How Low Can We Go in Radiation Dose for the Data-Completion Scan on a Research Whole-Body Photon-Counting Computed Tomography System.

PURPOSE: A research photon-counting computed tomography (CT) system that consists of an energy-integrating detector (EID) and a photon-counting detector (PCD) was installed in our laboratory. The scanning fields of view of the EID and PCD at the isocenter are 500 and 275 mm, respectively. When objects are larger than the PCD scanning field of view, a data-completion scan (DCS) using the EID subsystem is needed to avoid truncation artifacts in PCD images. The goals of this work were to (1) find the impact of a DCS on noise of PCD images and (2) determine the lowest possible dose for a DCS such that truncation artifacts are negligible in PCD images. METHODS: First, 2 semianthropomorphic abdomen phantoms were scanned on the PCD subsystem. For each PCD scan, we acquired 1 DCS with the maximum effective mAs and 5 with lower effective mAs values. The PCD image reconstructed using the maximum effective mAs was considered as the reference image, and those using the lower effective mAs as the test images. The PCD image reconstructed without a DCS was considered the baseline image. Each PCD image was assessed in terms of noise and CT number uniformity; the results were compared among the baseline, test, and reference images. Finally, the impact of a DCS on PCD image quality was qualitatively assessed for other body regions using an anthropomorphic torso phantom. RESULTS: The DCS had a negligible impact on the noise magnitude in the PCD images. The PCD images with the minimum available dose (CTDIvol < 2 mGy) showed greatly enhanced CT number uniformity compared with the baseline images without noticeable truncation artifacts. Further increasing the effective mAs of a DCS did not yield noticeable improvement in CT number uniformity. CONCLUSIONS: A DCS using the minimum available dose had negligible effect on image noise and was sufficient to maintain satisfactory CT number uniformity for the PCD scans.

Anatomy of hepatic arteriolo-portal venular shunts evaluated by 3D micro-CT imaging.

The liver differs from other organs in that two vascular systems deliver its blood - the hepatic artery and the portal vein. However, how the two systems interact is not fully understood. We therefore studied the microvascular geometry of rat liver hepatic artery and portal vein injected with the contrast polymer Microfil(®). Intact isolated rat livers were imaged by micro-CT and anatomic evidence for hepatic arteriolo-portal venular shunts occurring between hepatic artery and portal vein branches was found. Simulations were performed to rule out the possibility of the observed shunts being artifacts resulting from image blurring. In addition, in the case of specimens where only the portal vein was injected, only the portal vein was opacified, whereas in hepatic artery injections, both the hepatic artery and portal vein were opacified. We conclude that mixing of the hepatic artery and portal vein blood can occur proximal to the sinusoidal level, and that the hepatic arteriolo-portal venular shunts may function as a one-way valve-like mechanism, allowing flow only from the hepatic artery to the portal vein (and not the other way around).

Vascularity of myocardium and gastrocnemius muscle in rats selectively bred for endurance running capacity.

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculature's branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.

Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of polycystic kidney and liver disease.

BACKGROUND & AIMS: In polycystic kidney disease and polycystic liver disease (PLD), the normally nonproliferative hepato-renal epithelia acquire a proliferative, cystic phenotype that is linked to overexpression of cell division cycle 25 (Cdc25)A phosphatase and cell-cycle deregulation. We investigated the effects of Cdc25A inhibition in mice and rats via genetic and pharmacologic approaches. METHODS: Cdc25A(+/-) mice (which have reduced levels of Cdc25A) were cross-bred with polycystic kidney and hepatic disease 1 (Pkhd1(del2/del2)) mice (which have increased levels of Cdc25A and develop hepatic cysts). Cdc25A expression was analyzed in livers of control and polycystic kidney (PCK) rats, control and polycystic kidney 2 (Pkd2(ws25/-)) mice, healthy individuals, and patients with PLD. We examined effects of pharmacologic inhibition of Cdc25A with vitamin K3 (VK3) on the cell cycle, proliferation, and cyst expansion in vitro; hepato-renal cystogenesis in PCK rats and Pkd2(ws25/-)mice; and expression of Cdc25A and the cell-cycle proteins regulated by Cdc25A. We also examined the effects of the Cdc25A inhibitor PM-20 on hepato-renal cystogenesis in Pkd2(ws25/-) mice. RESULTS: Liver weights and hepatic and fibrotic areas were decreased by 32%-52% in Cdc25A(+/-):Pkhd1(del2/del2) mice, compared with Pkhd1(del2/del2) mice. VK3 altered the cell cycle and reduced proliferation of cultured cholangiocytes by 32%-83% and decreased growth of cultured cysts by 23%-67%. In PCK rats and Pkd2(ws25/-) mice, VK3 reduced liver and kidney weights and hepato-renal cystic and fibrotic areas by 18%-34%. PM-20 decreased hepato-renal cystogenesis in Pkd2(ws25/-) mice by 15%. CONCLUSIONS: Cdc25A inhibitors block cell-cycle progression and proliferation, reduce liver and kidney weights and cyst growth in animal models of polycystic kidney disease and PLD, and might be developed as therapeutics for these diseases.

