The purpose of this research is to determine the feasibility of introducing the Monte Carlo (MC) dose calculation algorithm into the clinical practice. Unlike the Ray Tracing (RT) algorithm, the MC algorithm is not affected by the tissue inhomogeneities, which are significant inside the chest cavity. A retrospective study was completed for 102 plans calculated using both the RT and MC algorithms. The D95 of the PTV was 26% lower for the MC calculation. The first parameter of conformality, as defined as the ratio of the Prescription Isodose Volume to the PTV Volume was on average 1.27 for RT and 0.67 for MC. The results confirm that the RT algorithm significantly overestimates the dosages delivered confirming previous analyses. Correlations indicate that these overestimates are largest for small PTV and/or when the ratio of the volume of lung tissue to the PTV approaches 1. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

The purpose of this thesis is to validate the Monte Carlo algorithm for electron radiotherapy in the Eclipse™ treatment planning system (TPS), and to compare the accuracy of the Electron Monte Carlo algorithm (eMC) to the Pencil Beam algorithm (PB) in Eclipse™. Dose distributions from GafChromic™ EBT3 film measurements were compared to dose distributions from eMC and PB treatment plans. Measurements were obtained with 6MeV, 9MeV, and 12MeV electron beams at various depths. A 1 cm thick solid water template with holes for bone-like and lung-like plugs was used to create assorted configurations and heterogeneities. Dose distributions from eMC plans agreed better with the film measurements based on gamma analysis. Gamma values for eMC were between 83%-99%, whereas gamma values for PB treatment plans were as low as 38.66%. Our results show that using the eMC algorithm will improve dose accuracy in regions with heterogeneities and should be considered over PB. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Motivated by the need to standardize preclinical imaging for image-guided radiation therapy (IGRT), we examine the parameters that influence microcomputed tomography (microCT) scans in the realm of image quality and absorbed dose to tissue, including therapy beam measurements of small fields. Preclinical radiation research aims to understand radiation-induced effects in living tissues to improve quality of life. Small targets and low kilovoltage x-rays create challenges that do not arise in clinical radiation therapy. Evidence based on our multi-institutional study reveals a considerable aberration in microCT image quality from one institution to the next. We propose the adoption of recommended tolerance levels to provide a baseline for producing satisfactory and reproducible microCT image quality scans for accurate dose delivery in preclinical IGRT. Absorbed dose imparted by these microCT images may produce deterministic effects that can negatively influence a radiobiological study. Through Monte Carlo (MC) methods we establish absorbed microCT imaging dose to a variety of tissues and murine sizes for a comprehensive combination of imaging parameters. Radiation beam quality in the small confines of a preclinical irradiator is also established to quantify the effects of beam scatter on half-value layer measurements. MicroCT scans of varying imaging protocols are also compared for murine subjects. Absorbed imaging dose to tissues are established and presented alongside their respective microCT images, providing a visual bridge to systematically link image quality and imaging dose. We then characterize a novel small plastic scintillating dosimeter to experimentally measure microCT imaging and therapy beams in real-time. The presented scintillating dosimeter is specifically characterized for the low energies and small fields found in preclinical research. Beam output is measured for small fields previously only achievable using film. Finally, quality assurance tests are recommended for a preclinical IGRT unit. Within this dissertation, a narrative is presented for guiding preclinical radiotherapy towards producing high quality microCT images with an understanding of the absorbed imaging dose deposited to tissues, including providing a tool to measure small radiation fields. / Graduate

