Fast Monte Carlo Simulations for Quality Assurance in Radiation Therapy

Monte Carlo (MC) simulation is generally considered to be the most accurate method for dose calculation in radiation therapy. However, it suffers from the low simulation efficiency (hours to days) and complex configuration, which impede its applications in clinical studies. The recent rise of MRI-guided radiation platform (e.g. ViewRay’s MRIdian system) brings urgent need of fast MC algorithms because the introduced strong magnetic field may cause big errors to other algorithms. My dissertation focuses on resolving the conflict between accuracy and efficiency of MC simulations through 4 different approaches: (1) GPU parallel computation, (2) Transport mechanism simplification, (3) Variance reduction, (4) DVH constraint. Accordingly, we took several steps to thoroughly study the performance and accuracy influence of these methods. As a result, three Monte Carlo simulation packages named gPENELOPE, gDPMvr and gDVH were developed for subtle balance between performance and accuracy in different application scenarios. For example, the most accurate gPENELOPE is usually used as golden standard for radiation meter model, while the fastest gDVH is usually used for quick in-patient dose calculation, which significantly reduces the calculation time from 5 hours to 1.2 minutes (250 times faster) with only 1% error introduced. In addition, a cross-platform GUI integrating simulation kernels and 3D visualization was developed to make the toolkit more user-friendly. After the fast MC infrastructure was established, we successfully applied it to four radiotherapy scenarios: (1) Validate the vender provided Co60 radiation head model by comparing the dose calculated by gPENELOPE to experiment data; (2) Quantitatively study the effect of magnetic field to dose distribution and proposed a strategy to improve treatment planning efficiency; (3) Evaluate the accuracy of the build-in MC algorithm of MRIdian’s treatment planning system. (4) Perform quick quality assurance (QA) for the “online adaptive radiation therapy” that doesn’t permit enough time to perform experiment QA. Many other time-sensitive applications (e.g. motional dose accumulation) will also benefit a lot from our fast MC infrastructure

MONTE CARLO MODELING BASED PATIENT DOSE OPTIMIZATION IN DIAGNOSTIC RADIOLOGY

Radiation doses are caused by the energy deposited in unit mass of matter from ionizing radiation. In the US, radiation doses from medical imaging increased six-fold in the past generation. Among medical exposures to patients, computed tomography (CT) composes about half of the collective doses, and interventional fluoroscopy composes 14%. Radiation exposure to patients undergoing diagnostic radiological procedures causes increased lifetime carcinogenic risks, especially for pediatric patients who are more radiosensitive than adults. The correlation between procedural x-ray techniques and the radiation doses to patients, as well as the resultant image quality, is not well understood, and therefore the focus of the performed studies. High radiation dose levels can occur as an outcome of complex procedures requiring additional imaging, or when a patient undergoes multiple radiological procedures. Accumulated occupational doses, caused by the scattered radiation from the patient to the staff during the procedures, are also of concern. There are many factors that affect the patient radiation doses, such as different combinations of technical parameter settings and patient characteristics. Due to the complexities and time-consuming nature of clinical dose/exposure measurements, the Monte Carlo technique is the only realistic tool to investigate patient doses and occupational exposure. Therefore, the objective of this Dissertation is to investigate the possible optimization methods of the irradiation technical factors in order to lower radiation doses to patients undergoing diagnostic radiological examinations using Monte Carlo algorithm-based software. Our general hypothesis is that incident x-ray photon energy used in a diagnostic radiological procedure can be optimized to reduce patient doses without sacrificing image quality, and therefore can lower radiation-induced lifetime carcinogenic risks for patients. Our results will be valuable for medical physicists to analyze dose distributions, and for the cardiology clinicians to maximize image guidance capabilities while minimizing potential carcinogenic and deterministic risks to pediatric patients. Firstly, the impact of irradiation parameters on patient doses during CT scans was investigated and possible optimization methods were discussed. Our results about cone beam CT scans showed that there were major differences in organ and effective dose as the x-ray tube rotates around the patient. This suggested that the use of x-ray tube current modulation could produce substantial reductions in organ and effective dose for body imaging with cone beam CT. For chest CT, our results showed that the existing x-ray tube current modulation schemes are expected to reduce patient effective doses in chest CT examinations by about 10%, with longitudinal modulation accounting for two thirds and angular modulation for the remaining one third. It was also shown that the choice of the scanned region affects organ doses in CT. Secondly, the radiation-induced cancer risks from body CT examinations for adult patients were estimated. For patients who differ from a standard sized adult, correction factors based on the patient weight and antero-posterior dimension are provided to adjust organ doses and the corresponding risks. Our results showed that at constant incident radiation intensity, for CT examinations that include the chest, risks in females are markedly higher than those for males, whereas for examinations that include the pelvis, risks in males were slightly higher than those in females. In abdominal CT scans, risks for males and female patients are very similar. A conclusion was reached that cancer risks in body CT can be estimated from the examination Dose Length Product by accounting for sex, age, as well as patient physical characteristics. Thirdly, a set of innovative Monte Carlo models were developed to investigate the role of x-ray photon energy in determining skin dose, energy imparted, and image quality in pediatric interventional radiology using the MCNP5 platform. Contrast, relative noise, and contrast-to-noise ratio (CNR) were obtained for diagnostic imaging with and without the utilization of grids. Our results indicated that using Monte Carlo methods, the optimized x-ray tube voltage for a relatively low patient dose under the desired image quality could be obtained for any specific patient undergoing a certain type of diagnostic examination. Lastly, we investigated the changes in the pattern of energy deposition in patient phantoms following the use of iodinated contrast media using Monte Carlo models built on MCNP5 platform. Relative energy imparted to the volume of interest with iodine contrast agent, as well as to the whole patient phantom, was calculated. Changes in patterns of energy deposition around the contrast-filled volume were also investigated. Our results suggested that adding iodine can result in values of localized absorbed dose increasing by more than an order of magnitude, but the total energy deposition is generally very modest. Furthermore, our results also showed that adding iodine primarily changes the pattern of energy deposition in the irradiated region, rather than increasing the corresponding patient doses. The goal of this project was to establish a better understanding of the roles of different technique factors in the patient doses from diagnostic radiological procedures. Based on these studies, the limitations of the current Monte Carlo software were analyzed and our own Monte Carlo model was proposed for simulations of patient doses during pediatric interventional radiology procedures. The ultimate goal of this study is to develop a comprehensive dosimetry database using Monte Carlo technique, with the output of patient doses, operator doses, and the corresponding radiation-induced carcinogenesis risks for pediatric interventional radiology procedures