Measurement of enhanced vasa vasorum density in a porcine carotid model using photon counting detector CT.

Purpose: The onset of atherosclerosis is preceded by changes in blood perfusion within the arterial wall due to localized proliferation of the vasa vasorum. The purpose of this study was to quantify these changes in spatial density of the vasa vasorum using a research whole-body photon-counting detector CT (PCD-CT) scanner and a porcine model. Approach: Vasa vasorum angiogenesis was stimulated in the left carotid artery wall of anesthetized pigs ( n = 5 ) while the right carotid served as a control. After a 6-week recovery period, the animals were scanned on the PCD-CT prior to and after injection of iodinated contrast. Annular regions of interest were used to measure wall enhancement in the injured and control arteries. The exact Wilcoxon-signed rank test was used to determine whether a significant difference in contrast enhancement existed between the injured and control arterial walls. Results: The greatest arterial wall enhancement was observed following contrast recirculation. The wall enhancement measurements made over these time points revealed that the enhancement was greater in the injured artery for 13/16 scanned arterial regions. Using an exact Wilcoxon-signed rank test, a significantly increased enhancement ratio was found in injured arteries compared with control arteries ( p = 0.013 ). Vasa vasorum angiogenesis was confirmed in micro-CT scans of excised arteries. Conclusions: Whole-body PCD-CT scanners can be used to detect and quantify the increased perfusion occurring within the porcine carotid arterial wall resulting from an increased density of vasa vasorum.

In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis.

Nephrolithiasis is a major public health problem with a complex and varied etiology. Most stones are composed of calcium oxalate (CaOx), with dietary excess a risk factor. Because of complexity of mammalian system, the details of stone formation remain to be understood. Here we have developed a nephrolithiasis model using the genetic model Drosophila melanogaster, which has a simple, transparent kidney tubule. Drosophilia reliably develops CaOx stones upon dietary oxalate supplementation, and the nucleation and growth of microliths can be viewed in real time. The Slc26 anion transporter dPrestin (Slc26a5/6) is strongly expressed in Drosophilia kidney, and biophysical analysis shows that it is a potent oxalate transporter. When dPrestin is knocked down by RNAi in fly kidney, formation of microliths is reduced, identifying dPrestin as a key player in oxalate excretion. CaOx stone formation is an ancient conserved process across >400 My of divergent evolution (fly and human), and from this study we can conclude that the fly is a good genetic model of nephrolithiasis.

Current status of developments and applications of micro-CT.

Use of microscopic computed-tomography (micro-CT) scanning continues to grow in biomedical research. Laboratory-based micro-CT scanners, laboratory-based nano-CT scanners, and integrated micro-CT/SPECT and micro-CT/PET scanners are now manufactured for "turn-key" operation by a number of commercial vendors. In recent years a number of technical developments in X-ray sources and X-ray imaging arrays have broadened the utility of micro-CT. Of particular interest are photon-counting and energy-resolving detector arrays. These are being explored to maximize micro-CT image grayscale dynamic range and to further increase image contrast by utilizing the unique spectral attenuation characteristics of individual chemical elements. X-ray phase-shift images may increase contrast resolution and reduce radiation exposure. Although radiation exposure is becoming a concern with the drive for increased spatial and temporal resolution, especially for longitudinal studies, gated scans and limited scan-data-set reconstruction algorithms show great potential for keeping radiation exposure to a minimum.