<p>Digital tomosynthesis (DTS) is a quasi-three-dimensional (3D) imaging technique which reconstructs images from a limited angle of cone-beam projections with shorter acquisition time, lower imaging dose, and less mechanical constraint than full cone-beam CT (CBCT). However, DTS images reconstructed by the conventional filtered back projection method have low plane-to-plane resolution, and they do not provide full volumetric information for target localization due to the limited angle of the DTS acquisition. </p><p>This dissertation presents the optimization and clinical implementation of image guided radiation therapy using limited-angle projections.</p><p>A hybrid multiresolution rigid-body registration technique was developed to automatically register reference DTS images with on-board DTS images to guide patient positioning in radiation therapy. This hybrid registration technique uses a faster but less accurate static method to achieve an initial registration, followed by a slower but more accurate adaptive method to fine tune the registration. A multiresolution scheme is employed in the registration to further improve the registration accuracy, robustness and efficiency. Normalized mutual information is selected as the criterion for the similarity measure, and the downhill simplex method is used as the search engine. This technique was tested using image data both from an anthropomorphic chest phantom and from head-and-neck cancer patients. The effects of the scan angle and the region-of-interest size on the registration accuracy and robustness were investigated. The average capture ranges in single-axis simulations with a 44° scan angle and a large ROI covering the entire DTS volume were between -31 and +34 deg for rotations and between -89 and +78 mm for translations in the phantom study, and between -38 and +38 deg for rotations and between -58 and +65 mm for translations in the patient study.</p><p>Additionally, a novel limited-angle CBCT estimation method using a deformation field map was developed to optimally estimate volumetric information of organ deformation for soft tissue alignment in image guided radiation therapy. The deformation field map is solved by using prior information, a deformation model, and new projection data. Patients' previous CBCT data are used as the prior information, and the new patient volume to be estimated is considered as a deformation of the prior patient volume. The deformation field is solved by minimizing bending energy and maintaining new projection data fidelity using a nonlinear conjugate gradient method. The new patient CBCT volume is then obtained by deforming the prior patient CBCT volume according to the solution to the deformation field. The method was tested for different scan angles in 2D and 3D cases using simulated and real projections of a Shepp-Logan phantom, liver, prostate and head-and-neck patient data. Hardware acceleration and multiresolution scheme are used to accelerate the 3D estimation process. The accuracy of the estimation was evaluated by comparing organ volume, similarity and pixel value differences between limited-angle CBCT and full-rotation CBCT images. Results showed that the respiratory motion in the liver patient, rectum volume change in the prostate patient, and the weight loss and airway volume change in the head-and-neck patient were accurately estimated in the 60° CBCT images. This new estimation method is able to optimally estimate the volumetric information using 60-degree projection images. It is both technically and clinically feasible for image-guidance in radiation therapy.</p> / Dissertation

<p>Based on the compressed sensing theorem, we present the integrated software and hardware platform for developing a total-variation based image restoration algorithm by applying prior image information and free-form deformation fields for image guided therapy. The core algorithm we developed solves the image restoration problem for handling missing structures in one image set with prior information, and it enhances the quality of the image and the anatomical information of the volume of the on-board computed tomographic (CT) with limited-angle projections. Through the use of the algorithm, prior anatomical CT scans were used to provide additional information to help reduce radiation doses associated with the improved quality of the image volume produced by on-board Cone-Beam CT, thus reducing the total radiation doses that patients receive and removing distortion artifacts in 3D Digital Tomosynthesis (DTS) and 4D-DTS. The proposed restoration algorithm enables the enhanced resolution of temporal image and provides more anatomical information than conventional reconstructed images.</p><p>The performance of the algorithm was determined and evaluated by two built-in parameters in the algorithm, i.e., B-spline resolution and the regularization factor. These parameters can be adjusted to meet different requirements in different imaging applications. Adjustments also can determine the flexibility and accuracy during the restoration of images. Preliminary results have been generated to evaluate the image similarity and deformation effect for phantoms and real patient's case using shifting deformation window. We incorporated a graphics processing unit (GPU) and visualization interface into the calculation platform, as the acceleration tools for medical image processing and analysis. By combining the imaging algorithm with a GPU implementation, we can make the restoration calculation within a reasonable time to enable real-time on-board visualization, and the platform potentially can be applied to solve complicated, clinical-imaging algorithms.</p> / Dissertation

