Erik L. Ritman

PurposeThe 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.ApproachVasa 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.ResultsThe 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.ConclusionsWhole-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.

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.

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.

Early atherosclerosis changes perfusion of the arterial wall due to localized proliferation of the vasa vasorum. When contrast agent passes through the artery, some enters the vasa vasorum and increases radiopacity of the arterial wall. Technical challenges to detecting changes in vasa vasorum density include the thin arterial wall, partial volume averaging at the arterial lumen/wall interface and calcification within the wall. We used a photon-counting spectral CT scanner to study carotid arteries of anesthetized pigs and micro-CT of these arteries to quantify vasa vasorum density. The left carotid artery wall was injected with autologous blood to stimulate vasa vasorum angiogenesis. The scans were performed at 25-120 keV; the tube-current-time product was 550 mAs. A 60 mL bolus of iodine contrast agent was injected into the femoral vein at 5mL/s. Two seconds post injection, an axial scan was acquired at every 3 s over 60 s (i.e., 20 time points). Each time point acquired 28 contiguous transaxial slices with reconstructed voxels 0.16 x 0.16 x 1 mm3. Regions-of-interest in the outer 2/3 of the arterial wall and in the middle 2/3 of the lumen were drawn and their enhancements plotted versus time. Lumenal CT values peaked several seconds after injection and then returned towards baseline. Arterial wall CT values peaked concurrent to the lumen. The peak arterial wall enhancement in the left carotid arterial wall correlated with increased vasa vasorum density observed in micro-CT images of the isolated arteries.

A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 μm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control.

Intramyocardial microvessels demonstrate functional changes in cardiomyopathies. However, clinical computed tomography (CT) does not have adequate spatial resolution to assess the microvessels. Our hypothesis is that these functional changes manifest as altered heterogeneity of the spatial distribution of arteriolar perfusion territories. Our goal was to determine whether the spatial analysis of perfusion CT could clinically detect changes in the function and structure of the intramyocardial microcirculation in a non-ischemic dilated cardiomyopathy (DCM). Two groups were studied: (1) a Control group (12 male plus 12 female) with no risk factors nor evidence of coronary artery disease, and (2) a DCM group (12 male plus 12 female) with left ventricular ejection fraction ≤40 % and no evidence of coronary artery disease. Using the CT scan, the LV free wall thickness and its radius of curvature were measured. The DCM group was sub divided into those with LV free wall thickness <11.5 mm and those with thickness ≥11.5 mm. In the myocardial opacification phase of the CT scan sequence, myocardial perfusion (F) and intramyocardial blood volume (Bv) for multiple intramyocardial regions were computed. No significant differences between the groups were demonstrable in overall myocardial F or Bv. However, the myocardial regional data showed significantly increased spatial heterogeneity in the DCM group when compared to the Control group. The findings demonstrate that altered function of the subresolution intramyocardial microcirculation can be quantified with myocardial perfusion CT and that significant changes in these parameters occur in the DCM subjects with LV wall thickness greater than 11.5 mm.

During World War 2, Earl Wood was charged with elucidating the biomedical factors in acceleration-induced loss of consciousness experienced by pilots in high-performance aircraft. For this, he developed devices for measurement and recording of blood pressure and tissue blood content. Those data lead to the design and fabrication of successful countermeasures to acceleration-induced loss of consciousness with an inflatable “G-suit” and “M1” breath-holding maneuver. After World War 2, he utilized and modified these instruments and made use of indicator dilution techniques by continuous intracardiac blood sampling to greatly increase the specificity and sensitivity of diagnosis of intracardiac anatomic and functional abnormalities in patients with congenital heart disease. This contributed to the greatly increased success rate of open-heart surgery in the 1950s. In the 1960s, he built on the then recently available video-coupled electronic X-ray image intensifier to develop X-ray fluoroscopy-based recording of indicator dilution signals in all cardiac chambers and surrounding great vessels without the need for placing catheter tips at those locations for blood sampling. However, these blood flow-related data were of limited value, as they were not measured concurrent with myocardial functional demand for perfusion. In the 1970s, he overcame this limitation by developing a high-speed multislice X-ray imaging scanner to provide tomographic images of concurrent dynamic cardiac anatomy and the indicator dilution-based estimates of blood flow distributions. On his retirement at age 70 in 1982, he had accomplished his 2 decade-old goal of the ability to make accurate concurrent, minimally invasive, and indicator dilution-based measurement of cardiovascular structure to function relationships.

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).