A strategy to decrease partial scan reconstruction artifacts in myocardial perfusion CT: phantom and in vivo evaluation.

PURPOSE: Partial scan reconstruction (PSR) artifacts are present in myocardial perfusion imaging using dynamic multidetector computed tomography (MDCT). PSR artifacts appear as temporal CT number variations due to inconsistencies in the angular data range used to reconstruct images and compromise the quantitative value of myocardial perfusion when using MDCT. The purpose of this work is to present and evaluate a technique termed targeted spatial frequency filtration (TSFF) to reduce CT number variations due to PSR when applied to myocardial perfusion imaging using MDCT. METHODS: The TSFF algorithm requires acquiring enough X-ray projections to reconstruct both partial (π + fan angle α) and full (2π) scans. Then, using spatial linear filters, the TSFF-corrected image data are created by superimposing the low spatial frequency content of the full scan reconstruction (containing no PSR artifacts, but having low spatial resolution and worse temporal resolution) with the high spatial frequency content of the partial scan reconstruction (containing high spatial frequencies and better temporal resolution). The TSFF method was evaluated both in a static anthropomorphic thoracic phantom and using an in vivo porcine model and compared with a previously validated reference standard technique that avoids PSR artifacts by pacing the animal heart in synchrony with the gantry rotation. CT number variations were quantified by measuring the range and standard deviation of CT numbers in selected regions of interest (ROIs) over time. Myocardial perfusion parameters such as blood volume (BV), mean transit time (MTT), and blood flow (BF) were quantified and compared in the in vivo study. RESULTS: Phantom experiments demonstrated that TSFF reduced PSR artifacts by as much as tenfold, depending on the location of the ROI. For the in vivo experiments, the TSFF-corrected data showed two- to threefold decrease in CT number variations. Also, after TSFF, the perfusion parameters had an average difference of 13.1% (range 4.5%-25.6%) relative to the reference method, in contrast to an average difference of 31.8% (range 0.3%-54.0%) between the non-TSFF processed data with the reference method. CONCLUSIONS: TSFF demonstrated consistent reduction in CT number variations due to PSR using controlled phantom and in vivo experiments. TSFF-corrected data provided quantitative measures of perfusion (BV, MTT, and BF) with better agreement to a reference method compared to noncorrected data. Practical implementation of TSFF is expected to incur in an additional radiation exposure of 14%, when tube current is modulated to 20% of its maximum, to complete the needed full scan reconstruction.

Intrinsic microvasculature of the sciatic nerve in the rat.

Microvasculature associated with the sciatic nerve was examined using high-resolution micro-CT scanning in one group of rats and surgical exploration in another. The results indicate that blood supply to the sciatic nerve is an "open-ended" system in which the vessels run longitudinally within the epineurium and connect with external vasculature primarily at junction points. Although the range of vasculature found extended down to 4-5 µ, only a few isolated vessels of this size were found, with no capillary "mesh" as such, possibly because of the close proximity of the intrinsic vessel to nerve fibers within the epineurium. While the study did not include direct measurements of flow or nerve function, the "open-ended" pattern of vasculature found has important implications regarding the relationship between the two. Specifically, the nerve is less vulnerable to a severe or complete disruption in blood supply than it would be under a close-ended system such as that of the heart or brain, where a severe disruption can occur with the obstruction of only a single vessel. Indeed, the pattern of vasculature found, subject to further study of vasculature at the capillary level, suggests that flow within the intrinsic vessels may be in either direction, depending on circumstances, somewhat like flow within the circle of Willis in the cerebral circulation.

Angioarchitectural changes in subacute cerebral venous thrombosis. A synchrotron-based micro- and nano-CT study.

