This investigation represents an attempt to evaluate the damaging effects of hyperthermia on mammalian cells, specifically Bp-8 murine sarcoma cells. Two types of heat damage were studied, thermal radiosensitization and direct thermal cell death. The experiments were designed to answer two fundamental questions: (1) Do thermal radiosensitization and direct thermal death share a common lesion? (2) What are the factors responsible for the enhanced thermal sensitivity of tumors as compared to normal body cells? / (I) Three types of experiments provided evidence against a common mode of action for thermal radiosensitization and direct thermal death. (1) Evaluation of kinetics of heat and radiation death. (2) Thermal radiosensitization and direct heat death as a function of heating time. (3) Independent modification of radiosensitization and thermal death. / (II) Although the two types of heat damage do not share the same mode of action, the two effects show certain common features and one is the fact that tumors are more sensitive to heat than normal body cells. This enhanced thermal sensitivity of tumors may be due to (a) poorly oxygenated regions (hypoxia) in tumors which unable them to deal with the adverse consequences of hyperthemia. (b) hypoxia may enhance tumor glycolysis, in turn cause tumor acidification and reduce the resistance of acidified cells. / To evaluate the influence of these factors on thermal response of cells, a method was developed to permit independent variation of cell pH and environmental oxygen. Experiments on the effects of cellular acidification indicated that reduced intracellular pH and not reduced environmental pH causes pronounced enhancement of thermal damage. Studies on the effect of acute hypoxia on thermal sensitization indicated that thermal radiosensitization and direct thermal death is the same for both euoxic and hypoxic cells. / In conclusion, it appears that hypoxia indued tumor acidification rather than hypoxia per se is responsible for the enhanced thermal sensitization of tumors. Moreover, the degree of thermal sensitization is proportional to the degree of intracellular and not environmental acidification. / Source: Dissertation Abstracts International, Volume: 42-06, Section: B, page: 2256. / Thesis (Ph.D.)--The Florida State University, 1981.

Synchronized suspension cultures of Chinese hamster ovary (CHO) cells were labeled with ('125)I-iododeoxyuridine (('125)IUdR) in the presence and absence of drugs to permit the selective incorporation of ('125)IUdR into different subfractions of DNA. Control experiments with cells subjected to random labeling with ('125)IUdR yielded a dose-survival curve with a D(,o) of 96 decays/cell. To evaluate the possibility that damage to mitochondrial DNA might contribute to the lethal effects of radiation, the ('125)I response was examined for cells labeled in the presence of berenil, a drug which selectivity inhibits mitochondrial DNA replication. Inhibition of ('125)I incorporation into mitochondrial DNA did not change the overall radiation response of CHO cells. It can be concluded, therefore, that damage to mitochondrial DNA does not contribute to radiation-induced cell lethality, and the primary target for radiation death must be located in the cell nucleus. / To test the hypothesis that the nuclear genome represents a homogeneous target for radiation damage, the ('125)I response of randomly labeled cells was compared to that of cells where only a minute subfraction of the nuclear DNA was labeled. Non-random labeling of a subfraction of DNA was achieved by pairing ('125)IUdR with aphidicolin, a drug which appears to restrict DNA replication to the small portion of the DNA which is closely associated with the replication complex at the nuclear matrix. ('125)I decays in this subfraction of DNA proved to be considerably more toxic (D(,0): 30 decays/cell) to CHO cells then randomly distributed ('125)I decays (D(,0): 96 decays/cell). / These findings suggest that the cellular genome is not a uniform target for radiation damage. The presence or absence of mitochondrial DNA damage does not influence the extent of radiation-induced cell death. Even within the nuclear genome, ('125)I decays in different subfractions of DNA result in radically different biological effects. It must be concluded, therefore, that the cellular genome is subdivided into target loci which are inhomogeneous with respect to radiation sensitivity. / Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1696. / Thesis (Ph.D.)--The Florida State University, 1984.

Source: Dissertation Abstracts International, Volume: 40-06, Section: B, page: 2555. / Thesis (Ph.D.)--The Florida State University, 1979.

Source: Dissertation Abstracts International, Volume: 38-04, Section: B, page: 1598. / Thesis (Ph.D.)--The Florida State University, 1976.

Source: Dissertation Abstracts International, Volume: 39-06, Section: B, page: 2691. / Thesis (Ph.D.)--The Florida State University, 1978.

