Evaluation of neural innervation in the human conventional outflow pathway distal to Schlemm's canal.

The distal outflow pathway of the human eye consists of the outer wall of Schlemm's canal, collector channels, and the deep-scleral, mid-scleral and episcleral vessels. It is the last region of transit for aqueous humor before returning to the venous system. While the trabecular meshwork, scleral spur, and inner wall of Schlemm's canal have been extensively analyzed to define their contributions to aqueous outflow, the role of the distal outflow pathway is not completely understood. Collector channels, emanating from Schlemm's canal were previously thought to be passive conduits for aqueous humor. However, recent studies have shown many collector channels contain flap-like appendages which move with changes in pressure. These findings, along with studies demonstrating innervation of episcleral vessels, have led to questions regarding whether other structures in the distal outflow pathway are under neural regulation and how this may influence aqueous humor outflow. This study evaluates the innervation of the outer wall of Schlemm's canal and collector channels, along with the deep-scleral, mid-scleral and episcleral vasculature with microcomputed tomography and 3-dimensional reconstruction, correlative light microscopy, immunohistochemistry, and transmission electron microscopy. Peripheral, autonomic, and sensory nerve fibers were found to be present adjacent to Schlemm's canal outer wall endothelium, collector channel endothelium, and in the different regions of the distal outflow vasculature. Nerves were more commonly identified in regions that contained collector channels when compared to regions without collector channels. These findings regarding the neural anatomy suggest an active neural regulation of aqueous humor outflow throughout the proximal and distal regions of the conventional outflow pathway.

Semantic Instance Segmentation of Kidney Cysts in MR Images: A Fully Automated 3D Approach Developed Through Active Learning.

Total kidney volume (TKV) is the main imaging biomarker used to monitor disease progression and to classify patients affected by autosomal dominant polycystic kidney disease (ADPKD) for clinical trials. However, patients with similar TKVs may have drastically different cystic presentations and phenotypes. In an effort to quantify these cystic differences, we developed the first 3D semantic instance cyst segmentation algorithm for kidneys in MR images. We have reformulated both the object detection/localization task and the instance-based segmentation task into a semantic segmentation task. This allowed us to solve this unique imaging problem efficiently, even for patients with thousands of cysts. To do this, a convolutional neural network (CNN) was trained to learn cyst edges and cyst cores. Images were converted from instance cyst segmentations to semantic edge-core segmentations by applying a 3D erosion morphology operator to up-sampled versions of the images. The reduced cysts were labeled as core; the eroded areas were dilated in 2D and labeled as edge. The network was trained on 30 MR images and validated on 10 MR images using a fourfold cross-validation procedure. The final ensemble model was tested on 20 MR images not seen during the initial training/validation. The results from the test set were compared to segmentations from two readers. The presented model achieved an averaged R2 value of 0.94 for cyst count, 1.00 for total cyst volume, 0.94 for cystic index, and an averaged Dice coefficient of 0.85. These results demonstrate the feasibility of performing cyst segmentations automatically in ADPKD patients.

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).

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 Prediction of Kidney Stone Fragility Using Radiomics-Based Regression Models.

Introduction: The surgical technique for urinary stone removal is partly influenced by its fragility, as prognosticated by the clinician. This feasibility study aims to develop a linear regression model from CT-based radiomic markers to predict kidney stone comminution time in vivo with two ultrasonic lithotrites. Materials and Methods: Patients identified by urologists at our institution as eligible candidates for percutaneous nephrolithotomy were prospectively enrolled. The active engagement time of the lithotrite in breaking the stone during surgery denoted the comminution time of each stone. The comminution rate was computed as the stone volume disintegrated per minute. Stones were grouped into three fragility classes (fragile, moderate, hard), based on inverse of the comminution rates with respect to the mean. Multivariable linear regression models were trained with radiomic features extracted from clinical CT images to predict comminution times in vivo. The model with the least root mean squared error (RMSE) on comminution times and the fewest misclassification of fragility was finally selected. Results: Twenty-eight patients with 31 stones in total were included in this study. Stones in the cohort averaged 1557 (±2472) mm3 in volume and 5.3 (±7.4) minutes in comminution time. Ten stones had nonmoderate fragility. Linear regression of stone volume alone predicted comminution time with an RMSE of 6.8 minutes and missed all 10 stones with nonmoderate fragility. A fragility model that included stone volume, internal morphology, shape-based radiomics, and device type improved RMSE to below 3.3 minutes and correctly classified 20/21 moderate and 6/10 nonmoderate stones. Conclusions: CT metrics-based fragility models may provide information to surgeons regarding kidney stone fragility and facilitate the selection of stone removal procedures.

Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters.

OBJECTIVE: Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS: BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS: The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS: The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

A training program to reduce reader search errors for liver metastasis detection in CT.

Detection of low contrast liver metastases varies between radiologists. Training may improve performance for lower-performing readers and reduce inter-radiologist variability. We recruited 31 radiologists (15 trainees, 8 non-abdominal staff, and 8 abdominal staff) to participate in four separate reading sessions: pre-test, search training, classification training, and post-test. In the pre-test, each radiologist interpreted 40 liver CT exams containing 91 metastases, circumscribed suspected hepatic metastases while under eye tracker observation, and rated confidence. In search training, radiologists interpreted a separate set of 30 liver CT exams while receiving eye tracker feedback and after coaching to increase use of coronal reformations, interpretation time, and use of liver windows. In classification training, radiologists interpreted up to 100 liver CT image patches, most with benign or malignant lesions, and compared their annotations to ground truth. Post-test was identical to pre-test. Between pre- and post-test, sensitivity increased by 2.8% (p = 0.01) but AUC did not change significantly. Missed metastases were classified as search errors (<2 seconds gaze time) or classification errors (>2 seconds gaze time) using the eye tracker. Out of 2775 possible detections, search errors decreased (10.8% to 8.1%; p < 0.01) but classification errors were unchanged (5.7% vs 5.7%). When stratified by difficulty, easier metastases showed larger reductions in search errors: for metastases with average sensitivity of 0-50%, 50-90%, and 90-100%, reductions in search errors were 16%, 35%, and 58%, respectively. The training program studied here may be able to improve radiologist performance by reducing errors but not classification errors.

Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis.

UNLABELLED: Paracrine signaling between hepatic stellate cells (HSCs) and liver endothelial cells (LECs) modulates fibrogenesis, angiogenesis, and portal hypertension. However, mechanisms regulating these processes are not fully defined. Sorafenib is a receptor tyrosine kinase inhibitor that blocks growth factor signaling in tumor cells but also displays important and not yet fully characterized effects on liver nonparenchymal cells including HSCs and LECs. The aim of this study was to test the hypothesis that sorafenib influences paracrine signaling between HSCs and LECs and thereby regulates matrix and vascular changes associated with chronic liver injury. Complementary magnetic resonance elastography, micro-computed tomography, and histochemical analyses indicate that sorafenib attenuates the changes in both matrix and vascular compartments that occur in response to bile duct ligation-induced liver injury in rats. Cell biology studies demonstrate that sorafenib markedly reduces cell-cell apposition and junctional complexes, thus reducing the proximity typically observed between these sinusoidal barrier cells. At the molecular level, sorafenib down-regulates angiopoietin-1 and fibronectin, both released by HSCs in a manner dependent on the transcription factor Kruppel-like factor 6 , suggesting that this pathway underlies both matrix and vascular changes associated with chronic liver disease. CONCLUSION: Collectively, the results of this study demonstrate that sorafenib inhibits both matrix restructuring and vascular remodeling that accompany chronic liver diseases and characterize cell and molecular mechanisms underlying this effect. These data may help to refine future therapies for advanced gastrointestinal and liver diseases characterized by abundant fibrosis and neovascularization.

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.

Magnetic resonance radiomic feature performance in pulmonary nodule classification and impact of segmentation variability on radiomics.

