Breathing chest radiography using a dynamic flat-panel detector combined with computer analysis

金沢大学大学院医学系研究科保健学専攻Kinetic information is crucial when evaluating certain pulmonary diseases. When a dynamic flat-panel detector (FPD) can be used for a chest examination, kinetic information can be obtained simply and cost-effectively. The purpose of this study was to develop methods for analyzing respiratory kinetics, such as movement of the diaphragm and lung structures, and the respiratory changes in x-ray translucency in local lung fields. Postero- anterior dynamic chest radiographs during respiration were obtained with a modified FPD, which provided dynamic chest radiographs at a rate of 3 frames/s. Image registration for correction of physical motion was followed by measurement of the distance from the lung apex to the diaphragm. Next, we used a cross-correlation technique to measure the vectors of respiratory movement in specific lung areas. Finally, the average pixel value for a given local area was calculated by tracing the same local area in the lung field. This method of analysis was used for six healthy volunteers and one emphysema patient. The results reported here represent the initial stage in the development of a method that may constitute a new method for diagnosing certain pulmonary diseases, such as chronic obstructive pulmonary disease, fibroid lung, and pneumonia. A clinical evaluation of our method is now in progress. (C) 2004 American Association of Physicists in Medicine

Development of a small animal conformal irradiator with dual energy x-ray computed tomography imaging for kilovoltage dosimetry

External beam radiotherapy has become technically sophisticated with image guided radiation therapy (IGRT) and intensity modulated radiation therapy (IMRT). These technologies allow for precise delivery of radiation to geometric targets in cancer patients. However, many questions remain on how to best define targets based on biological information, such as functional imaging, and how to combine radiation with other cancer therapies. To help answer these questions, small animal preclinical studies are needed to generate data to inform clinical trials. However, the precise radiation delivery capabilities of IGRT and IMRT have not been available in the preclinical labs. To enable translational experiments and to address the lack of preclinical radiotherapy technology, a commercial micro-CT was first developed into an image-guided conformal radiotherapy system in this thesis. Computerized asymmetric jaws were constructed, implemented and characterized for the system. A Monte Carlo dose calculation package was successfully configured for the system and verified with film measurements. Respiratory gated imaging and radiotherapy was demonstrated with a phantom and in animals. Secondly, accurate radiation dosimetry reduces uncertainties in preclinical experiments. To achieve accurate dose calculations in the kilovoltage x-ray range where photoelectric effects and Compton scattering dominate, knowledge of material composition and density is needed. Dual energy micro-CT was optimized (including choice of x-ray beam peak voltages, filtrations, and duration) and evaluated for the purpose of characterizing materials. Dual energy CT techniques developed for clinical scanners were adapted and examined for micro-CT. A set of micro-CT phantoms consisting of 11 plastic materials and solutions that spanned a relevant range of compositions was designed and constructed. Initial experiments found beam-hardening image artefacts limited accurate measurements. By switching to a more sensitive detector, x-ray spectra with additional beam filtration were possible and resulted in reduced beam-hardening effects. This improved dual energy micro-CT measurement accuracy of material composition and density. In conclusion, a small animal image-guided conformal radiotherapy system was developed and commissioned for preclinical studies. Dual energy micro-CT was demonstrated as a method to characterize materials to improve kilovoltage dose calculation. This integrated micro-CT based small animal image-guided radiation platform has enabled numerous pre-clinical studies

動画対応フラットパネルディテクタによる肺機能画像診断法 : 肺シンチグラフィ所見との比較

金沢大学医薬保健研究域保健学系Pulmonary ventilation and circulation dynamics are reflected on dynamic chest radiographs as changes in X-ray translucency,i.e., pixel values. The present study was performed to develop a pulmonary functional evaluation method based on the changes in pixel value, and to investigate the clinical usefulness of our method. Sequential chest radiographs of 20 subjects (abnormal,n=12; normal,n=8) during respiration were obtained with a dynamic flat-panel detector (FPD) system. The average pixel value in each local area was measured tracking the same area. To facilitate visual evaluation, the results were mapped on the original image using a grayscale in which small changes were shown in black and large changes were shown in white. In our clinical evaluation in comparison with a pulmonary scintigraphy, pulmonary ventilation disorder was indicated as a reduction of changes in pixel values. In many patients, there was a correlation between our result and a pulmonary scintigraphy (0.7<r, 4 cases; 0.4<r<or=0.7, 6 cases; 0.2<r<or=0.4, 1 case; 0<r<or=0.2, 1 case). The present method with real-time computer analysis is expected to be a rapid and simple method for evaluating pulmonary function and as an additional examination in conventional chest radiography

