Current biophysical studies of membrane proteins are centered on the relation of their structures to key biological functions of membranes in terms of lipid-protein interactions. The conformational transition of rhodopsin from Metarhodopsin I to Metarhodopsin II (Meta I-Meta II) is the triggering event for the visual process. Meta II is the activated form of the visual receptor and binds a signal transducing G protein (transducin), followed by two amplification stages which lead to generation of a visual nerve impulse. Herein, flash photolysis and surface plasmon resonance (SPR) spectroscopy techniques have been used to monitor the Meta I-Meta II transition of rhodopsin in various membrane recombinants. The flash photolysis experiments clearly show a substantial shift to the left of the Meta I-Meta II equilibrium for rhodopsin in egg phosphatidylcholine recombinant membranes. Investigation of the influences on rhodopsin function by non-lamellar forming lipids reveals a characteristic relationship between the Gibbs free energy change for the Meta I-Meta II equilibrium of rhodopsin and the intrinsic curvature of the lipid bilayer. Complementary SPR studies suggest a protrusion of the protein at the activated Meta II state which may be associated with exposure of recognition sites for the signal transducing G protein on the cytoplasmic surface of rhodopsin. All the experimental results obtained here are consistent with the hypothesis of a new flexible surface biomembrane model. The Meta II state is favored by a negative spontaneous curvature of the bilayer, corresponding to an imbalance of the lateral forces within the polar head groups and acyl chains. The mean curvature of membrane bilayer in the Meta II state reflects the small spontaneous curvature of the lipid bilayer in the vicinity of protein. Relief of the lipid curvature frustration in the Meta II state energetically couples the lipids to the photoexcitation of rhodopsin. Consideration of the various energetic contributions suggests the bilayer curvature free energy provides a reservoir of work in the modulation of rhodopsin function in the visual process. These studies that biophysical properties of the liquid-crystalline lipid bilayer are important in relation to protein function and may be relevant to the biomedical investigations of visual dysfunction.

A practical, field-capable, 3.0 to 5.0 μm mid-wave infrared Computed-Tomography Imaging Spectrometer (CTIS) has been demonstrated. The CTIS employs a simple optical system in order to measure the object cube without any scanning . The data is not measured directly, but in a manner which requires complicated post-processing to extract an estimate of the object's spectral radiance. The advantage of a snapshot imaging spectrometer is that it can collect information about a dynamic event which a standard scanning spectrometer could either miss or corrupt with temporal artifacts. Results were presented for reconstructions of laboratory targets with sampling up to 46 x 46 x 21 voxels over a variable field-of-view, or 0.1 μm spectral sampling. Demonstration of the snapshot capability has been performed on both static targets and targets with rapidly varying content. The contents of this dissertation are directed towards two ends. The primary undertaking is a realization of the theoretical model of the CTIS is a practical, field-capable MWIR instrument. The design, calibration, and operation of the MWIR CTIS are explained in detail in the text and appendices. Of additional interest is the advancement of the theory to improve the design and functionality of the spectrometer. A new algorithm for design of the holographic disperser component of the CTIS is introduced. The design process dramatically extends the set of possibilities for the disperser. In order to improve the reconstruction potential of the spectrometer, the analytic expressions which describe the CTIS have been expanded into a principal component basis set. The result is a technique for creating an initial estimate of the object and a technique for improving the reconstruction algorithm.

