Optical techniques are under exploration to investigate and monitor tissue before, during and after therapies such as laser interstitial thermal therapy and photodynamic therapy. Point radiance spectroscopy reveals a potential wealth of information via directional radiance measurements, compared to isotropic fluence data, in decoupling the absorption and scattering contributions to attenuation. This study extends those findings to spatially heterogeneous systems with an approach that measures local light behaviour directly rather than calculating optical property values. This approach involves identifying chromophores present in local non-homogeneities by characterizing spectral differences in radiance measurements. The method also detects optical asymmetry in the medium by comparing opposing angular spectra. Analysis of the asymmetry can distinguish a homogeneous state from a system that contains a spatial non-homogeneity and identify the side of the radiance probe on which it lies. Monte Carlo simulations reinforce the findings and explain the mechanisms behind trends in sensitivity and capacity.

The structure and composition of articular cartilage and other load-bearing biological tissues are highly complex and heterogeneous. As a result, their functional mechanical properties exhibit clear spatial variations. Unlocking the structure-function relationship in these materials is critical for devising strategies to restore tissue impaired by injury or disease and can provide a template for successful implant design. Here, we describe a tissue deformation imaging stage (TDIS) allowing for simultaneous force measurement and visualization of microscale deformation in soft biological tissues under controlled shear strain. In combination with a fast confocal microscope, the TDIS is used to test the microscale response of articular cartilage to shear loading. To obtain the location-specific shear modulus of this tissue, we employ a high-resolution technique that involves tracking the deformation of a line photobleached into a fluorescently stained sample loaded in the TDIS. We find that the quasi-static and dynamic shear moduli are lowest roughly 100 mum below the articular surface. Here, articular cartilage is highly nonlinear, stiffening under increased shear strain and becoming more compliant under increased compressive strain. Using a simple thought model, we relate these results to structural features of the collagen network in articular cartilage. Furthermore, we demonstrate that the region of maximum compliance is also the primary site of shear energy dissipation in articular cartilage. Our findings suggest that damage to or surgical removal of the surface of this tissue will increase the joint’s susceptibility to shear-induced damage. Finally, similar experiments are performed on intervertebral disc and growth plate, demonstrating the versatility of our in-situ strain mapping techniques.

The purpose of this work was to design and construct a radio-frequency coil optimized for imaging the Optic Nerve (ON) on a Siemens 3T magnetic resonance imaging (MRI) scanner. The specific goals were to optimize signal sensitivity from the orbit to the optic chiasm and improve SNR over designs currently in use. The constructed coil features two fiberglass formers that can slide over each other to accommodate any arbitrary head size, while maintaining close coupling near the eyes and around the head in general. This design eliminates the air void regions that occur between the coil elements and the forehead when smaller heads are imaged in one-piece, nonadjustable coil formers. The 28 coil elements were placed using a soccer-ball pattern layout to maximize head coverage. rSNR profiles from phantom imaging studies show that the ON coil provides approximately 55% greater rSNR at the region of the optic chiasm and approximately 400% near the orbits compared to the 12-channel commercial coil. The improved rSNR in the optic nerve region allows performance of high resolution DTI, which provides a qualitative measurement for evaluating optic neuritis. Images from volunteer and patient studies with the ON coil reveal plaques that correspond well with the patient disease history of chronic bilateral optic neuritis. Correspondence of image findings with patient disease histories demonstrates that optic neuritis can be visualized and detected in patients using 3T MRI with advanced imaging coils, providing improved patient care.

In cancer radiation therapy, the conventional approach has been to calculate and report dose in terms of dose-to-water. With the introduction of commercial Monte Carlo based treatment planning systems, it is now possible to calculate and evaluate dose distributions in terms of dose-to-medium, as opposed to the traditional dose-to-water, of conventional planning systems. The two calculation approaches are conceptually different and the method used has an impact on the reported doses to different organs, such as bone and lung. For electron beams, differences between the two methods have been reported to exceed 10% in cases with hard bone. These differences are greatest in materials whose electron densities are furthest from water, such as bone and lung. This has raised the question of which approach is more appropriate. An AAPM task group has recently recommended that both options should be available in commercial software, but as of yet, there is no consensus which approach should be used. There is a need for systematic analysis of clinical data that would help with the understanding of differences between the Dm and Dw approaches, which in turn could lead to a more accurate evaluation of treatment outcomes. The purpose of this study is to investigate the dosimetric differences between plans calculated using the Dm versus Dw approach for clinical breast, and head and neck cases treated with electron beams. The analysis included plans for epoxy-resin-based phantoms containing hard bone, lung, and air heterogeneities, as well as a retrospective study breast, and head and neck cancer patients treated with electron beams. In some cases, where hard bone was present, differences between Dm and D w exceeded 10%. Differences were consistent with the water-to-tissue stopping power.