COMPARISON OF A PATIENT-SPECIFIC COMPUTED TOMOGRAPHY ORGAN DOSE SOFTWARE WITH COMMERCIAL PHANTOM-BASED TOOLS

Computed Tomography imaging is an important diagnostic tool but carries some risk due to radiation dose used to form the image. Currently, CT scanners report a measure of radiation dose for each scan that reflects the radiation emitted by the scanner, not the radiation dose absorbed by the patient. The radiation dose absorbed by organs, known as organ dose, is a more relevant metric that is important for risk assessment and CT protocol optimization. Tools for rapid organ-dose estimation are available but are limited to using general patient models. These publicly available tools are unable to model patient-specific anatomy and positioning within the scanner. To address these limitations, the Personalized Rapid Estimator of Dose in Computed Tomography (PREDICT) dosimetry tool was recently developed. This study validated the organ doses estimated by ‘PREDICT’ with ground truth values. The patient-specific PREDICT performance was also compared to two publicly available phantom-based methods: VirtualDose and NCICT. The PREDICT tool demonstrated lower organ dose errors compared to the phantom-based methods, demonstrating the benefit of patient-specific modeling. This study also developed a method to extract the walls of cavity organs, such as the bladder and the intestines, and quantified the effect of organ wall extraction on organ dose. The study found that the exogenous material within the cavity organ can affect organ dose estimate, therefore demonstrating the importance of boundary wall extraction in dosimetry tools such as PREDICT