Glaucoma is a set of diseases that cause optic nerve damage and visual field loss. The most important risk factor for the development of glaucoma is elevated intraocular pressure. One approach used to alleviate the pressure increase is to surgically install glaucoma implants. Optical coherence tomography (OCT) is an imaging modality capable of acquiring cross-sectional images of tissue using back-reflected light. The images have a resolution of 10-15μm, and are thus best suited for visualizing tissue layers and structures. OCT images of some tissue types have few or no features in this size range but display a characteristic repetitive structure due to speckle. The purpose of this research was to show that OCT is capable of visualizing tissue changes, such as those associated with a healing response to glaucoma implants. A new OCT handheld probe was developed to facilitate in vivo imaging in rabbit eye studies. The OCT probe consisted of a mechanical scaffold designed to allow the imaging fiber to be held in a fixed position with respect to the rabbit eye, with minimal anesthesia. A piezo-electric lateral scanning device allowed the imaging fiber to be scanned across the tissue so that 2-D images may be acquired. Preliminary analysis of OCT images of two types of glaucoma implants indicates that OCT can visualize the development of fibrous encapsulation of the implant, tissue erosion and tube position in the anterior chamber. The application of statistical and spectral texture analysis techniques was investigated for differentiating tissue types based on the structural and speckle content in OCT images. Excellent correct classification rates were obtained for images of tissues and tissue phantoms that had slight visual differences and reasonable rates were obtained with nearly identical-appearing images of tissues and tissue phantoms. This study shows that OCT is capable of visualizing structural changes, associated with the healing response, on the order of tens to hundreds of microns. OCT also shows promise in being able to detect sub-resolution tissue healing response changes, by quantifying the changes in the speckle seen in OCT images, using texture analysis.

Current electron beam treatment planning algorithms are inadequate to calculate dose distributions in heterogeneous phantoms. Fast Monte Carlo algorithms are accurate in general but their clinical implementation needs validation. Calculations of electron beam dose distributions performed using the fast Monte Carlo system XVMC and the well-benchmarked general-purpose Monte Carlo code EGSnrc were compared with measurements. Irradiations were performed using the 9 MeV and 15 MeV beams from the Clinac 18 accelerator with standard conditions. Percent depth doses and lateral profiles were measured with thermoluminescent dosimeter and electron diode respectively. The accelerator was modelled using EGS4/BEAM, and using an experiment-based beam model. All measurements were corrected by EGSnrc calculated stopping power ratios. Overall, the agreement between measurement and calculation is excellent. Small remaining discrepancies can be attributed to the non-equivalence between physical and simulated lung material, precision in energy tuning, beam model parameters optimisation and detector fluence perturbation effects.

Abnormal heart rhythms are often associated with serious illness and sometimes cause death. A new strategy to control cardiac arrhythmias involves precisely-timed electrical stimulation of the heart in an attempt to restore normal dynamics. In the first part of this thesis, I demonstrate that a particular abnormal heart rhythm is caused by a period-doubling bifurcation. I describe a new control technique that suppresses the abnormal rhythm by directing the timing of electrical stimuli according to a simple feedback algorithm. Subsequent analysis of the feedback controller revealed a rich structure of stability zones that can be used for automatic adaptation of the previously fixed feedback gain parameter. / While electrical stimulation of the heart guided by feedback control is a promising new treatment, the standard means of controlling an abnormal heart rhythm involves accurate diagnosis of the arrhythmia mechanism followed by appropriate medical or surgical intervention. Since different arrhythmia mechanism often have very different treatments, accurate diagnosis is crucial. In the second part of this thesis, I describe a new diagnostic technique that identifies the different spatio-temporal symmetry properties of electrical wave patterns underlying different mechanisms of cardiac arrhythmia. For one of the arrhythmia mechanisms, the surgical treatment involves locating and destroying an abnormal region of the heart that generates unwanted electrical oscillations. I present new techniques for locating these abnormal regions and I suggest a procedure to confirm when the correct location has been found.

In positron emission mammography, the use of planar detector limits the angular coverage and introduces more noise than conventional positron emission tomography. / We first studied the sampling artifacts introduced from the use of discrete crystals. The images are reconstructed by back-projecting lines of response from and to the centroid of interaction within the crystal. We postulate that the sampling artifact should be reduced by allowing the lines of response to shift away from the centroid towards the next most probable crystal element. / We then studied noise in the peripheral region of the images. The solid angle function is an image uniformity correction function. The solid angle function is the last thing applied before the images are displayed. We postulate that image quality should improve by re-ordering the solid angle function and the smoothing algorithm. / These two techniques have shown an improvement in contrast, resolution, and noise. An ROC curve analysis showed an improvement of 9.5 % in accuracy.