CHO cells were pulse-labeled with $\rm\sp{125}I$-iododeoxyuridine during early-S phase, harvested 30 min or 5 h after labeling for accumulation of $\rm\sp{125}I$ decays. Cells harvested 30 min after labeling yielded low-LET survival curves (large shoulder, $\rm D\sb0$ 136 decays/cell); cells harvested at hour 5 showed a high-LET pattern of cell killing (no shoulder, $\rm D\sb0$ 45 decays/cell). Surprisingly, the low-LET to high-LET shift in $\rm\sp{125}I$ action was abolished in cells previously exposed to HAT medium; both 30 min and 5 h groups exhibited high-LET-type cell killing (no shoulder, $\rm D\sb0$ 52 decays/cell). The striking difference in cell death was not accompanied by any change in the induction or repair of DNA DSBs as measured by neutral filter elution. These findings suggest that cell killing may not be directly linked to DNA DSBs, and support our earlier conclusion that damage to higher-order genome structures may be important in radiation-induced cell death. / In related experiments, synchronized CHO cells were pulse-labeled with $\rm\sp{125}IUdR$ in S phase and harvested for decay accumulation at the $\rm G\sb2$ phases of two successive cell cycles. When decays were accumulated during the first $\rm G\sb2$ phase after labeling, cell survival followed a high-LET-type pattern characteristic of single-hit kinetics of cell killing (N = 1, $\rm D\sb0$ 40 decays/cell). In contrast, decays during the second $\rm G\sb2$ phase induced cell death with dual-hit kinetics (N = 2, $\rm D\sb0$ 80 decays/cell). A similar divergence in $\rm\sp{125}I$ action was also observed for micronucleus formation and HGPRT mutations. In short, $\rm\sp{125}I$-induced cellular damage can vary depending on whether the decays occur in daughter (first $\rm G\sb2)$ or parental (second $\rm G\sb2)$ DNA. These results imply that parental and daughter DNA strands show different spatial organization in the mammalian genome. / Source: Dissertation Abstracts International, Volume: 56-07, Section: B, page: 3633. / Major Professor: Kurt G. Holer. / Thesis (Ph.D.)--The Florida State University, 1995.

<p>X-ray mammography is the most widely used breast cancer imaging technique. However, over 400,000 women newly diagnosed each year are misdiagnosed and undergo a biopsy. Current mammography techniques are limited by: (1) low image contrast, especially in women with dense breasts; (2) difficulty in diagnosing and detecting lesions close to the chest wall and in women with radiographically dense breasts; (3) structural overlap onto a two-dimensional (2D) image plane; and (4) patient discomfort due to breast compression. Therefore, three-dimensional (3D) tomographic breast imaging approaches for pendant, uncompressed breasts have been explored to overcome these limitations and improve the detection of breast lesions. The goal of this thesis is to characterize and implement a dual-modality SPECT-CT dedicated breast imaging system that can overcome these limitations and integrate both metabolic and anatomical information to further improve the visual quality and quantitative accuracy over independent systems alone.</p><p>Initial work on this thesis started out with characterizing the modulation transfer function (MTF) in 3D for the independent dedicated SPECT and CT systems. Using a novel phantom to measure the MTF at different locations in a 3D reconstructed volume, results show that acquiring images with a step-and-shoot mode and with trajectories that meet the sampling criteria, uniform resolution throughout a 3D reconstructed volume is obtained. </p><p>The effects of sampling and system geometry on the reconstructed CT images are investigated. As expected, constraining the x-ray source and detector to a circular tilt yields insufficiently sampled reconstructed images, which contain geometric distortions, reconstruction inaccuracies, and cupping artifacts. Although beam hardening and scatter are considered to be the main causes of cupping artifacts in the reconstructed CT images, this study suggests that insufficient sampling might be a third cause to cupping artifacts in the reconstructed images. An additional finding in this study is that despite the insufficient sampling in the reconstructed CT images, high frequency objects (small size) are preserved more than low frequency objects (large size). </p><p>Using a lateral offset geometry (i.e. the entire system shifted such that the central ray of the cone-beam is at an offset with respect to the COR) in CT has also been shown previously to introduce circular and cylindrical artifacts in the reconstructed coronal and sagittal CT slices, respectively. Monte Carlo studies show that these artifacts are due to mechanical detector misalignment. However, cropping the projections, such that there is less of an overlap between conjugate projections, or placing the system in a centered geometry can eliminate these artifacts.</p><p>Next, the dual-modality SPECT-CT scanner is designed and built. The performance of this scanner is evaluated with geometric and anthropomorphic phantoms. Despite only nearly complete sampling from both systems, results illustrate that SPECT and CT images can be registered and fused with minimal error.</p><p>The feasibility of using the reconstructed CT images to quantify different tissue components is also investigated by using different materials (acrylic, delrin, polyethylene, and fat-equivalent and glandular-equivalent plastics) and a cadaver human breast. By implementing scatter correction using the beam stop approach, scatter corrected reconstructed images yield attenuation coefficient values to within 11% of their actual values.</p><p>Finally, few clinical studies are done to evaluate the effectiveness of the dual-modality scanner. Although the CT is currently limited in the amount of breast volume that can be imaged, reconstructed images appear to have minimal distortion and reconstruction inaccuracy. Fused SPECT-CT images also show the significance of using functional information from SPECT to help localize the lesion in the anatomical CT images. </p><p>The dual-modality SPECT-CT scanner has successfully demonstrated its capability to uniformly sample an uncompressed breast with 3D complex trajectories that meet the sampling criteria and provide tissue quantification and localization information. This system will be a clinically useful imaging tool in detecting cancer, especially in women with high risk of breast cancer, monitoring treatment therapies, and improving surgical biopsy guidance.</p> / Dissertation

