We describe a set of methods to enable fully automated analysis of a novel label-free spinning-disc format microarray
system. This microarray system operates in a dual-channel mode, simultaneously acquiring fluorescence as well as
interferometric signals. The label-free interferometric component enables the design of robust gridding methods, which
account for rotational effects difficult to estimate in traditional microarray image analysis. Printing of microarray
features in a Cartesian grid is preferable for commercial systems because of the benefits of using existing DNA/protein
printing technologies. The spinning disc operation of the microarray requires spatial transformation of Cartesian
microarray features, from the reader/scanner frame of reference to the disc frame of reference. We describe a fast spatial
transformation method with no measurable degradation in the quality of transformed data, for this purpose. The gridding
method uses frequency-domain information to calculate grid spacing and grid rotation. An adaptive morphological
segmentation method is used to segment microarray spots with variable sizes accurately. The entire process, from the
generation of the raw data to the extraction of biologically relevant information, can be performed without any manual
intervention, allowing for the deployment of high-throughput systems. These image analysis methods have enabled this
microarray system to achieve superior sensitivity limits.
Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52±1.70mL (p<0.002) at expiration and 4.77±3.34mL (p<0.03) at inspiration. The mean lung densities of emphysema rats decreased by 91.76±68.11HU (p<0.01) at expiration and low attenuation areas increased by 5.21±3.88% (p<0.04) at inspiration compared with normal rats. The perfusion for normal and emphysema rats were 0.25±0.04ml/s/ml and 0.32±0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21±0.04 and 0.15±0.02. There was a trend toward faster MTTs for emphysema rats (0.42±0.08s) than normal rats (0.89±0.19s) with p<0.006, suggesting that blood flow crossing the capillaries increases as the capillary volume decreases and which may cause the red blood cells to leave the capillaries incompletely saturated with oxygen if the MTTs become too short. Conclusion: Quantitative measurement using CT of structural and functional changes in pulmonary emphysema appears promising for small animals.
High-speed X-ray computed tomography (CT) has the potential to observe the transport of iodinated radio-opaque contrast agent (CA) through tissue enabling the quantification of tissue physiology in organs and tumors. The concentration of Iodine in the tissue and in the left ventricle is extracted as a function of time and is fit to a compartmental model for physiologic parameter estimation. The reproducibility of the physiologic parameters depend on the (1) The image-sampling rate. According to our simulations 5-second sampling is required for CA injection rates of 1.0ml/min (2) the compartmental model should reflect the real tissue function to give meaning results. In order to verify these limits a functional CT study was carried out in a group of 3 mice. Dynamic CT scans were performed on all the mice with 0.5ml/min, 1ml/min and 2ml/min CA injection rates. The physiologic parameters were extracted using 4 parameter and 6 parameter two compartmental models (2CM). Single factor ANOVA did not indicate a significant difference in the perfusion, in the kidneys for the different injection rates. The physiologic parameter obtained using the 6-parameter 2CM model was in line with literature values and the 6-parameter significantly improves chi-square goodness of fits for two cases.
Micro-computed tomography (microCT) is capable of obtaining high-resolution images of skeletal tissues. However its image contrast among soft tissues remains inadequate for tumor detection. High speed functional computed tomography will be needed to image tumors by employing x-ray contrast medium. The functional microCT development will not only facilitate the image contrast enhancement among different tissues but also provide information of tumor physiology. To demonstrate the feasibility of functional CT in mouse imaging, sequential computed tomography is performed in mice after contrast material administration using a high-speed clinical CT scanner. Although the resolution of the clinical scanner is not sufficient to dissolve the anatomic details of rodents, bulky physiological parameters in major organs such as liver, kidney, pancreas, and ovaries (testicular) can be examined. For data analysis, a two-compartmental model is employed and implemented to characterize the tissue physiological parameters (regional blood flow, capillary permeability, and relative compartment volumes.) The measured contrast dynamics in kidneys are fitted with the compartmental model to derive the kidney tissue physiology. The study result suggests that it is feasible to extract mouse tissue physiology using functional CT imaging technology.
Subsecond multi-slice spiral CT has now been recognized with its great potential in cardiac imaging, in particularly for the coronary calcification detection (CCD). Different reconstruction algorithms have been developed in order to optimize the temporal resolution and to improve the measurement accuracy. These algorithms typically incorporate retrospectively gated reconstructions based on a synchronized electrocardiography (ECG) recording. However, these algorithms consist of different approaches in choosing spatial filters, setting ECG delays, and employing the reconstruction geometry (direct fan-beam vs. parallel rebining). These differences are likely to contribute to the intrascanner and interscanner variability in the coronary calcium measurements. This paper investigates in detail about the quantitative effect on calcium detection among different approaches.
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