Multispectral fluorescence imaging is a new diagnostic technique with the potential to provide improved detection and classification of atherosclerotic disease. This technique involves imaging the fluorescence response of a tissue region through a tunable band-pass filtering device. The result is a set of images in which each individual image is composed of the fluorescence emission within a specified band of wavelengths. Multispectral imaging combined with angioscopic technology allows direct access to important spectral information and spatial attributes providing the potential for more informed clinical decisions about which, if any, treatment modality is indicated. In this dissertation, the system requirements for an angioscopic system with multispectral imaging capability are identified. This analysis includes a description of the necessary optical components and their characteristics as well as the experimental determination of spectral radiance values for the fluorescence response of human aorta specimens and the estimation of anticipated signal-to-noise ratios for the spectral images. Other issues investigated include the number of spectral images required to provide good classification potential and the best normalization method to be utilized. Finally, the potential utility of the information contained within a multispectral data set is demonstrated. Two methods of utilizing the multispectral data are presented. The first method involves generating a ratio-image from the ratio of the intensities of two spectrally filtered images. The second method consists of using histologically verified training data to train a projector and then applying that projector to a set of spectral images. The result (a weighted sum of the spectral images) provides improved contrast between normal and diseased tissue, and is called an optimized-contrast image. White-light images (generated using an incandescent light source), total-fluorescence images (the fluorescence response without spectral filtering), ratio-images, and optimized contrast images are compared. The results indicate that angioscopic fluorescence imaging appears to be a feasible and potentially useful technique in terms of providing improved detection of atherosclerotic disease. This technique warrants further investigation to further define the system requirements and to evaluate its clinical usefulness including the collection of a more extensive data set and the development of a prototype system.

This dissertation explores a novel design for a surgical probe, a collimatorless coincidence imaging system designed to aid in tumor detection in nuclear medicine. Surgical probes can be maneuvered close to a suspected tumor site, thereby achieving higher resolution and sensitivity than external gamma cameras. However, conventional probes cannot distinguish between distant background variations and small tumors near the probe. Collimatorless coincidence imaging is a new method for suppressing the effects of variations in the background radiation. This decidedly unconventional imaging system images without a collimator or aperture of any kind. The probe design consists of a 10 x 10 array of collimatorless gamma-ray detectors connected by coincidence circuitry. The probe is used with a radionuclide that emits multiple photons per decay, such as ¹¹¹In. The coincidence circuitry triggers data collection only when two photons strike the detectors within a short time interval. Because the photons are emitted independently, the probability of coincident hits on two detectors is proportional to the product of the solid angles subtended by the two detectors. Therefore distant sources have a very low probability of contributing to the data, making them all but invisible to the probe. Data collection from such a system was simulated using a Monte Carlo routine that included absorption, the slight correlation between the directions of the emitted photons, and the presence of accidental coincidences. The data were reconstructed into object representations using the pseudoinverse obtained by singular value decomposition (SVD). The images showed a significant suppression of distant sources when compared to a probe equipped with a conventional parallel-hole collimator. We confirmed in the laboratory, using a point source of In-111 and two CdTe detectors connected by an AND gate, that the falloff in sensitivity was inversely proportional to the fourth power of the distance to the source and that the proportion of true to accidental coincidences followed the predicted relationship to the source activity. We conclude that collimatorless coincidence imaging is promising approach for tumor detection using surgical probes.

Various model observers have been applied to the objective assessment of medical image quality. However, the relevance of this application to clinical efficacy depends largely on how well model observers predict human performance. Attempting to answer this question, this dissertation focuses on the investigation of a linear observer known as the Hotelling observer and a modified version of the Hotelling observer, known as the channelized Hotelling observer. Performances of these observers for a signal-known-exactly detection task are calculated and compared to the performance of the human observer. Several psychophysical studies suggest that the Hotelling observer, formulated on the first- and second-order statistical properties of the images, could predict the human performance very well. To investigate the effect of certain higher-order statistical information on human performance, an experiment was designed in which the mean, variance, and covariance of three groups of images were kept the same, while the shapes of the image grey-level histogram were varied. The results showed little practical difference in the human performance among the three groups; thus the higher-order statistical information represented by the shape of the grey-level histogram did not influence the human observer's signal-detection performance for the task considered in this experiment. Another linear model observer, the nonprewhitening observer has been found in previous work to predict human performance better than the Hotelling observer for images with uniform backgrounds and correlated noise. When the images contain nonuniform background and uncorrelated noise, however, the Hotelling observer is found to be better in predicting human performance. To unify these results, a channelized Hotelling observer was proposed whose performance resembles that of a nonprewhitening observer for images with correlated noise, and that of a Hotelling observer for images with nonuniform background. Moreover, the channelized Hotelling observer is able to predict human performance when images have both the nonuniform background and correlated noise. A nonlinear version of the channelized Hotelling observer has also been found to predict human performance well.