Study of dosimetry techniques applied to electron beams with high dose rate

Tese de mestrado, Engenharia Física, 2023, Universidade de Lisboa, Faculdade de CiênciasElectron beams of 4-20 MeV are used for Total Skin Electron Irradiation (TSEI) of T-cell lymphomas like the mycosis fungoides type. High dose rate electron (HDRE) beams show effectiveness in achieving local control rates close to 100% and low rates of acute and late toxicity. An Elekta Infinity Agility machine was modeled without manufacturer information and the resulting 6 MeV (TSEI compatible energy) beam was compared with reference experimental beam. The dosimetric study was conducted using Advanced Markus® Type 34045 plane-parallel ionization chamber (IC) and GafChromicTM EBT-XD films. Both water (MP3) and solid water (RW3) were used, and beam evaluation involved reference 10x10 cm2 fields and 100 cm SSD as well as open fields and 240 cm SSD TSEI compatible. Functional performance testing was done for evaluation of beam constancy in HDRE operating mode. Results show a 0.983 Gy per 100 MU in reference conditions and a 9.115 times higher dose using HDRE mode. Gamma analysis passing of 100 % (2 mm DTA / 2 % DD) was obtained, for comparison between MP3 and RW3 HDRE beams in an open field configuration and for an SSD of 100 cm. The working range was within the effective range of EBTXD films. On a 240 cm spaced perpendicular plane, relative dose was verified as symmetrical within a 15 % tolerance. In an anthropomorphic phantom, dose was analyzed using the dual-field Stanford technique and dmax shift was seen to occur, discarding interface artifacts, from 1.40 ± 0.05 cm (SSDref) to 0.7 ± 0.2 cm. From TOPAS MC simulation, gamma analysis has shown that the model agrees completely with reference beam. Limited agreement was seen using SSD of 240 cm. MC model mimics the studied linac using reference conditions and SSD of 240 cm is adequate for TSEI implementation. More studies for confirmation of results and others focusing on non-reference conditions are needed

Review on electrical impedance tomography: Artificial intelligence methods and its applications

© 2019 by the authors. Electrical impedance tomography (EIT) has been a hot topic among researchers for the last 30 years. It is a new imaging method and has evolved over the last few decades. By injecting a small amount of current, the electrical properties of tissues are determined and measurements of the resulting voltages are taken. By using a reconstructing algorithm these voltages then transformed into a tomographic image. EIT contains no identified threats and as compared to magnetic resonance imaging (MRI) and computed tomography (CT) scans (imaging techniques), it is cheaper in cost as well. In this paper, a comprehensive review of efforts and advancements undertaken and achieved in recent work to improve this technology and the role of artificial intelligence to solve this non-linear, ill-posed problem are presented. In addition, a review of EIT clinical based applications has also been presented

A multi-compartmental mathematical model of the postprandial human stomach : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Anatomy and Physiology at Massey University, Palmerston North, New Zealand

Computational fluid dynamics of the human stomach helps to understand the gastric processes such as trituration, mixing, and transit of digesta. Their outcomes give greater insight into the design of food and orally dosed drug delivery system. Current models of gastric contractile activity are primarily limited to the gastric antrum and assume global values for the various physiological characteristics. This thesis developed a unified compartmental gastric model with correctly informed anatomical and physiological data. The gastric geometry incorporated the actions of multiple compartments, such as the gastric fundus, body, antrum, pyloric canal, proximal duodenal cap, and the small intestinal brake. Lattice-Boltzmann Method (LBM) is used to simulate the fluid dynamics within the stomach. This thesis quantified the effects of transgastric pressure gradient (TGPG) between the fundus and the duodenum, the effect of antral propagating contraction (APC) amplitude, and the viscosity of the gastric contents on gastric flow, mixing, and gastric emptying. The results of this work suggest that TGPG influences gastric emptying where as APCs do not play major role in gastric emptying. Flow rate without TGPG obtained in this work agrees with previous work (Pal et al., 2004); however, it is higher in the presence of a TGPG. Results show that APCs promote recirculation, and the amplitude of APC is vital in this regard. The 'pendulating' flow of gastric content observed in this work is reported previously in duplex sonography experiments (Hausken et al., 1992). This work quantified the gastric shear rates (0.6 - 2.0 /s). This work also suggests that the viscosity of the content influences gastric fluid dynamics. This work is a simplified first step towards a 3D gastric model. Hence, these simulation studies were performed under two simplifications: dimensionality and rheology, i.e., we have assumed a Newtonian fluid flow in 2D gastric geometry. A 3D gastric model with more rheologically realistic fluid to explore the pseudoplastic fluid dynamics within the stomach in the future is recommended