We have developed a high sensitivity beta camera with good spatial resolution for use in 18FDG guided surgery. The camera is based on novel photodetectors called silicon photomultipliers SiPMs). These detectors can be employed in the place of photomultiplier tubes PMTs), the current standard for nuclear medicine instrumentation. The SiPM is extremely compact, high gain, insensitive to magnetic fields, and operates at low bias voltage, all of which features are advantageous for an instrument designed for surgical oncology. We have tested various models of SiPMs to evaluate their suitability for this application. We have built a series of beta imagers, the performance of which has improved along with the manufacturing technology. The first two dimensional imaging array was built for proof of principle only； the extremely low form factor of 2.5% led to distortion in the linearity of the spatial response and poor spatial resolution of 15 mm for a 1 mm source. The second design was a linear 1 x 4 array； and two versions were constructed with SiPMs from two different manufacturers. The performance was greatly improved for these arrays, with spatial resolution of about 2 mm for both arrays and sensitivities of 0.28 cps/Bq and 0.15 cps/Bq. The final design discussed in this work was a 17 mm x 17 mm two dimensional array, based on the most recent and best performing SiPMs, with the front-end electronics designed to fit into the handle of a surgical probe. The spatial response was linear for all but the outer 3 mm of the camera and the spatial resolution near the center was 2.0 mm. Sensitivity was determined to be 0.36 cps/Bq. The array performance was evaluated in terms of image contrast with background sources of radiation. The results show that this beta camera should continue to be developed into a clinically implementable instrument.

Advances in Computed Tomography CT) technology have led to an increase in the modalitys diagnostic capabilities and therefore its utilization, which has in turn led to an increase in radiation exposure to the patient population. As a result, CT imaging currently constitutes approximately half of the collective exposure to ionizing radiation from medical procedures. In order to understand the radiation risk, it is necessary to estimate the radiation doses absorbed by patients undergoing CT imaging. The most widely accepted risk models are based on radiosensitive organ dose as opposed to whole body dose. In this research, radiosensitive organ dose was estimated using Monte Carlo based simulations incorporating detailed multidetector CT MDCT) scanner models, specific scan protocols, and using patient models based on accurate patient anatomy and representing a range of patient sizes. Organ dose estimates were estimated for clinical MDCT exam protocols which pose a specific concern for radiosensitive organs or regions. These dose estimates include estimation of fetal dose for pregnant patients undergoing abdomen pelvis CT exams or undergoing exams to diagnose pulmonary embolism and venous thromboembolism. Breast and lung dose were estimated for patients undergoing coronary CTA imaging, conventional fixed tube current chest CT, and conventional tube current modulated TCM) chest CT exams. The correlation of organ dose with patient size was quantified for pregnant patients undergoing abdomen/pelvis exams and for all breast and lung dose estimates presented. Novel dose reduction techniques were developed that incorporate organ location and are specifically designed to reduce close to radiosensitive organs during CT acquisition. A generalizable model was created for simulating conventional and novel attenuation-based TCM algorithms which can be used in simulations estimating organ dose for any patient model. The generalizable model is a significant contribution of this work as it lays the foundation for the future of simulating TCM using Monte Carlo methods. As a result of this research organ dose can be estimated for individual patients undergoing specific conventional MDCT exams. This research also brings understanding to conventional and novel close reduction techniques in CT and their effect on organ dose.

Real time image guided radiotherapy has been proposed by integrating an in-line 6 MV linear accelerator linac) to a magnetic resonance MR) imager in either a parallel or transverse configuration. In either configuration, magnetic interference in the linac is caused by its immersion in the magnetic fringe fields of the MR imager. Thus in order to minimize the effect of the magnetic interference, investigations on linac performance in external magnetic fields was completed through various simulations. Finite difference and finite element methods as well as particle simulations were performed in order to design an electron gun and an in-line 6 MV linac waveguide. Monte Carlo simulations provided calculations of dose distributions in a water tank from the derived electron phase space at the linac target. The entire simulation was validated against measurements taken from a commercial medical in-line 6 MV linac, other simulation programs, and theory. The validated linac simulation was used to investigate linac performance in external magnetic fields. The results of this investigation showed that the linac had a much lower tolerance to transverse magnetic fields compared to longitudinal fields. While transverse magnetic fields caused a global deflection of the electron beam away from the central axis of the waveguide, longitudinal fields changed the optics of the electron gun in a suboptimal way. Both transverse and longitudinal magnetic fields caused excessive beam loss if the field strength was large enough. Heating caused by excessive beam loss in external magnetic fields was shown to have little effect on the resonant frequency of the waveguide, and any change in dosimetry, if it existed, was shown to be easily corrected using the jaws or multileaf collimators MLCs). It was determined that the low-field parallel configuration linac-MR system investigated did not require any magnetic shielding, so the focus was on shielding the transverse configuration. Using beam loss, MLC motor tolerance to magnetic fields, and MR imager homogeneity as constraints, passive and active magnetic shielding was designed and optimized. Thus through the parallel configuration, or using magnetic shielding, magnetic interference has been reduced to within the linac operational tolerance.