A novel Fourier technique for solving a wide variety of boundary value problems is introduced. The technique, called Fourier projection, is based on the geometric properties of vector calculus operators in reciprocal space. Fourier projection decomposes arbitrary vector fields into collections of irrotational and/or divergenceless dipole subfields. For well-posed problems, Fourier projection algorithms can calculate unknown field values from a knowledge of primary sources and boundary conditions. Specifically, this technique is applied to several problems associated with biomagnetic imaging, including volume current calculations and equivalent surface current solutions. In addition, a low-cost magnetic field mapping system designed to aid reconstruction algorithm development is described.

This dissertation explores the application of objective assessment of image quality (OAIQ) to hardware evaluation for both linear shift-variant and nonlinear imaging systems. We define our task to be the detection of a known signal in either a uniform or structured background. In particular, we study the detection of signals in digital radiography and optical tomography. In digital radiography, current figures of merit are based on stationarity assumptions on the data. The Hotelling observer as we compute it does not make such assumptions. We quantify, from a detection-theoretic perspective, the errors incurred by using stationarity assumptions for nonstationary digital data. We find that by using Monte Carlo methods, the Hotelling observer carries over to the nonlinear setting, and we use it to study spatially varying detectability in optical tomography. In optical tomography there are several data types that can be used to detect signals. Using our methodology, we quantify the information content of those data types. Our results show that information content depends on the type of signal and background as well as how deep the signal is in the tissue. This type of analysis is meant to guide experimental techniques to be suited for the desired detection task.

In this dissertation we explore theoretical and computational methods to investigate Bayesian ideal observers for performing signal-detection tasks. Object models are used to take into account object variability in image backgrounds and signals for the detection tasks. In particular, lumpy backgrounds (LBs) and Gaussian signals are used for various paradigms of signal-detection tasks. Simplified pinhole imaging systems in nuclear medicine are simulated for this work. Markov-chain Monte Carlo (MCMC) methods that estimate the ideal observer test statistic, the likelihood ratio, for signal-known-exactly (SKE) tasks, where signals are nonrandom, are employed. MCMC methods are extended to signal-known-statistically (SKS) tasks, where signals are random. Psychophysical studies for the SKE and SKS tasks using non-Gaussian and Gaussian distributed LBs are conducted. The performance of the Bayesian ideal observer, the human observer, and the channelized-Hotelling observer for the SKE and SKS tasks is compared. Human efficiencies for both the SKE tasks and SKS tasks are estimated. Also human efficiencies for non-Gaussian and Gaussian-distributed LBs are compared for the SKE tasks. Finally, the theory of the channelized-ideal observer (CIO) is introduced to approximate the performance of the ideal observer by the performance of the CIO in cases where the channel outputs of backgrounds and signals are non-Gaussian distributed. Computational approaches to estimate the CIO are investigated.