Showing papers by "David W. Holdsworth published in 2007"

A quality assurance phantom for the performance evaluation of volumetric micro-CT systems

Abstract: Small-animal imaging has recently become an area of increased interest because more human diseases can be modeled in transgenic and knockout rodents. As a result, micro-computed tomography (micro-CT) systems are becoming more common in research laboratories, due to their ability to achieve spatial resolution as high as 10 microm, giving highly detailed anatomical information. Most recently, a volumetric cone-beam micro-CT system using a flat-panel detector (eXplore Ultra, GE Healthcare, London, ON) has been developed that combines the high resolution of micro-CT and the fast scanning speed of clinical CT, so that dynamic perfusion imaging can be performed in mice and rats, providing functional physiological information in addition to anatomical information. This and other commercially available micro-CT systems all promise to deliver precise and accurate high-resolution measurements in small animals. However, no comprehensive quality assurance phantom has been developed to evaluate the performance of these micro-CT systems on a routine basis. We have designed and fabricated a single comprehensive device for the purpose of performance evaluation of micro-CT systems. This quality assurance phantom was applied to assess multiple image-quality parameters of a current flat-panel cone-beam micro-CT system accurately and quantitatively, in terms of spatial resolution, geometric accuracy, CT number accuracy, linearity, noise and image uniformity. Our investigations show that 3D images can be obtained with a limiting spatial resolution of 2.5 mm(-1) and noise of +/-35 HU, using an acquisition interval of 8 s at an entrance dose of 6.4 cGy.

Fast retrospectively gated quantitative four-dimensional (4D) cardiac micro computed tomography imaging of free-breathing mice.

Abstract: OBJECTIVE We sought to demonstrate retrospectively gated dynamic 3D cardiac micro computed tomography (CT) of free-breathing mice. MATERIALS AND METHODS Five C57Bl6 mice were scanned using a cone-beam scanner with a slip-ring-mounted flat-panel detector. After the injection of an intravascular iodinated contrast agent, projection images were acquired over the course of 50 seconds, while the scanner rotated through 10 complete rotations. The mouse respiratory and electrocardiogram signals were recorder simultaneously with image acquisition. After acquisition, the projection images were retrospectively sorted into projections belonging to different cardiac time points, occurring only during expiration. RESULTS Dynamic 3D cardiac images, with isotropic 150-microm voxel spacing, were reconstructed at 12-millisecond intervals throughout the cardiac cycle in all mice. The average ejection fraction and cardiac output were 58.2+/-4.6% and 11.4+/-1.3 mL/min, respectively. The measured entrance dose for the entire scan was 28 cGy. Repeat scans of the same animals showed that intrasubject variability was smaller than intersubject variability. CONCLUSIONS We have developed a high-resolution micro computed tomography method for evaluating the cardiac function and morphology of free-breathing mice in acquisition times shorter than 1 minute.

Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound

Abstract: We report the first application of high-frequency three-dimensional power Doppler ultrasound imaging in a genetically engineered mouse (GEM) prostate cancer model. We show that the technology sensitively and specifically depicts functional neoangiogenic blood flow because little or no flow is measurable in normal prostate tissue or tumors smaller than 2-3 mm diameter, the neoangiogenesis "switch-on" size. Vascular structures depicted by power Doppler were verified using Microfil-enhanced micro-computed tomography (micro-CT) and by correlation with microvessel distributions measured by immunohistochemistry and enhanced vascularity visualized by confocal microscopy in two GEM models [transgenic adenocarcinoma of the mouse prostate (TRAMP) and PSP94 gene-directed transgenic mouse adenocarcinoma of the prostate (PSP-TGMAP)]. Four distinct phases of neoangiogenesis in cancer development were observed, specifically, (a) an early latent phase; (b) establishment of a peripheral capsular vascular structure as a neoangiogenesis initiation site; (c) a peak in tumor vascularity that occurs before aggressive tumor growth; and (d) rapid tumor growth accompanied by decreasing vascularity. Microsurgical interventions mimicking local delivery of antiangiogenesis drugs were done by ligating arteries upstream from feeder vessels branching to the prostate. Microsurgery produced an immediate reduction of tumor blood flow, and flow remained low from 1 h to 2 weeks or longer after treatment. Power Doppler, in conjunction with micro-CT, showed that the tumors recruit secondary blood supplies from nearby vessels, which likely accounts for the continued growth of the tumors after surgery. The microsurgical model represents an advanced angiogenic prostate cancer stage in GEM mice corresponding to clinically defined hormone-refractory prostate cancer. Three-dimensional power Doppler imaging is completely noninvasive and will facilitate basic and preclinical research on neoangiogenesis in live animal models.