<p>On-board image guidance, such as cone-beam CT (CBCT) and kV/MV 2D imaging, is essential in many radiation therapy procedures, such as intensity modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). These imaging techniques provide predominantly anatomical information for treatment planning and target localization. Recently, studies have shown that treatment planning based on functional and molecular information about the tumor and surrounding tissue could potentially improve the effectiveness of radiation therapy. However, current on-board imaging systems are limited in their functional and molecular imaging capability. Single Photon Emission Computed Tomography (SPECT) is a candidate to achieve on-board functional and molecular imaging. Traditional SPECT systems typically take 20 minutes or more for a scan, which is too long for on-board imaging. A robotic multi-pinhole SPECT system was proposed in this dissertation to provide shorter imaging time by using a robotic arm to maneuver the multi-pinhole SPECT system around the patient in position for radiation therapy. </p><p>A 49-pinhole collimated SPECT detector and its shielding were designed and simulated in this work using the computer-aided design (CAD) software. The trajectories of robotic arm about the patient, treatment table and gantry in the radiation therapy room and several detector assemblies such as parallel holes, single pinhole and 49 pinholes collimated detector were investigated. The rail mounted system was designed to enable a full range of detector positions and orientations to various crucial treatment sites including head and torso, while avoiding collision with linear accelerator (LINAC), patient table and patient.</p><p>An alignment method was developed in this work to calibrate the on-board robotic SPECT to the LINAC coordinate frame and to the coordinate frames of other on-board imaging systems such as CBCT. This alignment method utilizes line sources and one pinhole projection of these line sources. The model consists of multiple alignment parameters which maps line sources in 3-dimensional (3D) space to their 2-dimensional (2D) projections on the SPECT detector. Computer-simulation studies and experimental evaluations were performed as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise and acquisition geometry. In computer-simulation studies, when there was no error in determining angles (&alpha;) and offsets (&rho;) of the measured projections, the six alignment parameters (3 translational and 3 rotational) were estimated perfectly using three line sources. When angles (&alpha;) and offsets (&rho;) were provided by Radon transform, the estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution and detector acquisition geometry. The estimation accuracy was significantly improved by using 4 line sources rather than 3 and also by using thinner line-source projections (obtained by better intrinsic detector resolution). With 5 line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist. </p><p>Simulation studies were performed to investigate the improvement of imaging sensitivity and accuracy of hot sphere localization for breast imaging of patients in prone position. A 3D XCAT phantom was simulated in the prone position with nine hot spheres of 10 mm diameter added in the left breast. A no-treatment-table case and two commercial prone breast boards, 7 and 24 cm thick, were simulated. Different pinhole focal lengths were assessed for root-mean-square-error (RMSE). The pinhole focal lengths resulting in the lowest RMSE values were 12 cm, 18 cm and 21 cm for no table, thin board, and thick board, respectively. In both no table and thin board cases, all 9 hot spheres were easily visualized above background with 4-minute scans utilizing the 49-pinhole SPECT system while seven of nine hot spheres were visible with the thick board. In comparison with parallel-hole system, our 49-pinhole system shows reduction in noise and bias under these simulation cases. These results correspond to smaller radii of rotation for no-table case and thinner prone board. Similarly, localization accuracy with the 49-pinhole system was significantly better than with the parallel-hole system for both the thin and thick prone boards. Median localization errors for the 49-pinhole system with the thin board were less than 3 mm for 5 of 9 hot spheres, and less than 6 mm for the other 4 hot spheres. Median localization errors of 49-pinhole system with the thick board were less than 4 mm for 5 of 9 hot spheres, and less than 8 mm for the other 4 hot spheres. </p><p>Besides prone breast imaging, respiratory-gated region-of-interest (ROI) imaging of lung tumor was also investigated. A simulation study was conducted on the potential of multi-pinhole, region-of-interest (ROI) SPECT to alleviate noise effects associated with respiratory-gated SPECT imaging of the thorax. Two 4D XCAT digital phantoms were constructed, with either a 10 mm or 20 mm diameter tumor added in the right lung. The maximum diaphragm motion was 2 cm (for 10 mm tumor) or 4 cm (for 20 mm tumor) in superior-inferior direction and 1.2 cm in anterior-posterior direction. Projections were simulated with a 4-minute acquisition time (40 seconds per each of 6 gates) using either the ROI SPECT system (49-pinhole) or reference single and dual conventional broad cross-section, parallel-hole collimated SPECT. The SPECT images were reconstructed using OSEM with up to 6 iterations. Images were evaluated as a function of gate by profiles, noise versus bias curves, and a numerical observer performing a forced-choice localization task. Even for the 20 mm tumor, the 49-pinhole imaging ROI was found sufficient to encompass fully usual clinical ranges of diaphragm motion. Averaged over the 6 gates, noise at iteration 6 of 49-pinhole ROI imaging (10.9 µCi/ml) was approximately comparable to noise at iteration 2 of the two dual and single parallel-hole, broad cross-section systems (12.4 µCi/ml and 13.8 µCi/ml, respectively). Corresponding biases were much lower for the 49-pinhole ROI system (3.8 µCi/ml), versus 6.2 µCi/ml and 6.5 µCi/ml for the dual and single parallel-hole systems, respectively. Median localization errors averaged over 6 gates, for the 10 mm and 20 mm tumors respectively, were 1.6 mm and 0.5 mm using the ROI imaging system and 6.6 mm and 2.3 mm using the dual parallel-hole, broad cross-section system. The results demonstrate substantially improved imaging via ROI methods. One important application may be gated imaging of patients in position for radiation therapy.</p><p>A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150-L110 robot). An imaging study was performed with a phantom (PET CT Phantom<super>TM</super>), which includes 5 spheres of 10, 13, 17, 22 and 28 mm in diameter. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single-pinhole collimator both without background in the phantom, and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180 degrees and 228 degrees respectively. The pinhole detector viewed a 14.7 cm-diameter common volume which encompassed the 28 mm and 22 mm spheres. The common volume for parallel-hole was a 20.8-cm-diameter cylinder which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the flat-top table while avoiding collision with the table and maintaining the closest possible proximity to the common volume. For image reconstruction, detector trajectories were described by radius-of-rotation and detector rotation angle &#952;. These reconstruction parameters were obtained from the robot base and tool coordinates. The robotic SPECT system was able to maneuver the parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector to center-of-rotation (COR) distance. In no background case, all five spheres were visible in the reconstructed parallel-hole and pinhole images. In with background case, three spheres of 17, 22 and 28 mm diameter were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameter) were readily observed in the pinhole ROI imaging.</p><p>In conclusion, the proposed on-board robotic SPECT can be aligned to LINAC/CBCT with a single pinhole projection of the line-source phantom. Alignment parameters can be estimated using one pinhole projection of line sources. This alignment method may be important for multi-pinhole SPECT, where relative pinhole alignment may vary during rotation. For single pinhole and multi-pinhole SPECT imaging onboard radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC. In simulation studies of prone breast imaging and respiratory-gated lung imaging, the 49-pinhole detector showed better tumor contrast recovery and localization in a 4-minute scan compared to parallel-hole detector. On-board SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.</p> / Dissertation