OBJECTIVE: Investigate the performance of multiparametric MRI radiomic features, alone or combined with current standard-of-care methods, for pulmonary nodule classification. Assess the impact of segmentation variability on feature reproducibility and reliability. METHODS: Radiomic features were extracted from 74 pulmonary nodules of 68 patients who underwent nodule resection or biopsy after MRI exam. The MRI features were compared with histopathology and conventional quantitative imaging values (maximum standardized uptake value [SUVmax] and mean Hounsfield unit [HU]) to determine whether MRI radiomic features can differentiate types of nodules and associate with SUVmax and HU using Wilcoxon rank sum test and linear regression. Diagnostic performance of features and four machine learning (ML) models were evaluated with area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs). Concordance correlation coefficient (CCC) assessed the segmentation variation impact on feature reproducibility and reliability. RESULTS: Elevn diffusion-weighted features distinguished malignant from benign nodules (adjusted p < 0.05, AUC: 0.73-0.81). No features differentiated cancer types. Sixty-seven multiparametric features associated with mean CT HU and 14 correlated with SUVmax. All significant MRI features outperformed traditional imaging parameters (SUVmax, mean HU, apparent diffusion coefficient [ADC], T1, T2, dynamic contrast-enhanced imaging values) in distinguishing malignant from benign nodules with some achieving statistical significance (p < 0.05). Adding ADC and smoking history improved feature performance. Machine learning models demonstrated strong performance in nodule classification, with extreme gradient boosting (XGBoost) having the highest discrimination (AUC = 0.83, CI=[0.727, 0.932]). We found good to excellent inter- and intrareader feature reproducibility and reliability (CCC≥0.80). CONCLUSION: Eleven MRI radiomic features differentiated malignant from benign lung nodules, outperforming traditional quantitative methods. MRI radiomic ML models demonstrated good nodule classification performances with XGBoost superior to three others. There was good to excellent inter- and intrareader feature reproducibility and reliability. ADVANCES IN KNOWLEDGE: Our study identified MRI radiomic features that successfully differentiated malignant from benign lung nodules and demonstrated high performance of our MR radiomic feature-based ML models for nodule classification. These new findings could help further establish thoracic MRI as a non-invasive and radiation-free alternative to standard practice for pulmonary nodule assessment.

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.

Preconditioning with Foam-mediated External Suction on Flap Microvasculature and Perfusion in a Rodent Model.

Foam-mediated external suction (FMES) has previously shown to improve tissue microcirculation. We hypothesized that preconditioning fasciocutaneous perforator flaps with FMES would augment perfusion and demonstrate greater capillary recruitment. METHODS: Gluteal perforator flaps were designed on sixteen 400 g rats. Continuous FMES at -125 mm Hg was applied on one side (intervention) to precondition tissue for 5 days, with the contralateral side as a paired control. In group A, we assessed changes following pretreatment, after surgery, and 7 days postprocedure, and in group B, we evaluated changes during preconditioning alone. In group A (N = 8), control and intervention flaps were assessed using laser-assisted indocyanine green fluorescence angiography. In group B, flap regions were assessed using 4-dimensional computed tomographic angiography. All flaps were analyzed for microvessel density using micro-computed tomography and histological assessment using hematoxylin and eosin and CD3 immunohistochemistry. RESULTS: Thirty-two flaps were included in this study (N = 16 intervention and matched controls). Four-dimensional computed tomographic angiography demonstrated 17% greater tissue perfusion in preconditioned flaps (mean, 78.7 HU; SD, 8.8) versus controls (mean, 67.3 HU; SD, 15.7; P < 0.01). Laser-assisted indocyanine green fluorescence angiography showed a 30% higher mean absolute intensity in preconditioned flaps versus controls (P < 0.01). Postsurgery mean absolute intensity in preconditioned flaps remained 21% higher than in controls (P = 0.03). Preconditioned flaps demonstrated a 2-fold increase in mean vessel volume of 9.1 mm3 (SD, 7) versus 4.5 mm3 (SD, 3) in controls (P = 0.04); there was a 33% higher mean area fraction of CD31 in preconditioned flaps, 3.9% (SD, 3) versus 2.9% (SD, 3) in controls (P = 0.03). CONCLUSION: FMES preconditioning has the potential to augment vascularity of tissue for flap harvest; however, further experimental studies are required to optimize strategies and evaluate long-term effects for clinical applications.

A Blooming correction technique for improved vasa vasorum detection using an ultra-high-resolution photon-counting detector CT.

Proliferation of vasa vasorum, the microvasculature within artery walls, is an early marker of atherosclerosis. Detection of subtle changes in the spatial density of vasa vasorum using contrast-enhanced CT is challenging due to the limited spatial resolution and blooming effects. We report a forward model-based blooming correction technique to improve vasa vasorum detection in a porcine model imaged using an ultra-high resolution photon-counting detector CT. Six weeks preceding the CT study the animal received autologous blood injections in its left carotid artery to stimulate vasa vasorum proliferation within the arterial wall (right carotid served as control). The forward model predicted radial extent and magnitude of the luminal blooming affecting the wall signal by using prior data acquired with a vessel phantom of known dimensions. The predicted contamination from blooming was then subtracted from the original wall signal measurement to recover the obscured vasa vasorum signal. Attenuation measurements made on a testing vessel phantom before and after blooming corrections revealed a reduction in mean squared error by ~99.9% when compared to the ground truth. Applying corrections to contrast-enhanced carotid arteries from in vivo scan data demonstrated consistent reductions of blooming contamination within the vessel walls. An unpaired student t-test applied to measurements from the uncorrected porcine scan data revealed no significant difference between the vessel walls (p=0.26). However, after employing blooming correction, the mean enhancement was significantly greater in the injured vessel wall (p=0.0006).