Advanced capabilities for planar X-ray systems

Mención Internacional en el título de doctorThe past decades have seen a rapid evolution towards the use of digital detectors in radiology and a more flexible robotized movement of the system components, X-ray tube and detector. This evolution opened the possibility for incorporating advanced capabilities in these planar X-ray systems, and for providing new valuable diagnostic information compared to the previous technology. Some of the current challenges for radiography are to obtain more quantitative images and to reduce the inherent superposition of tissues because of the 2D nature of the technique. Dual energy radiography, based on the acquisition of two images at different source voltages, enables a separate characterization of soft tissue and bone structures. Its benefits over conventional radiography have been proven in different applications, since it improves information content without adding significant extra acquisition time or radiation dose. In a different direction, a really disruptive advance would be to obtain 3D imaging with systems designed just for planar images. The incorporation of tomographic capabilities into these systems would have to deal with the acquisition of a limited number of projections, with non-standard geometrical configurations. This thesis presents original contributions in these two directions: dual energy radiography and 3D imaging with X-ray systems designed for planar imaging. The work is framed in a line of research of the Biomedical Imaging and Instrumentation Group from the Bioengineering and Aerospace Department of University Carlos III de Madrid working jointly with the University Hospital Gregorio Marañón, focused on the advance of radiology systems. This research line is carried out in collaboration with the group of Computer Architecture, Communications and Systems (ARCOS), from the same university, the Imaging Research Laboratory (IRL) of the University of Washington and the research center CREATIS, France. The research has a clear focus on technology transfer to the industry through the company Sedecal, a Spanish multinational among the 10 best world companies in the medical imaging field. The first contribution of this thesis is a complete novel protocol to incorporate dual energy capabilities that enable quantitative planar studies. The proposal is based on the use of a preliminary calibration with a very simple and low-cost phantom formed by two parts that represent soft tissue and bone equivalent materials. This calibration is performed automatically with no strict placement requirements. Compared to current Dual-energy X-ray Absorptiometry (DXA) systems, 1) it provides real mass-thickness values directly, enabling quantitative planar studies instead of relative comparisons, and 2) it is based on an automatic preliminary calibration without the need of interaction of an experienced technician. The second contribution is a novel protocol for the incorporation of tomographic capabilities into X-ray systems originally intended for planar imaging. For this purpose, we faced three main challenges. First, the geometrical trajectory of equipment follows non-standard circular orbits, thus posing severe difficulties for reconstruction. To handle this, the proposed protocol comprises a new geometrical calibration procedure that estimates all the system parameters per-projection. Second, the reconstruction of a limited number of projections from a reduced angular span leads to severe artifacts when using conventional reconstruction methods. To deal with these limited-view data, the protocol includes a novel advanced reconstruction method that incorporates the surface information of the sample, which can be extracted with a 3D light surface scanner. These data are introduced as an imposed constraint following the Split Bregman formulation. The restriction of the search space by exploiting the surface-based support becomes crucial for a complete recovery of the external contour of the sample and surroundings when the angular span is extremely reduced. The modular, efficient and flexible design followed for its implementation allows for the reconstruction of limited-view data with non-standard trajectories. Third, the optimization of the acquisition protocols has not yet explored with these systems. This thesis includes a study of the optimum acquisition protocols that allowed us to identify the possibilities and limitations of these planar systems. Using the surface-constrained method, it is possible to reduce the total number of projections up to 33% and the angular span down to 60 degrees. The contributions of this thesis open the way to provide depth and quantitative information very valuable for the improvement of radiological diagnosis. This could impact considerably the clinical practice, where conventional radiology is still the imaging modality most used, accounting for 80-90% of the total medical imaging exams. These advances open the possibility of new clinical applications in scenarios where 1) the reduction of the radiation dose is key, such as lung cancer screening or Pediatrics, according to the ALARA criteria (As Low As Reasonably Achievable), 2) a CT system is not usable due to movement limitations, such as during surgery or in an ICU and 3) where costs issues complicate the availability of CT systems, such as rural areas or underdeveloped countries. The results of this thesis has a clear application in the industry, since it is part of a proof of concept of the new generation of planar X-ray systems that will be commercialized worldwide by the company SEDECAL (Madrid, Spain).Los últimos años están viendo un rápido avance de los sistemas de radiología hacia el uso de detectores digitales y a una mayor flexibilidad de movimientos de los principales componentes del sistema, el tubo de rayos X y el detector. Esta evolución abre la posibilidad de incorporar capacidades avanzadas en sistemas de imagen plana por rayos X proporcionando nueva información valiosa para el diagnóstico. Dos retos en radiografía son obtener imágenes cuantitativas y reducir la superposición de tejidos debida a la naturaleza proyectiva de la técnica. La radiografía de energía dual, basada en la adquisición de dos imágenes a diferente kilovoltaje, permite obtener imágenes de tejido blando y hueso por separado. Los beneficios de esta técnica que aumenta la cantidad de información sin añadir un tiempo de adquisición o de dosis de radiación extra significativos frente al uso de radiografía convencional, han