Steven M. Jorgensen

Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT

A microcomputed tomography (micro-CT) scanner, which generates three-dimensional (3-D) images consisting of up to a billion cubic voxels, each 5-25 micron on a side, and which has isotropic spatial resolution, is described. Its main components are a spectroscopic X-ray source that produces selectable primary emission peaks at approximately 9, 18, or 25 keV and a fluorescing thin crystal plate that is imaged (at selectable magnification) with a lens onto a 2.5 x 2.5-cm, 1,024 x 1,024-pixel, charge-coupled device (CCD) detector array. The specimen is positioned close to the crystal and is rotated in 721 equiangular steps around 360 degrees between each X-ray exposure and its CCD recording. Tomographic reconstruction algorithms, applied to these recorded images, are used to generate 3-D images of the specimen. The system is used to scan isolated, intact, fixed rodent organs (e.g., heart or kidney) with the image contrast of vessel lumens enhanced with contrast medium. 3-D image display and analysis are used to address physiological questions about the internal structure-to-function relationships of the organs.

Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array

This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x-ray photon flux.

Quantitative X-ray imaging of intraplaque hemorrhage in aortas of apoE(-/-)/LDL(-/-) double knockout mice.

Objectives:To determine if hemorrhage into an arterial wall can be detected in CT images by virtue of the iron content. Materials and Methods:Aortas from male apoE−/−/LDL−/− mice (n = 31) were infused in situ with contrast agent, for micro-CT scanning and histology. Roentgen-opacities within the aortic walls were identified by histology and micro-x-ray fluorescence to be iron or calcium. Dual-energy scanning was performed at 2 energy levels using synchrotron-based micro-CT [(2 &mgr;m)3 voxels, 16 and 20 keV] and 64-slice CT (0.4 × 0.4 × 0.6 mm voxels, 80 and 120 kVp). Results:Opacities were identified as hemorrhage-related clusters of multiple punctate deposits, containing both Fe (0.48 × 10−12 g/voxel) and Ca (3.18 × 10−2 g/voxel), or as isolated confluent accumulations of exclusively calcium. Subtraction of the dual-energy CT scans discriminated iron from calcium deposits. Conclusion:Detection and quantification of iron deposits in hemorrhaged atherosclerotic lesions is feasible by dual-energy CT imaging.

Visualization of Three-Dimensional Nephron Structure With Microcomputed Tomography

The three‐dimensional architecture of nephrons in situ and their interrelationship with other nephrons are difficult to visualize by microscopic methods. The present study uses microcomputed X‐ray tomography (micro‐CT) to visualize intact nephrons in situ. Rat kidneys were perfusion‐fixed with buffered formalin and their vasculature was subsequently perfused with radiopaque silicone. Cortical tissue was stained en bloc with osmium tetroxide, embedded in plastic, scanned, and reconstructed at voxel resolutions of 6, 2, and 1 μm. At 6 μm resolution, large blood vessels and glomeruli could be visualized but nephrons and their lumens were small and difficult to visualize. Optimal images were obtained using a synchrotron radiation source at 2 μm resolution where nephron components could be identified, correlated with histological sections, and traced. Proximal tubules had large diameters and opaque walls, whereas distal tubules, connecting tubules, and collecting ducts had smaller diameters and less opaque walls. Blood vessels could be distinguished from nephrons by the luminal presence of radiopaque silicone. Proximal tubules were three times longer than distal tubules. Proximal and distal tubules were tightly coiled in the outer cortex but were loosely coiled in the middle and inner cortex. The connecting tubules had the narrowest diameters of the tubules and converged to form arcades that paralleled the radial vessels as they extended to the outer cortex. These results illustrate a potential use of micro‐CT to obtain three‐dimensional information about nephron architecture and nephron interrelationships, which could be useful in evaluating experimental tubular hypertrophy, atrophy, and necrosis. Anat Rec, 2007.

Anatomic Changes in Schlemm's Canal and Collector Channels in Normal and Primary Open-Angle Glaucoma Eyes Using Low and High Perfusion Pressures

PURPOSE To examine the anatomy of Schlemms canal (SC) and collector channels (CCs) in normal human and primary open-angle glaucoma (POAG) eyes under low and high perfusion pressure. METHODS In normal (n = 3) and POAG (n = 3) eye pairs, one eye was perfused at 10 mm Hg while the fellow eye was perfused at 20 mm Hg for 2 hours. Eyes were perfusion fixed at like pressures, dissected into quadrants, embedded in Epon Araldite, and scanned by three-dimensional micro-computed tomography (3D micro-CT). Schlemms canal volume, CC orifice area, diameter, and number were measured using ANALYZE software. RESULTS Normal eyes showed a larger SC volume (3.3-fold) and CC orifice area (9962.8 vs. 8825.2 μm(2)) and a similar CC diameter (34.3 ± 17.8 vs. 32.7 ± 13.0 μm) at 10 mm Hg compared to 20 mm Hg. In POAG eyes, SC volume (2.0-fold), CC orifice area (8049.2 μm(2)-6468.4 μm(2)), and CC diameter (36.2 ± 19.1 vs. 29.0 ± 13.8 μm) were increased in 10 mm Hg compared to 20 mm Hg perfusion pressures. Partial and total CC occlusions were present in normal and POAG eyes, with a 3.7-fold increase in total occlusions in POAG eyes compared to normal eyes at 20 mm Hg. Visualization of CCs increased by 24% in normal and by 21% in POAG eyes at 20 mm Hg compared to 10 mm Hg. Schlemms canal volume, CC area, and CC diameter were decreased in POAG eyes compared to normal eyes at like pressures. CONCLUSIONS Compensatory mechanisms for transient and short periods of increased pressure appear to be diminished in POAG eyes. Variable response to pressure change in SC and CCs may be a contributing factor to outflow facility change in POAG eyes.

