Diane R. Eaker

Algorithm-Enabled Low-Dose Micro-CT Imaging

Micro-computed tomography (micro-CT) is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300-1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging.

Synchrotron‐Based Micro‐CT Imaging of the Human Lung Acinus

Structural data about the human lung fine structure are mainly based on stereological methods applied to serial sections. As these methods utilize 2D images, which are often not contiguous, they suffer from inaccuracies which are overcome by analysis of 3D micro‐CT images of the never‐sectioned specimen. The purpose of our study was to generate a complete data set of the intact three‐dimensional architecture of the human acinus using high‐resolution synchrotron‐based micro‐CT (synMCT). A human lung was inflation‐fixed by formaldehyde ventilation and then scanned in a 64‐slice CT over its apex to base extent. Lung samples (8‐mm diameter, 10‐mm height, N = 12) were punched out, stained with osmium tetroxide, and scanned using synMCT at (4 μm)3 voxel size. The lung functional unit (acinus, N = 8) was segmented from the 3D tomographic image using an automated tree‐analysis software program. Morphometric data of the lung were analyzed by ANOVA. Intra‐acinar airways branching occurred over 11 generations. The mean acinar volume was 131.3 ± 29.2 mm3 (range, 92.5–171.3 mm3) and the mean acinar surface was calculated with 1012 ± 26 cm2. The airway internal diameter (starting from the bronchiolus terminalis) decreases distally from 0.66 ± 0.04 mm to 0.34 ± 0.06 mm (P < 0.001) and remains constant after the seventh generation (P < 0.5). The length of each generation ranges between 0.52 and 0.93 mm and did not show significant differences between the second and eleventh generation. The branching angle between daughter branches varies between 113‐degree and 134‐degree without significant differences between the generations (P < 0.3). This study demonstrates the feasibility of quantitating the 3D structure of the human acinus at the spatial resolution readily achievable using synMCT. Anat Rec 293:1607–1614, 2010.

IVUS Detection of Vasa Vasorum Blood Flow Distribution in Coronary Artery Vessel Wall

There is an increased body of evidence to suggest that the vasa vasorum play a major role in the progression and complications of vulnerable plaque leading to acute coronary syndrome. We propose that detecting changes in the flow in the vascular wall by intravascular ultrasound signals can quantify the presence of vasa vasorum. The results obtained in a porcine model of atherosclerosis suggest that intravascular ultrasound-based estimates of blood flow in the arterial wall can be used in vivo in a clinical research setting to establish the density of vasa vasorum as an indicator of plaque vulnerability.

Quantification of vasa vasorum density in multi-slice computed tomographic coronary angiograms: role of computed tomographic image voxel size.

Objective: This study is motivated by the possibility of using computed tomography (CT) to detect early coronary atherosclerosis by the increased CT values within the arterial wall resulting from vasa vasorum proliferation. Methods: Coronary arteries (n = 5) with early atherosclerotic changes were injected with Microfil and scanned (micro-CT). Noise was added to the CT projection data sets (to represent the radiation exposure of current clinical CT scanners) and then reconstructed to generate 3-dimensional images at different voxel sizes. Results: Higher CT values were detected because of contrast agent in vasa vasorum if voxel size was less than (150 &mgr;m)3. Contrast in the main lumen increased the CT values dramatically at voxels greater than (100 &mgr;m)3, whereas CT values of the same specimen without contrast in the main lumen remained constant. Conclusions: Voxel sizes less than (200 &mgr;m)3 are needed to quantitate arterial wall opacification due to vasa vasorum proliferation.

Reproducibility of Global and Local Reconstruction of Three-Dimensional Micro-Computed Tomography of Iliac Crest Biopsies

Variation in computed tomography (CT) image grayscale and spatial geometry due to specimen orientation, magnification, voxel size, differences in X-ray photon energy and limited field-of-view during the scan, were evaluated in repeated micro-CT scans of iliac crest biopsies and test phantoms. Using the micro-CT scanner on beamline X2B at the Brookhaven National Laboratorys National Synchrotron Light Source, 3-D micro-CT images were generated. They consisted of up to 1024 X 24002, 4-mum cubic voxels, each with 16-bit gray-scale. We also reconstructed the images at 16-, 32-, and 48-mum voxel resolution. Scan data were reconstructed from the complete profiles using filtered back-projection and from truncated profiles using profile-extension and with a Local reconstruction algorithm. Three biopsies and one bonelike test phantom were each rescanned at three different times at annual intervals. For the full-data-set reconstructions, the reproducibility of the estimates of mineral content of bone at mean bone opacity value, was plusmn28.8 mg/cm3 , i.e., 2.56%, in a 4-mum cubic voxel at the 95% confidence level. The reproducibility decreased with increased voxel size. The interscan difference in imaged bone volume ranged from 0.86 plusmn 0.64% at 4-mum voxel resolution, and 2.64 plusmn 2.48% at 48 mum.