The goal of Total Skin Electron Therapy (TSET) is to deliver a uniform dose to the patient's entire skin to a limited depth while sparing the body organs. Due to the laborious commissioning process, it is helpful to use the Monte Carlo (MC) method for the procedure and treatment planning. Calculations of dosimetric quantities were performed with EGSnrc/BEAM MC codes as well as with the fast MC code XVMC. The linac model for a 6 MeV Varian CL21EX accelerator was established by measuring the electron focal spot size with a slit camera. Using this measured focal spot value in our proposed divergent beam model, an improved result for large field profiles can be achieved. Measured PDDs and profiles under standard set-up and TSET conditions were compared to MC calculations. Overall, satisfactory results were obtained except for simulations with an additional scattering filter, suggesting the composition, density and dimensions of the filter need to be confirmed.

The goal of conformal radiation techniques is to improve local tumor control through dose escalation to target volumes while at the same time sparing surrounding healthy tissue. Accurate target volume delineation is essential in achieving this goal to avoid inadequate tumor coverage and/or irradiation of an unnecessary volume of healthy tissue. Respiratory motion is known to be the largest intra-fractional organ motion and the most significant source of uncertainty in treatment planning for chest lesions. A method to minimize effects of respiratory motion is to use four-dimensional (4D) radiotherapy. / A novel scanning procedure for 4D CT data acquisition is described in this work. Three single-slice helical scans are acquired simultaneously with the real-time tracking of several markers placed on a moving phantom. At the end of the three scans. CT data is binned into different respiratory phases according to the externally recorded respiratory signal and the scanned volume is reconstructed for several respiratory phases. The 4D CT images obtained show an overall improvement when compared to conventional CT images of a moving phantom.

A variety of amphiphilic helical peptides have been shown to exhibit a transition from adsorbing parallel to a membrane surface at low concentrations to inserting perpendicularly into the membrane at high concentrations. This transition has been correlated to the peptides' cytolytic activities. Alamethicin, a 20 amino acid peptide, is an example of an amphiphilic helical peptide. Previous studies of alamethicin in diphytanoyl phosphatidylcoline (DPhPC) lipid bilayers showed that alamethicin were adsorbed in the lipid polar region at low concentrations. X-ray diffraction experiments showed that the bilayer thickness of DPhPC decreased with increasing alamethicin concentration in proportion to the peptide lipid molar ratio from 1/150 to 1/47 (Wu et al., 1995); the latter is near the threshold of the critical concentration for insertion, 1/40. This thesis will focus on the high concentration states of alamethicin in lipid bilayers. A new technique of x-ray and neutron in-plane scattering is described. With neutron in-plane scattering, the aqueous pores ($\ge20$A in diameter) formed by inserted alamethicin in lipid bilayers were directly observed. DPhPC with alamethicin at concentrations above the critical concentration for insertion was studied by x-ray lamellar diffraction. The bilayer thickness of DPhPC first decreases as the peptide begins to insert and then increases after a substantial fraction of the peptide is inserted. Huang (1995) speculated that the peptide insertion transition was caused by the membrane deformation energy. This idea is extended to the high concentration region and is used to explain qualitatively the mechanics of the peptide insertion transition.

Kubo's generalized cumulant expansion theorem is used to derive a theoretical expression for the nuclear magnetic resonance (NMR) signal received from a fluid moving in a time-dependent magnetic field gradient. Described in general terms by time-dependent correlation functions, this expression is used to investigate a new statistical model of microcirculation that incorporates both coherent and incoherent flow effects at the microscopic level. Based on a simple picture of the intravoxel environment, this model is developed by considering an arbitrary distribution of tortuous capillary flows. A statistical analysis of the Langevin equation describing slow tortuous capillary flow as a stochastic process reveals precisely how both coherent and incoherent flow effects contribute to the overall attenuation of the NMR spin-echo. Velocity compensated and non-compensated diffusion matched spin-echo imaging sequences are utilized to separate and quantify these respective effects noninvasively on phantoms of stationary and flowing fluid.