нФ). Проведена перенормировка полученного распределения по отношению к среднему значению емкости конденсаторов. Исследуется влияние реального распределения емкостей конденсаторов на нестабильность фазочастотной характеристики высоковольтного делителя напряжения. Показано, что влияние реального распределения емкостей конденсаторов с допуском ±5% на нестабильность ФЧХ делителя является менее выраженным по отношению к закону нормального распределения со средним квадратическим отклонением равным ±5%. Обосновывается в качестве приемлемого допуск на отклонение емкости конденсаторов высоковольтного плеча ±5%. Обычно задаваемый допуск на отклонение емкостей ±10% приводит к значительной нестабильности ФЧХ высоковольтного делителя напряжения