It is well known that recanalization of thrombosed cerebral sinuses occurs early but without marked influence on the long-term outcome and on final venous infarct volume on magnetic resonance imaging. To better understand the possible microvascular mechanisms behind these clinical observations, we evaluated the sequels of subacute superior sagittal sinus (SSS) thrombosis in rats using micro- and nano-CT imaging of the same specimen to provide large volume and high resolution CT image data respectively. SSS thrombosis was induced in 11 animals which were euthanized after 6h (n=4) or 6 weeks (n=7). Eight sham-operated rats served as controls. After infusion of contrast into the vasculature of the brains, these were isolated and scanned using micro-, nano-, and synchrotron-based micro-CT ((8 µm³), (900 nm)³, and (1.9 µm³) voxel sizes). The cross-sectional area of the superior sagittal sinus, microvessels and cortical veins were quantified. Tissue sections were stained against VEGF antigen. Immunohistochemistry was confirmed using quantitative rtPCR. SSS thrombosis led to a congestion of the bridging veins after 6h. After 6 weeks, a network of small vessels surrounding the occluded SSS was present with concurrent return towards the diameter of the draining bridging veins of controls. This microvascular network connected to cortical veins as demonstrated by nano- and synchrotron-based micro-CT. Also the volume fraction and number of cortical veins increased significantly. Immunohistochemistry in the region of the microsvascular network demonstrated a strong immunoreactivity against VEGF, confirmed by rtPCR. The sequel of subacute SSS thrombosis induced a network of microvessels ("venogenesis") draining the bridging veins. Also the volume fraction of cortical veins increased significantly.

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization.

Myocardial microvascular permeability and coronary sinus concentration of muscle metabolites have been shown to increase after myocardial ischemia due to epicardial coronary artery occlusion and reperfusion. However, their association with coronary microembolization is not well defined. This study tested the hypothesis that acute coronary microembolization increases microvascular permeability in the porcine heart. The left anterior descending perfusion territories of 34 anesthetized pigs (32 ± 3 kg) were embolized with equal volumes of microspheres of one of three diameters (10, 30, or 100 µm) and at three different doses for each size. Electron beam computed tomography (EBCT) was used to assess in vivo, microvascular extraction of a nonionic contrast agent (an index of microvascular permeability) before and after microembolization with microspheres at baseline and during adenosine infusion. A high-resolution three-dimensional microcomputed tomography (micro-CT) scanner was subsequently used to obtain ex vivo, the volume and corresponding surface area of the embolized myocardial islands within the perfusion territories of the microembolized coronary artery. EBCT-derived microvascular extraction of contrast agent increased within minutes after coronary microembolization (P < 0.001 vs. baseline and vs. control values). The increase in coronary microvascular permeability was highly correlated to the micro-CT-derived total surface area of the nonperfused myocardium (r = 0.83, P < 0.001). In conclusion, myocardial extravascular accumulation of contrast agent is markedly increased after coronary microembolization and its magnitude is in proportion to the surface area of the interface between the nonperfused and perfused territories.

Imaging the aqueous humor outflow pathway in human eyes by three-dimensional micro-computed tomography (3D micro-CT).

The site of outflow resistance leading to elevated intraocular pressure in primary open-angle glaucoma is believed to be located in the region of Schlemm's canal inner wall endothelium, its basement membrane and the adjacent juxtacanalicular tissue. Evidence also suggests collector channels and intrascleral vessels may have a role in intraocular pressure in both normal and glaucoma eyes. Traditional imaging modalities limit the ability to view both proximal and distal portions of the trabecular outflow pathway as a single unit. In this study, we examined the effectiveness of three-dimensional micro-computed tomography (3D micro-CT) as a potential method to view the trabecular outflow pathway. Two normal human eyes were used: one immersion fixed in 4% paraformaldehyde and one with anterior chamber perfusion at 10 mmHg followed by perfusion fixation in 4% paraformaldehyde/2% glutaraldehyde. Both eyes were postfixed in 1% osmium tetroxide and scanned with 3D micro-CT at 2 µm or 5 µm voxel resolution. In the immersion fixed eye, 24 collector channels were identified with an average orifice size of 27.5 ± 5 µm. In comparison, the perfusion fixed eye had 29 collector channels with a mean orifice size of 40.5 ± 13 µm. Collector channels were not evenly dispersed around the circumference of the eye. There was no significant difference in the length of Schlemm's canal in the immersed versus the perfused eye (33.2 versus 35.1 mm). Structures, locations and size measurements identified by 3D micro-CT were confirmed by correlative light microscopy. These findings confirm 3D micro-CT can be used effectively for the non-invasive examination of the trabecular meshwork, Schlemm's canal, collector channels and intrascleral vasculature that comprise the distal outflow pathway. This imaging modality will be useful for non-invasive study of the role of the trabecular outflow pathway as a whole unit.