Direct three-dimensional coherently scattered x-ray microtomography

PURPOSE It has been shown that coherently scattered x rays can be used to discriminate and identify specific components in a mixture of low atomic weight materials. The authors demonstrated a new method of doing coherently scattered x-ray tomography with a thin sheet of x ray. METHODS A collimated x-ray fan-beam, a parallel polycapillary collimator, and a phantom consisting of several biocompatible materials of low attenuation-based contrast were used to investigate the feasibility of the method. Because of the particular experimental setup, only the phantom translation perpendicular to the x-ray beam is needed and, thus, there is no need of Radon-type tomographic reconstruction, except for the correction of the attenuation to the primary and scattered x rays, which was performed by using a conventional attenuation-based tomographic image data set. The coherent scatter image contrast changes with momentum transfer among component materials in the specimen were investigated with multiple x-ray sources with narrow bandwidth spectra generated with anode and filter combinations of Cu/Ni (8 keV), Mo/Zr (18 keV), and Ag/Pd (22 keV) and at multiple scatter angles by orienting the detector and polycapillary collimator at different angles to the illuminating x ray. RESULTS The contrast among different materials changes with the x-ray source energy and the angle at which the image was measured. The coherent scatter profiles obtained from the coherent scatter images are consistent with the published results. CONCLUSIONS This method can be used to directly generate the three-dimensional coherent scatter images of small animal, biopsies, or other small objects with low atomic weight biological or similar synthetic materials with low attenuation contrast. With equipment optimized, submillimeter spatial resolution may be achieved.

Micro-CT as a guide for clinical CT development

Micro-CT, with voxel size ~10-5 mm3, has a great advantage over traditional microscopic methods in its ability to generate detailed 3D images in relatively large, opaque, volumes such as an intact mouse femur, heart or kidney. In addition to providing new insights into tissue structure-to-function interrelationships, micro-CT can contribute to suggesting new applications of clinical CT imaging such as: A. The spatio-density-temporal resolution that is needed to: 1) Quantitate an organs Basic Functional Unit (smallest collection of diverse cells that behaves like the organ), which requires voxels less than 10-4 mm3 in volume; 2) Quantitate new vessel growth which manifests as increased x-ray contrast enhancement in tissues during passage of a bolus of intravascular contrast agent; 3) Quantitate endothelial integrity by the movement of x-ray contrast agents across the endothelial inner lining of vessel walls. B. The use of x-ray scatter for providing the contrast amongst soft tissue components and/or their interfaces for enhanced discrimination of nerve and muscular/tendon fiber directions.

A polycapillary x-ray optics-based integrated micro-SPECT/CT scanner

To show the feasibility of a combined micro-CT and micro-SPECT scanner based on use of polycapillary optics we inserted an optic between the radio-labeled specimen and our micro-CT scanners imaging system. The micro-CT x-ray focal spot was placed at the focal point of the optic so that x-ray micro-CT of the specimen could also be performed without having to move the specimen. Using this set-up we scanned a 2 cm diameter Plexiglas cylinder with three (177 μCi) prostate brachytherapy seeds embedded in it. Each seed was 0.5 mm diameter, 4 mm long and filled with 0.4 mm diameter ceramic beads coated with 125Iodine. The SPECT images clearly resolve the layer of 125Iodine on the beads. That the SPECT image is spatially correct was cofirmed by the concurrent CT image. We also used a parallel polycapillary optic to scan a 1.5 cm Plexiglas cylinder with holes (2, 1, and 0.5 mm diameter, parallel to the cylinder axis) filled with a solution containing 11.56μCi/mm3 of 125Iodine. These data indicate a spatial resolution of 5 line pairs per mm at 10% modulation. Based on these results we propose a design that is more efficient at acquiring the scintigraphic image data.

Coherent x-ray scattering for discriminating bio-compatible materials in tissue scaffolds

It has been shown that coherently scattered x-rays can be used to discriminate and identify specific components in a mixture of materials. To assess the feasibility of using coherent x-ray scatter (CXS) to characterize the material components within tissue scaffolds, we studied the CXS properties of the bio-compatible materials of polymers (polypropylene fumarate, polycaprolactone, epoxy, etc.), sugar and salt solutions at different concentration, and complex materials consisting of more than one polymer. We also investigated the effects of x-ray spectra on the CXS functions of polymers by measuring them with different x-ray source anodes. It is shown that the synthesized polymers with different portions of base polymers can be characterized with CXS. The polymerization process does not significantly change the CXS characteristics of the measured polymers. When protein is denatured, no substantial change in scatter was detected. Solutions of different concentration can be characterized and quantified by the CXS features corresponding to the solutes. The difference among CXS of solutions of different concentration makes it possible to image and trace fluids and their concentration changes in tissues or scaffolds. Our results show that CXS of complex specimens can be decomposed with the scatter functions of the component materials. By simulating a tissue scaffold with a phantom with several bio-compatible materials, we demonstrated that significant contrast can be achieved at proper scatter angles by measuring the coherent x-ray scatter, despite the low attenuation-based contrast between them. We conclude that use of x-ray scatter makes it possible to track and map the fate (e.g., its breakdown and/or removal) of specific components within tissue scaffolds.

Tomographic imaging of coherent x-ray scatter momentum transfer distribution using spectral x-ray detection and polycapillary optic

Quantitation of coherent x-ray scatter traditionally involves measuring the intensity of the scattered x-ray over a range of angles (θ) from the illuminating monochromatic x-ray beam. Spectral x-ray imaging produces the same information at a single θ when bremsstrahlung x-ray exposure is used. We used a 200μm thick sheet-illumination of a phantom (lucite cylinder containing holes with water, polyethylene, collagen, polycarbonate, and nylon) and a polycapillary x-ray optic collimator to provide measurements at a fixed θ. A Medipix2 x-ray detection array (2562 (55μm)2 pixels) provided the spectral (E, 10 - 22 keV in 3keV energy bins) spread needed to generate the momentum transfer (q) profile information at one angle. The tungsten x-ray source anode (aluminum filter) was operated at 35kVp at 20mA. The detected scatter intensity was corrected for attenuation of the incident and the scattered x-ray by use of the regular CT image of the phantom generated at the same energy bins. The phantom was translated normal to the plane of the fan beam in 65, 0.2mm, steps to generate the 3D image data. The momentum transfer profiles generated with this approach were compared to published momentum transfer profiles obtained by other methods.