M.Med. (Diagnostic Radiology), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Pneumocystis jirovecci pneumonia (PJP) in HIV/AIDS is a significant opportunistic infection. As CD4 counts decrease, so does specificity of chest X-ray (CXR). AIM: To determine the proportion of bronchoscopically proven PJP in HIV infected adults, CD4 counts, CXR signs and compare PJP to TB. METHODS: The proportion of bronchoscopically proven PJP and co-infection was determined. Sensitivity and specificity of CXR for the diagnosis of PJP and TB, and frequency of CXR signs were determined. RESULTS: PJP was present in 26.6% and co-infection 19%. Median CD4 (13 cell/mm3) was significantly lower for PJP patients (p = 0.0089). CXR sensitivity for PJP was 33% and specificity was 100%. Bilateral, multilobar and diffuse disease, bronchopneumonia, nodules and cavitation overlapped for PJP and TB. Unilateral and unilobar disease indicated TB over PJP. Effusions and lymphadenpopathy were not seen with PJP. CONCLUSION: PJP makes up a quarter of indeterminate diagnoses in HIV infected adults. Sensitivity of diagnosis on CXR is low. The CXR diagnosis of TB is made more confidently, but is overcalled. In patients with low CD4 levels, a diagnosis of PJP should be considered as important as TB.