Relating function to branching geometry: a micro-CT study of the hepatic artery, portal vein, and biliary tree.

Utilizing micro-computed tomography images, the hierarchical structure, interbranch segment lengths and diameters of a hepatic artery, a portal vein, and two biliary trees from intact rat liver lobes were characterized. The data were investigated by analyzing the geometric properties of the vascular structures, such as how interbranch segment diameters change at bifurcation points. In the case of the hepatic artery and portal vein trees (in which the flow rate is high by comparison with that in the biliary tree), the vascular geometry is consistent with a fluid transport system which aims to simultaneously minimize both the power loss of laminar flow, and a cost function proportional to the total volume of material needed to maintain the system (lumenal contents). In comparison, the biliary tree (which has a low flow rate and an opposite flow direction to that of the hepatic artery and portal vein) was found to have a geometry in which the lumen cross-sectional area is maintained at bifurcations. These findings imply that the histological makeup and therefore the pathophysiology of biliary tree vasculature are likely very different from that of the vasculature within the systemic arterial tree. The extent to which the characteristic variability/scatter in the data may have resulted from imaging and/or measurement errors was examined by simulating such errors in a theoretical tree model and comparing the results with the measured data.

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.

Vascular metallomics: copper in the vasculature.

Owing to recent progress in analytical techniques, metallomics are evolving from detecting distinct trace metals in a defined state to monitor the dynamic changes in the abundance and location of trace metals in vitro and in vivo. Vascular metallomics is an emerging field that studies the role of trace metals in vasculature. This review will introduce common metallomics techniques including atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry with a summary table to compare these techniques. Moreover, we will summarize recent research findings that have applied these techniques to human population studies in cardiovascular diseases, with a particular emphasis on the role of copper in these diseases. In order to address the issue of interdisciplinary studies between metallomics and vascular biology, we will review the progress of efforts to understand the role of copper in neovascularization. This recent advance in the metallomics field may be a powerful tool to elucidate the signaling pathways and specific biological functions of these trace metals. Finally, we summarize the evidence to support the notion that copper is a dynamic signaling molecule. As a future direction, vascular metallomics studies may lead to the identification of targets for diagnosis and therapy in cardiovascular disease.

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 microm)(3). Contrast in the main lumen increased the CT values dramatically at voxels greater than (100 microm)(3), whereas CT values of the same specimen without contrast in the main lumen remained constant. CONCLUSIONS: Voxel sizes less than (200 microm)(3) are needed to quantitate arterial wall opacification due to vasa vasorum proliferation.

Overcoming calcium blooming and improving the quantification accuracy of percent area luminal stenosis by material decomposition of multi-energy computed tomography datasets.

Purpose: Conventional stenosis quantification from single-energy computed tomography (SECT) images relies on segmentation of lumen boundaries, which suffers from partial volume averaging and calcium blooming effects. We present and evaluate a method for quantifying percent area stenosis using multienergy CT (MECT) images. Approach: We utilize material decomposition of MECT images to measure stenosis based on the ratio of iodine mass between vessel locations with and without a stenosis, thereby eliminating the requirement for segmentation of iodinated lumen. The method was first assessed using simulated MECT images created with different spatial resolutions. To experimentally assess this method, four phantoms with different stenosis severity (30% to 51%), vessel diameters (5.5 to 14 mm), and calcification densities (700 to 1100 mgHA / cc ) were fabricated. Conventional SECT images were acquired using a commercial CT system and were analyzed with commercial software. MECT images were acquired using a commercial dual-energy CT (DECT) system and also from a research photon-counting detector CT (PCD-CT) system. Three-material-decomposition was performed on MECT data, and iodine density maps were used to quantify stenosis. Clinical radiation doses were used for all data acquisitions. Results: Computer simulation verified that this method reduced partial volume and blooming effects, resulting in consistent stenosis measurements. Phantom experiments showed accurate and reproducible stenosis measurements from MECT images. For DECT and two-threshold PCD-CT images, the estimation errors were 4.0% to 7.0%, 2.0% to 9.0%, 10.0% to 18.0%, and - 1.0 % to - 5.0 % (ground truth: 51%, 51%, 51%, and 30%). For four-threshold PCD-CT images, the errors were 1.0% to 3.0%, 4.0% to 6.0%, - 1.0 % to 9.0%, and 0.0% to 6.0%. Errors using SECT were much larger, ranging from 4.4% to 46%, and were especially worse in the presence of dense calcifications. Conclusions: The proposed approach was shown to be insensitive to acquisition parameters, demonstrating the potential to improve the accuracy and precision of stenosis measurements in clinical practice.