Human Imaging With Photon Counting-Based Computed Tomography at Clinical Dose Levels: Contrast-to-Noise Ratio and Cadaver Studies.

ObjectivesThe purpose of this work was to measure and compare the iodine contrast-to-noise ratio (CNR) between a commercial energy-integrating detector (EID) computed tomography (CT) system and a photon-counting detector (PCD) CT scanner capable of human imaging at clinical dose rates, as well as to determine clinical feasibility using human cadavers. Materials and MethodsA research dual-source PCD-CT scanner was used, where the “A” tube/detector subsystem used an EID and the “B” tube/detector subsystem used a PCD. Iodine CNR was measured in 4 anthropomorphic phantoms, simulating 4 patient sizes, at 4 tube potential settings. After biospecimen committee approval, PCD scans were performed on a fresh-frozen human head and a whole-body cadaver using clinical dose rates. Scans were repeated using the EID and identical parameters, and qualitative side-by-side comparisons were performed. ResultsFor the same photon fluence, phantom measurements demonstrated a mean increase in CNR of 11%, 23%, 31%, 38% for the PCD system, relative to the EID system, at 80, 100, 120, and 140 kV, respectively. Photon-counting detector CT additionally provided energy-selective imaging, where low- and high-energy images reflected the energy dependence of the iodine signal. Photon-counting detector images of cadaveric anatomy demonstrated decreased beam hardening and calcium blooming in the high-energy bin images and increased contrast in the low-energy bins images relative to the EID images. Threshold-based PCD images were qualitatively deemed equivalent in other aspects. ConclusionsThe evaluated research PCD-CT system was capable of clinical levels of image quality at clinical dose rates. It further provided improved CNR relative to state-of-the-art EID-CT. The energy-selective bin images provide further opportunity for dual-energy and multienergy analyses.

3D architecture of myocardial microcirculation in intact rat heart: a study with micro-CT.

The branching geometry of the coronary arterial tree may play a significant role in the observed spatial heterogeneity in myocardial perfusion. To provide more insight into this possibility we used a micro-CT scanner to image the intact rat heart and its opacified coronary arterial tree, for quantitative analysis of the coronary arterial architecture. Results show a consistent pattern of branching throughout the heart wall.

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.

A technical solution to avoid partial scan artifacts in cardiac MDCT

Quantitative evaluation of cardiac image data obtained using multidetector row computed tomography (CT) is compromised by partial scan reconstructions, which improve the temporal resolution but significantly increase image-to-image CT number variations for a fixed region of interest compared to full reconstruction images. The feasibility of a new approach to solve this problem is assessed. An anthropomorphic cardiac phantom and an anesthetized pig were scanned on a dual-source CT scanner using both full and partial scan acquisition modes under different conditions. Additional scans were conducted with the electrocardiogram (ECG) signal being in synchrony with the gantry rotation. In the animal study, a simple x-ray detector was used to generate a signal once per gantry rotation. This signal was then used to pace the pigs heart. Phantom studies demonstrated that partial scan artifacts are strongly dependent on the rotational symmetry of angular projections, which is determined by the object shape and composition and its position with respect to the isocenter. The degree of partial scan artifacts also depends on the location of the region of interest with respect to highly attenuating materials (bones, iodine, etc.) within the object. Single-source partial scan images (165 ms temporal resolution) were significantly less affected by partial scan artifacts compared to dual-source partial scan images (82 ms temporal resolution). When the ECG signal was in synchrony with the gantry rotation, the same cardiac phase always corresponded to the same positions of the x-ray tube(s) and, hence, the same scattering and beam hardening geometry. As a result, the range of image-to-image CT number variations for partial scan reconstruction images acquired in synchronized mode was decreased to that achieved using full reconstruction image data. The success of the new approach, which synchronizes the ECG signal with the position of the x-ray tube(s), was demonstrated both in the phantom and animal experiments.

Initial results from a prototype whole-body photon-counting computed tomography system.

X-ray computed tomography (CT) with energy-discriminating capabilities presents exciting opportunities for increased dose efficiency and improved material decomposition analyses. However, due to constraints imposed by the inability of photon-counting detectors (PCD) to respond accurately at high photon flux, to date there has been no clinical application of PCD-CT. Recently, our lab installed a research prototype system consisting of two x-ray sources and two corresponding detectors, one using an energy-integrating detector (EID) and the other using a PCD. In this work, we report the first third-party evaluation of this prototype CT system using both phantoms and a cadaver head. The phantom studies demonstrated several promising characteristics of the PCD sub-system, including improved longitudinal spatial resolution and reduced beam hardening artifacts, relative to the EID sub-system. More importantly, we found that the PCD sub-system offers excellent pulse pileup control in cases of x-ray flux up to 550 mA at 140 kV, which corresponds to approximately 2.5×1011 photons per cm2 per second. In an anthropomorphic phantom and a cadaver head, the PCD sub-system provided image quality comparable to the EID sub-system for the same dose level. Our results demonstrate the potential of the prototype system to produce clinically-acceptable images in vivo.