sido demostrados en diferentes aplicaciones. En otra dirección, un avance realmente disruptivo sería la obtención de imagen 3D con sistemas diseñados únicamente para imagen plana. La incorporación de capacidades tomográficas en estos sistemas tendría que lidiar con la adquisición de un número limitado de proyecciones siguiendo trayectorias no estándar. Esta tesis presenta contribuciones originales en esas dos direcciones: radiografía de energía dual e imagen 3D con sistemas de rayos X diseñados para imagen plana. El trabajo se encuadra en una línea de investigación del grupo de Imagen Biomédica e Instrumentación del Departamento de Bioingeniería e Ingeniería Aerospacial de la Universidad Carlos III de Madrid junto con el Hospital Universitario Gregorio Marañon, centrada en el avance de sistemas de radiología. Esta línea de investigación se desarollada en colaboración con el grupo Computer Architecture, Communications and Systems (ARCOS), de la misma universidad, el grupo Imaging Research Laboratory (IRL) de la Universidad de Washington y el centro de investigación CREATIS, de Francia. Se trata de una línea de investigación con un claro enfoque de transferencia tecnológica a la industria a través de la compañía SEDECAL, una multinacional española de entre las 10 líderes del mundo en el campo de la radiología. La primera contribución de esta tesis es un protocolo completo para incorporar capacidades de energía dual que permitan estudios cuantitativos de imagen plana. La propuesta se basa en una calibración previa con un maniquí simple y de bajo coste formado por dos materiales equivalentes de tejido blando y hueso respectivamente. Comparado con los sistemas actuales DXA (Dual-energy X-ray Absorptiometry), 1) proporciona valores reales de tejido atravesado, 2) se basa en una calibración automática que no requiere la interacción de un técnico con gran experiencia. La segunda contribución es un protocolo nuevo para la incorporación de capacidades tomográficas en sistemas de rayos X originariamente diseñados para imagen plana. Para ello, nos enfrentamos a tres principales dificultades. En primer lugar, las trayectorias que pueden seguir la fuente y el detector en estos sistemas no constituyen órbitas circulares estándares, lo que plantea retos importantes en la caracterización geométrica. Para solventarlo, el protocolo propuesto incluye una calibración geométrica que estima todos los parámetros geométricos del sistema para cada proyección. En segundo lugar, la reconstrucción de un número limitado de proyecciones adquiridas en un rango angular reducido da lugar a artefactos graves cuando se reconstruye con algoritmos convencionales. Para lidiar con estos datos de ángulo limitado, el protocolo incluye un nuevo método avanzado de reconstrucción que incorpora la información de superficie de la muestra, que se puede se obtener con un escáner 3D. Esta información se impone como una restricción siguiendo la formulación de Split Bregman, para compensar la falta de datos. La restricción del espacio de búsqueda a través de la explotación del soporte basado en superficie, es crucial para una recuperación completa del contorno externo de la muestra cuando el rango angular es extremadamente pequeño. El diseño modular, eficiente y flexible de la implementación propuesta permite reconstruir datos de ángulo limitado obtenidos con posiciones de fuente y detector no estándar. En tercer lugar, hasta la fecha, no se ha explorado la optimización del protocolo de adquisición con estos sistemas. Esta tesis incluye un estudio de los protocolos óptimos de adquisición que permitió identificar las posibilidades y limitaciones de estos sistemas de imagen plana. Gracias al método de reconstrucción basado en superficie, es posible reducir el número total de proyecciones hasta el 33% y el rango angular hasta 60 grados. Las contribuciones de esta tesis abren la posibilidad de proporcionar información de profundidad y cuantitativa muy valiosa para la mejora del diagnóstico radiológico. Esto podría impactar considerablemente en la práctica clínica, donde la radiología convencional es todavía la modalidad de imagen más utilizada, abarcando el 80- 90% del total de los exámenes de imagen médica. Estos avances abren la posibilidad de nuevas aplicaciones clínicas en escenarios donde 1) la reducción de la dosis de radiación es clave, como en screening de cáncer de pulmón, de acuerdo con el criterio ALARA (As Low As Reasonably Achievable), 2) no se puede usar un sistema TAC por limitaciones de movimiento como en cirugía o UCI, o 3) el coste limita la disponibilidad de sistemas TAC, como en zonas rurales o en países subdesarrollados. Los resultados de esta tesis presentan una clara aplicación industrial, ya que son parte de un prototipo de la nueva generación de sistemas planos de rayos X que serán distribuidos mundialmente por la compañía SEDECAL.This thesis has been developed as part of several research projects with public funding: - DPI2016-79075-R. ”Nuevos escenarios de tomografía por rayos X”, IP: Mónica Abella García, Ministerio de Economía y Competitividad, 01/01/2017-31/12/2019, 147.620 e. - ”Nuevos escenarios de tomografía por rayos X (NEXT) DPI2016-79075-R. Ministerio de Economía”, Industria y Competitividad. (Universidad Carlos III de Madrid). 30/12/2016-29/12/2019. 147.620 e. (…) - FP7-IMI-2012 (GA-115337), ”PreDict-TB: Model-based preclinical development of anti-tuberculosis drug combinations”. FP7-IMI - Seventh Framework Programme (EC-EFPIA). Unión Europea. (Universidad Carlos III de Madrid). 01/05/2012-31/10/2017. (…) - TEC2013-47270-R, ”Avances en Imagen Radiológica (AIR)”, Ministerio de Economía y Competitividad”, 01/01/2014-31/12/2016. IP: Mónica Abella Garcia and Manuel Desco Menéndez. 160.204 e (…) - RTC-2014-3028-1, ”Nuevos Escenarios Clínicos con Radiología Avanzada (NECRA)”, Ministerio de Economía y Competitividad, 01/06/2014-31/12/2016 IP: Mónica Abella García. 2014-2016. 219.458,96 e - IDI-20130301, ”Nuevo sistema integral de radiografía (INNPROVE: INNovative image PROcessing in medicine and VEterinary)”, IP: Mónica Abella García and Manuel Desco Menéndez. Ministerio de Economía y Competitividad. Subcontratación CDTI, 14/01/2013-31/03/2015. Total: 1.860.629e (UC3M: 325.000e). (Art. 83) - IPT-2012-0401-300000 INNPACTO 2012, ”Tecnologías para Procedimientos Intraoperatorios Seguros y Precisos. XIORT. MINECO. (Universidad Carlos III de Madrid). 01/01/2013-31/12/2015.Programa Oficial de Doctorado en Ingeniería MatemáticaPresidente: Doménec Ros Puig.- Secretario: Cyril Riddell.- Vocal: Yannick Boursie