Role of computed tomography voxel size in detection and discrimination of calcium and iron deposits in atherosclerotic human coronary artery specimens.

OBJECTIVE: This study evaluated the influence of voxel size on its ability to discriminate calcium from iron deposits in ex vivo coronary arteries. METHODS: Postmortem human coronary arteries underwent multislice computed tomographic scan at (600-microm) voxel size to provide an index of computed tomography (CT) image noise and synchrotron-based micro-CT at (4-microm) voxel size to provide data for generating a range of voxel sizes 4 to (600-microm) after grayscale noise was added to the projection images before reconstruction so as to mimic the effect of retaining the same radiation exposure involved in the multislice computed tomographic scan. RESULTS: At voxel sizes of (20-microm) or smaller, iron deposits could be identified based on CT grayscale value. Voxels of (100-microm) or larger cannot resolve nor distinguish iron deposits from calcifications by virtue of CT grayscale value. CONCLUSIONS: Clinical CT scanners cannot be expected to discriminate iron deposits from calcifications by their CT value alone in the arterial wall.

Probing the Depth of the Myocardium: Vasculature, Transit Time, and Perfusion Within the Left Ventricular Wall.

The branching architecture of arterial trees traversing the thickness of the left ventricular wall is studied to determine the way in which adequate blood supply is provided to myocardial tissue at different depths within the wall thickness from arterial trees originating at the epicardial surface. The study is based on micro-CT images of tissue biopsies, coupled with a dedicated vascular tree analysis program. The results show that this combination of methodologies allows a more detailed and much more accurate exploration of the vasculature within the sampled tissue than is possible by histological means. The spatial density of the smallest resolvable "end" arterioles is found to be higher in the sub-endocardial region than in the sub-epicardial region, with vascular branching architecture consistent with a fractal structure. The concept of "transit time" is introduced as an approximate measure of the time it takes bulk flow to reach different regions of the myocardium. Our data suggest that a transit time differential is a major contributor to the equalization of transmural perfusion gradient against unequal distribution of "end' arteriolar density.

Impact of Effective Detector Pixel and CT Voxel Size on Accurate Estimation of Blood Volume in Opacified Microvasculature.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the impact of effective detector-pixel-size and image voxel size on the accurate estimation of microvessel density (ratio of microvascular lumen volume/tissue volume) in an excised porcine myocardium specimen using microcomputed tomography (CT), and the ability of whole-body energy-integrating-detector (EID) CT and photon-counting-detector (PCD) CT to measure microvessel density in the same ex vivo specimen. MATERIALS AND METHODS: Porcine myocardial tissue in which the microvessels contained radio-opaque material was scanned using a micro-CT scanner and data were generated with a range of detector pixel sizes and image voxel sizes from 20 to 260 microns, to determine the impact of these parameters on the accuracy of microvessel density estimates. The same specimen was scanned in a whole-body EID CT and PCD CT system and images reconstructed with 600 and 250 micron slice thicknesses, respectively. Fraction of tissue volume that is filled with opacified microvessels was determined by first subtracting the mean background attenuation value from all voxels, and then by summing the remaining attenuation. RESULTS: Microvessel density data were normalized to the value measured at 20 µm voxel size, which was considered reference truth for this study. For emulated micro-CT voxels up to 260 µm, the microvessel density was underestimated by at most 11%. For whole-body EID CT and PCD CT, microvessel density was underestimated by 9.5% and overestimated by 0.1%, respectively. CONCLUSION: Our data indicate that microvessel density can be accurately calculated from the larger detector pixels used in clinical CT scanners by measuring the increase of CT attenuation caused by these opacified microvessels.