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.

Evaluation of a photon counting Medipix3RX cadmium zinc telluride spectral x-ray detector.

We assess the performance of a cadmium zinc telluride (CZT)-based Medipix3RX energy-resolving and photon-counting x-ray detector as a candidate for spectral microcomputed tomography (micro-CT) imaging. It features an array of 128 × 128 , 110 - µ m 2 pixels, each with four simultaneous threshold counters that utilize real-time charge summing. Each pixel's response is assessed by imaging with a range of incident x-ray intensities and detector integration times. Energy-related assessments are made by exposing the detector to the emission from an I-125 radioisotope brachytherapy seed. Long-term stability is assessed by repeating identical exposures over the course of 1 h. The high yield of properly functioning pixels (98.8%), long-term stability (linear regression of whole-chip response over 1 h of acquisitions: y = - 0.0038 x + 2284 ; standard deviation: 3.7 counts), and energy resolution [2.5 keV full-width half-maximum (FWHM) (single pixel), 3.7 keV FWHM (across the full image)] make this device suitable for spectral micro-CT.

A Three-Dimensional Micro-Computed Tomographic Study of the Intraosseous Lunate Vasculature: Implications for Surgical Intervention and the Development of Avascular Necrosis.

BACKGROUND: The purpose of this study was to use micro-computed tomography to demonstrate the intraosseous vascularity of the lunate within a three-dimensional orientation to identify areas of greatest perfusion and define vascular "safe zones" for surgical intervention. METHODS: Fourteen upper extremities were injected with a lead-based contrast agent. The lunates were harvested and scanned using a micro-computed tomography scanner. The intraosseous vascularity was incorporated into a three-dimensional image. Vessel number, diameter, distribution, and pattern were evaluated and analyzed. Vascularity of all specimens was projected onto one representative lunate to identity areas of higher and lower vascularity. RESULTS: Twelve specimens had nutrient vessels entering the bone from volar and dorsal; two specimens had no dorsal vessels. The intraosseous vascularity could be classified according to the Y, I, and X patterns described by Gelberman et al. Average number and diameter of vessels were 2.3 and 118.1 µm, respectively, for volar; and 1.4 and 135.8 µm, respectively, for dorsal. The long axis of the lunate showed the highest vascularity on both axial and lateral views. Lower vascularity was observed in the dorsoradial and volar-ulnar quadrants on the axial view, and in the proximal part on the lateral view. Lunate shape was not associated with an increase or decrease in nutrient vessels or vascular pattern. CONCLUSIONS: Vascular safe zones were identified, allowing for potentially safer surgical interventions to the lunate. Volar approaches to the lunate may result in localized ischemia in a subset of patients with absent dorsal nutrient vessels. This study may help to better define patients at risk for Kienböck disease.

Evaluation of a photon counting Medipix3RX CZT spectral x-ray detector.

We assessed the performance of a cadmium zinc telluride (CZT)-based Medipix3RX x-ray detector as a candidate for micro-computed tomography (micro-CT) imaging. This technology was developed at CERN for the Large Hadron Collider. It features an array of 128 by 128, 110 micrometer square pixels, each with eight simultaneous threshold counters, five of which utilize real-time charge summing, significantly reducing the charge sharing between contiguous pixels. Pixel response curves were created by imaging a range of x-ray intensities by varying x-ray tube current and by varying the exposure time with fixed x-ray current. Photon energy-related assessments were made by flooding the detector with the tin foil filtered emission of an I-125 radioisotope brachytherapy seed and sweeping the energy threshold of each of the four charge-summed counters of each pixel in 1 keV steps. Long term stability assessments were made by repeating exposures over the course of one hour. The high properly-functioning pixel yield (99%), long term stability (linear regression of whole-chip response over one hour of acquisitions: y = -0.0038x + 2284; standard deviation: 3.7 counts) and energy resolution (2.5 keV FWHM (single pixel), 3.7 keV FWHM across the full image) make this device suitable for spectral micro-CT. The charge summing performance effectively reduced the measurement corruption caused by charge sharing which, when unaccounted for, shifts the photon energy assignment to lower energies, degrading both count and energy accuracy. Effective charge summing greatly improves the potential for calibrated, energy-specific material decomposition and K edge difference imaging approaches.

Arterial Wall Perfusion Measured with Photon Counting Spectral X-ray CT.

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 × 0.16 × 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.

Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

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.