New Methods for Motion Management During Radiation Therapy

In this thesis, a number of new image-based techniques for the management of intrafractional motion during radiation therapy are presented. Intra-fractional motion describes all kinds of anatomy changes - most prominently respiration - that occur during a single treatment session. Spatially confining the radiation dose to the tumour tissue and thus sparing surrounding healthy tissue is assumed to be crucial for a successful treatment with limited side effects. Unfortunately, the delivery of dose distributions that are sharply confined to the tumour is greatly complicated by patient motion. If not accounted for, this motion will lead to a smearing out of the original dose distribution and will facilitate the redistribution of dose from tumour to healthy tissue. Possible technical solutions for this issue include the interruption of the radiation delivery if the tumour leaves a predefined spatial ‘window’, and the reshaping of the treatment field ‘on-the-fly’ to follow the tumour. Regardless of which delivery techniques is selected, the patient motion needs to be reliably detected in real-time to allow for an adaptation of the treatment delivery. First, we present experimental results for a novel x-ray imaging system that is attached to the treatment delivery device and enables us to continuously monitor the tumour motion during treatment delivery with sub-mm accuracy, a latency better than 90 ms, and a 7 Hz update rate. Second, we present a Monte Carlo simulation for an improved amorphous-silicon flat-panel detector that reduced treatment beam filtration by 60% and long-range MV-scatter by 80%. We conclude this thesis by presenting results of an experimental demonstration of a novel dose-saving actively-triggered 4d cone-beam computed tomography device

Development of a Carbon Nanotube-Based Micro-CT and its Applications in Preclinical Research

Due to the dependence of researchers on mouse models for the study of human disease, diagnostic tools available in the clinic must be modified for use on these much smaller subjects. In addition to high spatial resolution, cardiac and lung imaging of mice presents extreme temporal challenges, and physiological gating methods must be developed in order to image these organs without motion blur. Commercially available micro-CT imaging devices are equipped with conventional thermionic x-ray sources and have a limited temporal response and are not ideal for in vivo small animal studies. Recent development of a field-emission x-ray source with carbon nanotube (CNT) cathode in our lab presented the opportunity to create a micro-CT device well-suited for in vivo lung and cardiac imaging of murine models for human disease. The goal of this thesis work was to present such a device, to develop and refine protocols which allow high resolution in vivo imaging of free-breathing mice, and to demonstrate the use of this new imaging tool for the study many different disease models. In Chapter 1, I provide background information about x-rays, CT imaging, and small animal micro-CT. In Chapter 2, CNT-based x-ray sources are explained, and details of a micro-focus x-ray tube specialized for micro-CT imaging are presented. In Chapter 3, the first and second generation CNT micro-CT devices are characterized, and successful respiratory- and cardiac-gated live animal imaging on normal, wild-type mice is achieved. In Chapter 4, respiratory-gated imaging of mouse disease models is demonstrated, limitations to the method are discussed, and a new contactless respiration sensor is presented which addresses many of these limitations. In Chapter 5, cardiac-gated imaging of disease models is demonstrated, including studies of aortic calcification, left ventricular hypertrophy, and myocardial infarction. In Chapter 6, several methods for image and system improvement are explored, and radiation therapy-related micro-CT imaging is present. Finally, in Chapter 7 I discuss future directions for this research and for the CNT micro-CT.Doctor of Philosoph