Theoretical and Experimental Tools for Clinical Translation of Quantitative Tissue Optical Sensing.

Quantitative tissue optical spectroscopy has been considered as a promising method for clinical diagnosis, owing to its ability to non-invasively give an objective assessment of biological tissues at cellular and sub-cellular levels. In spite of recent advances in optics and the computational power, not many quantitative tissue optical sensing technologies have been translated into clinical practice. In order to translate this technology in the clinics, we need to further improve the technology. To name a few, we need accurate and rapid quantification method for a real-time diagnostic feedback. Next, we need computational methods for complex tissue-optics problems. Also, we need a novel approach in probe design for the inaccessible organs. This dissertation focuses on the development, verification and validation of theoretical (mathematical and computational) and experimental (instrumental) tool set to promote the translation of quantitative tissue optical spectroscopy into clinical diagnostic applications. For the mathematical tool, a direct-fit photon tissue interaction (DF-PTI) model that could rapidly and accurately extract the parameters associated biophysical features was developed and validated to characterize the precursor lesions of pancreatic cancer. A rapid scattering model on pancreatic tissue reflectance based on principal components analysis (PCA) results was also developed. The diagnostic capability of scattering properties obtained was demonstrated on an 18-patient data set using a rigorous statistical method, which implied the potential of reflectance spectroscopy for real-time detection of pancreatic cancer. For the computational tool, a ray-traced Monte Carlo (RTMC) simulation for the design of fluorescence spectroscopy or imaging system utilizing complex optics to probe turbid biological tissues was devised. This new method was verified computationally with epithelial tissue models and experimentally using tissue-simulating optical phantoms. For the instrumental tool, the design and development of minimally-invasive diagnostic technologies employing optoelectronic components were discussed. In this dissertation, we focused on detection of pancreatic cancer, which has the worst prognosis among other major cancers. Pancreatic tissues were employed as our model system to validate our developed tools. The developed technology and tools can be applied to a variety of other human tissue sites to help in the translation of quantitative tissue optical sensing in a clinical setting.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111401/1/paulslee_1.pd