In this thesis, water diffusion in human liver and placenta is studied using diffusion weighted magnetic resonance imaging. For short, randomly oriented vascular segments, intravascular water motion is diffusion-like. For tissues with large vascular compartments the diffusion decay is bi-exponential with one component corresponding to diffusing water and the other to water in the microvasculature. This model, known as the intravoxel incoherent motion IVIM) model, is seldom used with abdominal organs because of motion artifacts. This limitation was overcome for the experiments reported here by introducing: 1) parallel imaging, 2) navigator echo respiratory triggering NRT), 3) a double echo diffusion sequence that inherently compensates for eddy current effects, 4) SPAIR fat suppression and 5) a superior approach to image analysis. In particular, the use of NRT allowed us to use a free breathing protocol instead of the previously required breath hold protocol. The resulting DWI images were of high quality and motion artifact free. Diffusion decays were measured over a larger portion of the decay than had previously been reported and the results are considerably better than those previously reported. For both studies, reliable measurements of the diffusion coefficient D), pseudo-diffusion coefficient D) and perfusion fraction f), were obtained using a region of interest analysis as well as a pixel-by-pixel approach. To within experimental error, all patients had the same values of D 1.10 mum 2/ms ＋/- 0.16 mum2/ms), D* 46 mum2/ms ＋/- 17 mum2/ms) and f 44.0% ＋/- 6.9%) in liver and D 1.8 mum 2/ms ＋/- 0.2 mum2/ms), D* 30 mum 2/ms ＋/- 12 mmu2/ms), and f 40% ＋/- 6%) in the placenta. No dependence on gestational age was found for the placental study. Parametric maps of f and D* were consistent with blood flow patterns in both systems. The model worked well for both investigated organs even though their anatomical structures are quite different. A method for removing rectified noise bias from low intensity magnitude MR images measured with phased array coils is also presented. This algorithm has significance for diffusion decay measurements since it permits the use of low intensity data points which could, for example, allow the acquisition of high resolution parametric maps.

The doses were measured at the depth of 10 cm and at the maximum dose dmax for two energies 6 MV photon and 10 MV photon on Elekta machine. Measuring dose was done by using only two points and comparing the results with percentage depth dose (PDD) for the depth dose curve for both energies. In addition the doses were obtained by using three methods of detectors to measure the dose by using the ion chamber, Thermo luminescence, and films. The results obtained for three measurements agreed within 2% for 6 MV photon and 3% for 10 MV photon by using three different detectors in the clinic. Therefore, these detectors are stable and reliable to be used in clinical applications.

Rapid and sensitive detection of biomolecules is an important issue in nanomedicine. Many disorders are manifested by changes in protein levels of serum and other biofluids. Rapid and effective differentiation between normal and cancerous cells is an important challenge for the diagnosis and treatment of tumor. Likewise, rapid and effective identification of pathogens is a key target in both biomedical and environmental monitoring. Most biological recognition processes occur via specific interactions. Gold nanoparticles (AuNP s) feature sizes commensurate with biomacromolecules, coupled with useful physical and optical properties. A key issue in the use of nanomaterials is controlling the interfacial interactions of these complex systems. Modulation of these physicochemical properties can be readily achieved by engineering nanoparticles surface. Inspired by the idea of mimicking nature, a convenient, precise and rapid method for sensing proteins, cancerous cells and bacteria has been developed by overtaking the superb performance of biological olfactory systems in odor detection, identification, tracking, and location. On the fundamental side, an array-based/’chemical nose’ sensor composed of cationic functionalized AuNPs as receptors and anionic fluorescent conjugated polymers or green fluorescent proteins or enzyme/substrates as transducers that can properly detect and identify proteins, bacteria, and cancerous cells has been successfully fabricated.