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography.

Abstract: Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 ± 0.03 ml) and functional residual capacity (0.16 ± 0.03 ml).

Optimization of a retrospective technique for respiratory-gated high speed micro-CT of free-breathing rodents

Abstract: The objective of this study was to develop a technique for dynamic respiratory imaging using retrospectively gated high-speed micro-CT imaging of free-breathing mice. Free-breathing C57Bl6 mice were scanned using a dynamic micro-CT scanner, comprising a flat-panel detector mounted on a slip-ring gantry. Projection images were acquired over ten complete gantry rotations in 50 s, while monitoring the respiratory motion in synchrony with projection-image acquisition. Projection images belonging to a selected respiratory phase were retrospectively identified and used for 3D reconstruction. The effect of using fewer gantry rotations?which influences both image quality and the ability to quantify respiratory function?was evaluated. Images reconstructed using unique projections from six or more gantry rotations produced acceptable images for quantitative analysis of lung volume, CT density, functional residual capacity and tidal volume. The functional residual capacity (0.15 ? 0.03 mL) and tidal volumes (0.08 ? 0.03 mL) measured in this study agree with previously reported measurements made using prospectively gated micro-CT and at higher resolution (150 ?m versus 90 ?m voxel spacing). Retrospectively gated micro-CT imaging of free-breathing mice enables quantitative dynamic measurement of morphological and functional parameters in the mouse models of respiratory disease, with scan times as short as 30 s, based on the acquisition of projection images over six gantry rotations.

Molecular and Histological Analysis of a New Rat Model of Experimental Knee Osteoarthritis

Abstract: Articular cartilage degeneration is the most consistently observed feature of osteoarthritis (OA). Animal and human studies have shown that various forms of exercise influence the course of the disease in different ways. In addition, early changes in articular cartilage that influence the progression of OA, such as the expression of cytokines, require further investigation. We have used a surgically induced experimental model of knee OA to address these questions. Here, we discuss our recent studies investigating the effects of an exercise paradigm in surgically induced OA, which determined that the destabilized knee joint is susceptible to enhanced degeneration when subjected to low-intensity, low-impact exercise. Further, we investigated early global changes in gene expression in articular chondrocytes from degenerating cartilage. Identified candidate genes including genes involved in chemokine, endothelin, and transforming growth factor-alpha signaling are discussed in the context of articular cartilage degeneration in early OA.

Micro-CT imaging of rat lung ventilation using continuous image acquisition during xenon gas contrast enhancement.

Abstract: We measured ventilation (V) in seven anesthetized, mechanically ventilated, supine Wistar rats. Images of the whole lung were continuously acquired using a dynamic, flat-panel volumetric micro-com...