3D Imaging for Planning of Minimally Invasive Surgical Procedures

Novel minimally invasive surgeries are used for treating cardiovascular diseases and are performed under 2D fluoroscopic guidance with a C-arm system. 3D multidetector row computed tomography (MDCT) images are routinely used for preprocedural planning and postprocedural follow-up. For preprocedural planning, the ability to integrate the MDCT with fluoroscopic images for intraprocedural guidance is of clinical interest. Registration may be facilitated by rotating the C-arm to acquire 3D C-arm CT images. This dissertation describes the development of optimal scan and contrast parameters for C-arm CT in 6 swine. A 5-s ungated C-arm CT acquisition during rapid ventricular pacing with aortic root injection using minimal contrast (36 mL), producing high attenuation (1226), few artifacts (2.0), and measurements similar to those from MDCT (p\u3e0.05) was determined optimal. 3D MDCT and C-arm CT images were registered to overlay the aortic structures from MDCT onto fluoroscopic images for guidance in placing the prosthesis. This work also describes the development of a methodology to develop power equation (R2\u3e0.998) for estimating dose with C-arm CT based on applied tube voltage. Application in 10 patients yielded 5.48┬▒177 2.02 mGy indicating minimal radiation burden. For postprocedural follow-up, combinations of non-contrast, arterial, venous single energy CT (SECT) scans are used to monitor patients at multiple time intervals resulting in high cumulative radiation dose. Employing a single dual-energy CT (DECT) scan to replace two SECT scans can reduce dose. This work focuses on evaluating the feasibility of DECT imaging in the arterial phase. The replacement of non-contrast and arterial SECT acquisitions with one arterial DECT acquisition in 30 patients allowed generation of virtual non-contrast (VNC) images with 31 dose savings. Aortic luminal attenuation in VNC (32┬▒177 2 HU) was similar to true non-contrast images (35┬▒177 4 HU) indicating presence of unattenuated blood. To improve discrimination between c

Quantitative Optical Studies of Oxidative Stress in Rodent Models of Eye and Lung Injuries

Optical imaging techniques have emerged as essential tools for reliable assessment of organ structure, biochemistry, and metabolic function. The recognition of metabolic markers for disease diagnosis has rekindled significant interest in the development of optical methods to measure the metabolism of the organ. The objective of my research was to employ optical imaging tools and to implement signal and image processing techniques capable of quantifying cellular metabolism for the diagnosis of diseases in human organs such as eyes and lungs. To accomplish this goal, three different tools, cryoimager, fluorescent microscope, and optical coherence tomography system were utilized to study the physiological metabolic markers and early structural changes due to injury in vitro, ex vivo, and at cryogenic temperatures. Cryogenic studies of eye injuries in animal models were performed using a fluorescence cryoimager to monitor two endogenous mitochondrial fluorophores, NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide). The mitochondrial redox ratio (NADH/ FAD), which is correlated with oxidative stress level, is an optical biomarker. The spatial distribution of mitochondrial redox ratio in injured eyes with different durations of the disease was delineated. This spatiotemporal information was helpful to investigate the heterogeneity of the ocular oxidative stress in the eyes during diseases and its association with retinopathy. To study the metabolism of the eye tissue, the retinal layer was targeted, which required high resolution imaging of the eye as well as developing a segmentation algorithm to quantitatively monitor and measure the metabolic redox state of the retina. To achieve a high signal to noise ratio in fluorescence image acquisition, the imaging was performed at cryogenic temperatures, which increased the quantum yield of the intrinsic fluorophores. Microscopy studies of cells were accomplished by using an inverted fluorescence microscope. Fixed slides of the retina tissue as well as exogenous fluorophores in live lung cells were imaged using fluorescent and time-lapse microscopy. Image processing techniques were developed to quantify subtle changes in the morphological parameters of the retinal vasculature network for the early detection of the injury. This implemented image cytometry tool was capable of segmenting vascular cells, and calculating vasculature features including: area, caliber, branch points, fractal dimension, and acellular capillaries, and classifying the healthy and injured retinas. Using time-lapse microscopy, the dynamics of cellular ROS (Reactive Oxygen Species) concentration was quantified and modeled in ROS-mediated lung injuries. A new methodology and an experimental protocol were designed to quantify changes of oxidative stress in different stress conditions and to localize the site of ROS in an uncoupled state of pulmonary artery endothelial cells (PAECs). Ex vivo studies of lung were conducted using a spectral-domain optical coherence tomography (SD-OCT) system and 3D scanned images of the lung were acquired. An image segmentation algorithm was developed to study the dynamics of structural changes in the lung alveoli in real time. Quantifying the structural dynamics provided information to diagnose pulmonary diseases and to evaluate the severity of the lung injury. The implemented software was able to quantify and present the changes in alveoli compliance in lung injury models, including edema. In conclusion, optical instrumentation, combined with signal and image processing techniques, provides quantitative physiological and structural information reflecting disease progression due to oxidative stress. This tool provides a unique capability to identify early points of intervention, which play a vital role in the early detection of eye and lung injuries. The future goal of this research is to translate optical imaging to clinical settings, and to transfer the instruments developed for animal models to the bedside for patient diagnosis