<p>A bench-top dual cone-beam computed tomography (CBCT) system was developed consisting of two orthogonally placed 40x30 cm<super>2</super> flat-panel detectors and two conventional X-ray tubes with two individual high-voltage generators sharing the same rotational axis. The X-ray source to detector distance is 150 cm and X-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200° of rotation. The dual CBCT (DCBCT) system utilized 110° of projection data from one detector and 90° from the other while the two individual single CBCTs utilized 200° data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum and CT number linearity. The uniformity, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems.</p><p>Compared with single CBCT, the DCBCT presented: 1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125 and 150 kVp); 2) comparable or slightly better contrast to noise ratio (CNR) for low-contrast objects and comparable contrast for high-contrast objects; 3) comparable spatial resolution; 4) comparable CT number linearity with R<super>2</super> &#8805; 0.99 for all four tested energies; 5) lower noise power spectrum in magnitude. DCBCT images of the skull phantom and the ham demonstrated both high-contrast resolution and good soft-tissue contrast.</p><p>One of the major challenges for clinical implementation of four-dimensional (4D) CBCT is the long scan time. To investigate the 4D imaging capabilities of the DCBCT system, motion phantom studies were conducted to validate the efficiency by comparing 4D images generated from 4D-DCBCT and 4D-CBCT. First, a simple sinusoidal profile was used to confirm the scan time reduction. Next, both irregular sinusoidal and patient-derived profiles were used to investigate the advantage of temporally correlated orthogonal projections due to a reduced scan time. Normalized mutual information (NMI) between 4D-DCBCT and 4D-CBCT was used for quantitative evaluation.</p><p>For the simple sinusoidal profile, the average NMI for ten phases between two single 4D-CBCTs was 0.336, indicating the maximum NMI that can be achieved for this study. The average NMIs between 4D-DCBCT and each single 4D-CBCT were 0.331 and 0.320. For both irregular sinusoidal and patient-derived profiles, 4D-DCBCT generated phase images with less motion blurring when compared with single 4D-CBCT.</p><p>For dual kV energy imaging, we acquired 80kVp projections and 150 kVp projections, with an additional 0.8 mm tin filtration. The virtual monochromatic (VM) technique was implemented, by first decomposing these projections into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of the VM CBCT on metal artifact reduction was evaluated with an in-house titanium-BB phantom. The optimal VM energy to maximize CNR for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The linearly-mixed (LM) technique was implemented by linearly combining the low- (80kVp) and high-energy (150kVp) CBCTs. The dose partitioning between low- and high-energy CBCTs was varied (20%, 40%, 60% and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125 and 150kVp.</p><p>The VM technique showed a substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared with a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference in average noise levels measured in the phantom background was 1.2% for dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning were better than those of 150 kVp single-energy CBCTs. The average CNRs for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low contrast objects improved as dose partitioning was more heavily weighted towards low-energy (80kVp) for LM CBCTs.</p><p>For application of the dual-energy technique in the kilovoltage (kV) and megavoltage (MV) range, we acquired both MV projections (from gantry angle of 0° to 100°) and kV projections (90° to 200°) with the current orthogonal kV/MV imaging hardware equipped in modern linear accelerators, as gantry rotated a total of 110°. A selected range of overlap projections between 90° to 100° were then decomposed into two material projections using experimentally determined parameters from orthogonally stacked aluminum and acrylic step-wedges. Given attenuation coefficients of aluminum and acrylic at a predetermined energy, one set of VM projections could be synthesized from two corresponding sets of decomposed projections. Two linear functions were generated using projection information at overlap angles to convert kV and MV projections at non-overlap angles to approximate VM projections for CBCT reconstruction. The CNRs were calculated for different inserts in VM CBCTs of a CatPhan phantom with various selected energies and compared with those in kV and MV CBCTs. The effect of overlap projection number on CNR was evaluated. Additionally, the effect of beam orientation was studied by scanning the CatPhan sandwiched with two 5 cm solid-water phantoms on both lateral sides and an electronic density phantom with two metal bolt inserts.</p><p>Proper selection of VM energy (30keV and 40keV for low-density polyethylene (LDPE), polymethylpentene (PMP), 2MeV for Delrin) provided comparable or even better CNR results as compared with kV or MV CBCT. An increased number of overlap between kV and MV projections demonstrated only marginal improvements of CNR for different inserts (with the exception of LDPE) and therefore one projection overlap was found to be sufficient for the CatPhan study. It was also evident that the optimal CBCT image quality was achieved when MV beams penetrated through the heavy attenuation direction of the object. </p><p>In conclusion, the performance of a bench-top DCBCT imaging system has been characterized and is comparable to that of a single CBCT. The 4D-DCBCT provides an efficient 4D imaging technique for motion management. The scan time is reduced by approximately a factor of two. The temporally correlated orthogonal projections improved the image blur across 4D phase images. Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared with single-energy CBCT acquired with equivalent dose. A novel technique was developed to generate VM CBCTs from kV/MV projections. This technique has the potential to improve CNR at selected VM energies and to suppress artifacts at appropriate beam orientations.</p> / Dissertation

The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.