A Device for Real-Time Measurement of Catheter-Motion and Input to a Catheter Navigation System

Abstract: Technological development of devices used in image-guided surgery and therapy has progressed due to the potential advantages such technology can bring to procedure efficacy and safety. This paper describes the technical design of a real-time catheter-motion sensor for use in investigating applied motion in catheter-based interventions and for use as an input device for a remote catheter navigation system. The device is comprised of three stages: the first two are passive stages used to measure axial and radial motion of the catheter and the third stage is an active brake used to impede motion. As a catheter is moved through the device, axial and radial measurement is achieved by mechanically coupling two optical encoders to the catheter. An electronic 24-bit counter and micro-controller are used to record incremental motion of the catheter. A computer loaded with a custom Python driver initializes and controls the micro-controller through a RS-232 port. The use of real clinical catheters with this device will allow the device to be used as an input to an image-guided remote catheter navigation system. User feedback may be achieved by linking a sensor in the slave device of a remote catheter navigation system, with the feedback system of the device.

Comparison of maximum intensity projection and digitally reconstructed radiographic projection for carotid artery stenosis measurement.

Abstract: Digital subtraction angiography is being supplanted by three-dimensional imaging techniques in many clinical applications, leading to extensive use of maximum intensity projection (MIP) images to depict volumetric vascular data. The MIP algorithm produces intensity profiles that are different than conventional angiograms, and can also increase the vessel-to-tissue contrast-to-noise ratio. We evaluated the effect of the MIP algorithm in a clinical application where quantitative vessel measurement is important: internal carotid artery stenosis grading. Three-dimensional computed rotational angiography (CRA) was performed on 26 consecutive symptomatic patients to verify an internal carotid artery stenosis originally found using duplex ultrasound. These volumes of data were visualized using two different postprocessing projection techniques: MIP and digitally reconstructed radiographic (DRR) projection. A DRR is a radiographic image simulating a conventional digitally subtracted angiogram, but it is derived computationally from the same CRA dataset as the MIP. By visualizing a single volume with two different projection techniques, the postprocessing effect of the MIP algorithm is isolated. Vessel measurements were made, according to the NASCET guidelines, and percentage stenosis grades were calculated. The paired t-test was used to determine if the measurement difference between the two techniques was statistically significant. The CRA technique provided an isotropic voxel spacing of 0.38 mm. The MIPs and DRRs had a mean signal-difference-to-noise-ratio of 30:1 and 26:1, respectively. Vessel measurements from MIPs were, on average, 0.17 mm larger than those from DRRs (P < 0.0001). The NASCET-type stenosis grades tended to be underestimated on average by 2.4% with the MIP algorithm, although this was not statistically significant (P=0.09). The mean interobserver variability (standard deviation) of both the MIP and DRR images was 0.35 mm. It was concluded that the MIP algorithm slightly increased the apparent dimensions of the arteries, when applied to these intra-arterial CRA images. This subpixel increase was smaller than both the voxel size and interobserver variability, and was therefore not clinically relevant.

Recent flow analysis studies in vascular models using doppler ultrasound

Abstract: Vascular disease is a major source of morbidity and mortality in Western society, with stroke and heart attacks accounting for about one third of deaths in North America. The carotid artery, and in particular the carotid bifurcation, is recognized as a common source of stroke-causing emboli that travel up into the brain, thereby blocking local blood flow. This has led to an emphasis on diagnostic techniques for assessing stroke risk due to carotid artery disease. Doppler ultrasound (DUS) techniques, in particular, uniquely enable visualization of flow patterns and characterization of various flow parameters. To improve our understanding of how blood-flow velocity patterns are modified as a result of disease in the carotid artery, basic research is typically carried out in physiologically realistic vascular models. In this paper, we review the progress that has been made in the development of ultrasound-compatible vascular models, as well as demonstrate the capabilities of DUS to quantify velocity patterns, turbulence, and recirculation. Ultrasound-compatible flow systems have been developed to mimic the geometry and hemodynamics of the carotid artery, under normal conditions and at various stages of narrowing due to atherosclerosis. These in vitro systems provide a controlled environment for developing new diagnostic techniques and for investigating and characterizing blood flow using DUS. Example data are shown from vessels with both eccentric and concentric stenoses, and in stenosed vessels that have been altered by the introduction of medical devices (stents) or additional roughness (ulceration). These results demonstrate the capacity for conventional clinical Doppler ultrasound devices to provide precise measurements of blood velocity from small sample volumes within a vessel, in order to build up detailed flow maps near and downstream of vascular disease or interventional device.