BACKGROUND: Lehurutshe Hospital is a district hospital situated in rural North West Province of South Africa. The Hospital offers basic radiological services such as X-rays of the chest, abdomen, extremities and skull according to the norms and standards set by the National Department of Health for a level one hospital. According to 2008/2009 data from the Hospital, it is evident that the number of patients requiring radiology services is increasing. However, no systematic study has been done to determine the reasons and effects of this increasing caseload on the Radiology Unit of the Hospital. This study seeks to establish the caseload and the resources utilised for the services rendered by the Radiology Unit in Lehurutshe Hospital with specific focus on the patient profile and material and human resources utilisation. AIM: To assess the utilization of the Radiology Unit at Lehurutshe Hospital in terms of caseload, profile of patients, and resource utilization from 01 January to 31 December 2009 METHODOLOGY: This was a cross sectional study. The setting was the Radiology Unit of the Lehurutshe Hospital in Zeerust town, Ngaka Modiri Molema District in the North West Province. A retrospective record review was done and information was extracted from the Hospital information system on various variables that are relevant to the functions and resource utilization of the Radiology Unit, including caseload, profile of patients, resource utilization and workload of staff. No primary data was collected. RESULTS: The study found that more than 5000 patients were seen and radiological examinations were done during this period with a total number of public patients being significantly higher than private patients. Nearly 500 radiological examinations were done per month. The wide variation in the number of examinations done per month was probably due to seasonality, which may affect operational planning and inventory management at the Unit. Almost 50% of the radiological examinations were chest X-rays. Other examinations include X-ray of the upper and lower extremities and ultrasound examination for obstetrics and gynaecology. These examinations were done based on various clinical indications. A significant number of public patients seen at the Unit were infants, children and teenagers. The private patients were from an older age group. The majority of patient were unemployed and indigent. The material resources used in the Unit includes X-ray films, chemicals (developers and fixers) and ultrasound gel. The Unit has two radiographer and one radiographer assistant. In addition, a medical doctor read the X-rays as and when necessary. The direct costs incurred at the unit include use of material resources, maintenance of equipments (service contract) and compensation of employees. Total direct cost during the study period was R 650 803.89, most of which were incurred due to compensation of employees and maintenance of radiological equipments. Patient to staff ratio at the unit was quiet low and it shows there is spare capacity at the Unit, which could easily be used for income generation by the provision of services to private patients. CONCLUSION: This is probably the first study conducted at a radiology unit of a district hospital in South Africa. This study documented important information, which was not published before.

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.

Intensity Modulated Radiation Therapy (IMRT) is a complex form of radiation delivery for the treatment of malignant tumours and other diseases. In IMRT treatment planning, quantitative assessment is crucial to measure and improve the plan quality and treatment delivery. The search for simple and universal quantitative metrics to assess IMRT treatment plan quality has been identified as important but as yet not entirely successful. The aim of this thesis was to assess the IMRT treatment plan quality by establishing quantitative metrics for planning conformity and complexity. The metrics proposed in this work were simple, reproducible and universally applicable to all IMRT techniques, which included step-and-shoot IMRT (SSIMRT), volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT). Two metrics, conformity index (CI) and conformation number (CN) were adopted to quantify the plan conformity. The data used for CI and CN calculations were easily retrieved from dose volume histogram (DVH). By reporting both of these metrics, comprehensive information on target coverage and irradiation of normal tissues could be provided. For the quantification of planning complexity, a new and novel spatial complexity matrix (SCM) was introduced to measure the average dose gradient of a dose profile. In addition, the spatial frequency ratio (SFR) was established to explore the proportion of rapidly varying dose with distance in a treatment plan by using one-dimensional power spectral density (1D PSD). Virtual phantoms were developed for the initial quantitative assessment, in order to form a basis for treatment plan inter-comparisons amongst the different IMRT techniques. A series of multi organs at risk (OARs) phantoms was developed to simulate the planning target volume (PTV) and OARs for different configurations. A virtual prostate phantom was also designed to include a unique shape of PTV and the OAR in close proximity to PTV, in order to mimic clinical prostate case. Quantitative assessments were undertaken on all the IMRT plans generated using the virtual phantoms. The results of these phantom studies have shown for the first time, the feasibility of the developed quantitative metrics for assessing plan quality. Following the successful application of SCM and SFR on the phantom plans, verification work was undertaken to demonstrate the clinical relevance of these self-developed complexity metrics. A retrospective study was carried out to assess the complexity of plans for the treatment of prostate and head and neck tumours. The information contained in DICOM-RT objects were utilised to acquire dose data from the corresponding dose plane. A qualitative survey on plan complexity was also conducted amongst treatment planners, to demonstrate the correlation between the qualitative and quantitative results. These preliminary studies demonstrated the successful application of the self-developed complexity metrics on clinical IMRT treatment plans. In conclusion, the work in this thesis has demonstrated the successful establishment of quantitative metrics for assessing plan conformity and complexity of different IMRT techniques. These metrics were considered as universal tools for the inter-comparison of plan quality for different IMRT techniques and were successfully applied and translated from phantom studies to the clinical setting. Whilst the judgment and experience of the treatment planner undoubtedly remains paramount for making a final decision on the best plan in the interest of the patient, it is expected that the use of quantitative metrics will provide an effective means of benchmarking performance, minimising treatment plan variability and enhancing the quality of IMRT treatment planning.