The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.

PURPOSE: Thermal ablation therapy is an emerging local cancer treatment to destroy cancer tissue using heat. However variations in blood flow and energy absorption rates make it extremely challenging to monitor thermal changes. Insufficient ablation may lead to recurrence of the cancer while excessive ablation may damage adjacent healthy tissues. Ultrasound could be a convenient and inexpensive imaging modality for real-time monitoring of the ablation. For the development and optimization of these methods, it is essential to have ground truth data and a reliable and quantitative validation technique before beginning clinical trials on humans. In this dissertation, my primary focus was to solve the image-to-physical space registration problem using stereotactic fiducials that provide accurate correlation of ultrasound and pathology (ground truth) images. METHOD: A previously developed validation test-bed prototype was evaluated using phantom experiments to identify the shortcomings and limitations. In order to develop an improved validation platform, a simulator was implemented for evaluating registration methods as well as different line fiducial structures. New fiducial line structures were proposed, and new methods were implemented to overcome the limitations of the old system. The new methods were then tested using simulation results and phantom studies. Phantom experiments were conducted to improve the visibility of fiducials, as well as the quality of acquired ultrasound and pathology image datasets. RESULTS: The new system outperforms the previous one in terms of accuracy, robustness, and simplicity. The new registration method is robust to missing fiducials. I also achieved complete fiducial visibility in all images. Enhancing the tissue fixation medium improved the ultrasound data quality. The quality of pathology images were improved by a new imaging method. Simulation results show improvement in pose recovery accuracy using my proposed fiducial structure. This was validated by phantom studies reducing spatial misalignment between the US and pathology image sets. CONCLUSION: A new generation of test-bed was developed that provides a reliable and quantitative validation technique for evaluating and optimizing ablation monitoring methods. / Thesis (Master, Computing) -- Queen's University, 2011-09-29 20:31:55.159

The identification of eloquent areas is of utmost importance in the surgery of tumors located near speech-eloquent brain areas, since the classical concept of a constant localization was proven to be untrue and the spatial localization of these areas may show large interindividual differences. Some neurosurgical centers apply intraoperative electrophysiological methods that, however, necessitate the performance of surgery in the awake patient. This might be a severe burden both for the patient and the operating team in a procedure that lasts several hours; in addition, electrical stimulation may generate epileptic seizures. Alternatively, methods of functional brain imaging (e.g., PET, fMRI, MEG) may be applied, which allow individual localization of speech-eloquent areas. Matching of these image data with a conventional 3D-CT or MRI now allows the exact transfer of this information into the surgical field by neuronavigation. Whereas standards concerning electrophysiological stimulation techniques that could prevent a permanent postoperative worsening of language are available, until now it remains unclear whether the resection of regions shown to be active in functional brain imaging will cause a permanent postoperative deficit. / Die Identifikation sprachaktiver Areale ist von höchster Bedeutung bei der Operation von Tumoren in der Nähe des vermuteten Sprachzentrums, da das klassische Konzept einer konstanten Lokalisation des Sprachzentrums sich als unrichtig erwiesen hat und die räumliche Ausdehnung dieser Areale eine hohe interindividuelle Varianz aufweisen kann. Einige neurochirurgische Zentren benutzen deshalb intraoperativ elektrophysiologische Methoden, die jedoch eine Operation am wachen Patienten voraussetzen. Dies kann sowohl für den Patienten als auch das Operations-Team eine schwere Belastung bei diesem mehrstündigen Eingriff darstellen, zusätzlich können epileptische Anfälle durch die elektrische Stimulation generiert werden. Alternativ können Modalitäten des «functional brain imaging» (PET, fMRT, MEG usw.) eingesetzt werden, die die individuelle Lokalisation sprachaktiver Areale gestatten. Die Bildfusion dieser Daten mit einem konventionellen 3D-CT oder MRT erlaubt den exakten Transfer dieser Daten in den OP-Situs mittels Neuronavigation. Während Standards bei elektrophysiologischen Stimulationstechniken existieren, die eine permanente postoperative Verschlechterung der Sprachfunktion weitgehend verhindern, bleibt die Relevanz sprachaktiver Areale bei den neuesten bildgebenden Techniken bezüglich einer Operations-bedingten Verschlechterung der Sprachfunktion bisher noch unklar. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.