Assessment of Human Trabecular Architecture in the Pubis by Three Radiographic Modalities

Abstract: This poster discusses technical aspects of an investigation into the use of non-destructive radiological analyses of pubic cancellous bone structure to estimate age-at-death from human skeletal remains. This study stems from findings, in X-ray plain films, of increased rarification and orientation of trabeculae with age [1]; likely in concert with the macroscopic rem odelling of the symphyseal surface currently used in estimation of age-at-death.

R e c e n t Fl o w A n a l y s is St u d ie s in Va s c u l a r M o d e l s U s in g D o p p l e r Ul t r a s o u n d

Abstract: a b s t r a c t Vascular disease is a major source of morbidity and mortality in Western society, with stroke and heart attacks accounting for about one third of deaths in North America. The carotid artery, and in particular the carotid bifurcation, is recognized as a common source of stroke-causing emboli that travel up into the brain, thereby blocking local blood flow. This has led to an emphasis on diagnostic techniques for assessing stroke risk due to carotid artery disease. Doppler ultrasound (DUS) techniques, in particular, uniquely enable vi­ sualization o f flow patterns and characterization o f various flow parameters. To improve our understanding of how blood-flow velocity patterns are modified as a result of disease in the carotid artery, basic research is typically carried out in physiologically realistic vascular models. In this paper, we review the progress that has been made in the development of ultrasound-compatible vascular models, as well as demonstrate the capabilities of DUS to quantify velocity patterns, turbulence, and recirculation. Ultrasound-compatible flow systems have been developed to mimic the geometry and hemodynamics of the carotid artery, under normal conditions and at various stages of narrowing due to atherosclerosis. These in vitro systems provide a controlled environment for developing new diagnostic techniques and for investigating and characterizing blood flow using DUS. Example data are shown from vessels with both eccentric and concentric stenoses, and in stenosed vessels that have been altered by the introduction of medical devices (stents) or additional roughness (ulceration). These results demonstrate the capacity for conventional clinical Doppler ultrasound devices to provide precise measurements of blood velocity from small sample volumes within a vessel, in order to build up detailed flow maps near and downstream o f vascular disease or interventional device.

Off-line recording and analysis of Doppler velocity waveform data

Abstract: Doppler ultrasound velocity measurements are commonly used to diagnose atherosclerotic carotid artery disease. However, current Doppler techniques exhibit limitations with respect to sensitivity and specificity. We believe that advanced spectral analysis - including quantification of turbulence - could increase the diagnostic accuracy of duplex Doppler ultrasound. Routine application of advanced spectral analysis requires a practical technique to acquire and analyze the Doppler signal, which is compatible with clinical ultrasound machines. We describe the implementation of a technique for offline Doppler waveform analysis of carotid artery blood flow, using a portable MP3 recorder and custom analysis software. Forward and reverse audio signals were recorded with compression at 128 bps at prescribed points throughout the carotid bifurcation of human volunteers. Each data set was digitized at 44.1kHz and analyzed to produce velocity spectra at 12 ms intervals. From these instantaneous spectra, advanced Doppler indices of mean velocity and Fourier-based turbulence intensity (TI) were calculated. We found that MP3 compression had a negligible effect on the calculation of mean velocity data (0.17%) and TI (0.5%). We also found that Fourier-based TI was comparable to TI calculated by ensemble average. Finally, we were successful in applying this technique in vivo and demonstrated that long acquisitions and repeated measurements were possible in human volunteers. Our study demonstrates that it is feasible to acquire Doppler audio data using an MP3 recording device for off-line analysis, while only adding a short time to a conventional carotid exam.