Ultrastructural Study of Platelet Behavior and Interrelationship in Sprouting and Intussusceptive Angiogenesis during Arterial Intimal Thickening Formation

Platelets in atherosclerosis, bypass stenosis, and restenosis have been extensively assessed. However, a sequential ultrastructural study of platelets in angiogenesis during the early phases of these lesions has received less attention. Our objective was the study of platelets in angiogenesis and vessel regression during intimal thickening (IT) formation, a precursor process of these occlusive vascular diseases. For this purpose, we used an experimental model of rat occluded arteries and procedures for ultrastructural observation. The results show (a) the absence of platelet adhesion in the de-endothelialized occluded arterial segment isolated from the circulation, (b) that intraarterial myriad platelets contributed from neovessels originated by sprouting angiogenesis from the periarterial microvasculature, (c) the association of platelets with blood components (fibrin, neutrophils, macrophages, and eosinophils) and non-polarized endothelial cells (ECs) forming aggregates (spheroids) in the arterial lumen, (d) the establishment of peg-and-socket junctions between platelets and polarized Ecs during intussusceptive angiogenesis originated from the EC aggregates, with the initial formation of IT, and (e) the aggregation of platelets in regressing neovessels (‘transitory paracrine organoid’) and IT increases. In conclusion, in sprouting and intussusceptive angiogenesis and vessel regression during IT formation, we contribute sequential ultrastructural findings on platelet behavior and relationships, which can be the basis for further studies using other procedures.

Abstract 16747: Rapidly Lethal Dilated Cardiomyopathy Secondary To Generalized Arterial Calcification Of Infancy

Case Presentation: A previously healthy 3-month-old infant presented with cardiorespiratory arrest, from which she was successfully resuscitated. A dilated cardiomyopathy with severely depressed systolic function was diagnosed. ECG showed high voltage QRS complexes and generalized alteration of repolarization. In the following 12 hours, she suffered 2 other cardiac arrests, recuperated with defibrillation. Hemodinamic stability was achieved but brain death was diagnosed 36 hours after the onset of symptoms. Autopsy showed striking calcification of the right and left coronary arteries, with narrowing of the arterial lumen, causing extensive subendocardial infarction. Calcification also affected the aorta, pulmonary arteries, thyroid, kidney and other splanchnic arteries. Generalized arterial calcification of infancy (GACI) was diagnosed and a genetic study found two biallelic variants in ABCC6 gene: p.Arg1114Cys and p.Trp38Ser, both previously described in elastic pseudoxanthoma (PXE), but not in GACI. Genotyping of the healthy parents confirmed genetic segregation with biallelic variants. Discussion: GACI is an extremely rare genetic disease characterized by widespread arterial calcification and narrowing of large and medium-sized vessels. The usual clinical presentation is heart failure in fetal life or in the first months of infancy. In most cases it is lethal, with death occurring within a few hours or days after the onset of symptoms, although clinical involvement is highly variable and cases with long survival have been described. GACI is an autosomal recessive disease secondary to biallelic variants in the ENPP1 gene (67% of cases) and in the ABCC6 gene (9%). The variants found in our patient had not been previously described in GACI, just in PXE, a much milder disease with usually normal lifespan. This case confirms that both entities reflect two extremes of a clinical spectrum of ectopic calcification instead of two different disorders. The aim of presenting this case is to remind clinicians of this rare etiology in neonates or infants with dilated cardiomyopathy. In case of death, autopsy should always be requested. When this condition is diagnosed, genetic study will be positive in 75% of cases, allowing prenatal counseling.

Acute hemodialysis catheter follows the path of least resistance

The placement of large bore double-lumen catheters for hemodialysis (HD) is one of the most frequent procedures performed in HD patients. However, these procedures are associated with complications, the most common being catheter malposition. In this context, catheter deviation to the left superior intercostal vein (LISV) is a very uncommon malposition, which must be differentiated from intrathoracic extravascular catheter lodgment. We report a case of an adult male patient on hemodialysis who presented with a thrombosed arteriovenous fistula and requiring urgent HD. His past medical history included hemophilia, allergy to contrast media, and multiple previous central vein catheterizations. A non-tunneled HD catheter was placed without any difficulty in the left internal jugular vein. However, the arterial lumen failed to pull any blood with free flow in the venous lumen. A chest X-ray revealed a surprising finding. The malpositioned catheter was removed successfully without any complications.

Systemic mucoid degeneration of the arterial tunica intima in a young dog

A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue–positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α–smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.

Towards a better understanding of the posttreatment hemodynamic behaviors in femoropopliteal arteries through personalized computational models based on OCT images

The hemodynamic behavior following endovascular treatment of patients with peripheral arterial disease plays a significant role on the occurrence of restenosis in femoro-popliteal (FP) arteries. The atheroprone flow conditions that are generally accepted to promote restenosis can be calculated by computational fluid dynamics (CFD) analyses, and these results can be used to assess individualized treatment outcomes. However, the impact of endovascular therapy on the flow behaviors of FP arteries are still poorly understood, as the imaging modalities used in existing numerical works (X-ray angiography, computed tomography angiography) are unable to accurately represent the post-treatment arterial geometry due to their low resolutions. Therefore, this study proposes a new algorithm that combines intra-arterial lumen geometry obtained from high-resolution optical coherence tomography (OCT) images with centerlines generated from X-ray images to reconstruct the FP artery with an in-plane resolution of 10 µm. This superior accuracy allows modeling characteristic geometrical structures, such as angioplasty-induced arterial dissections, that are too small to be reconstructed with other imaging modalities. The framework is applied on the clinical data of patients treated either with only-percutaneous transluminal angioplasty (PTA) (n = 4) or PTA followed by stenting (n = 4). Based on the generated models, PTA was found to cause numerous arterial dissections, covering approximately 10% of the total surface area of the lumen, whereas no dissections were identified in the stented arteries. CFD simulations were performed to investigate the hemodynamic conditions before and after treatment. Regardless of the treatment method, the areas affected by low time-averaged wall shear stress (< 0.5 Pa) were significantly higher (p < 0.05) following endovascular therapy (pre-PTA: 0.95 ± 0.59 cm2; post-PTA: 2.10 ± 1.09cm2; post-stent: 3.10 ± 0.98 cm2). There were no statistical differences between the PTA and the stent groups. However, within the PTA group, adverse hemodynamics were mainly concentrated at regions created by arterial dissections, which may negatively impact the outcomes of a leave-nothing-behind strategy. These observations show that OCT-based numerical models have great potential to guide clinicians regarding the optimal treatment approach.

Effect of the ratio of vessel-specific volume to fractional myocardial mass on fractional flow reserve

This study aimed to examine whether the ratio of vessel-specific coronary arterial lumen volume to the fraction of myocardial mass (VR/MR) affects myocardial ischemia. We proposed a calculation method for VR/MR, and compared the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) with VR/MR in predicting myocardial ischemia. VR/MR and V/M were computed using data from 205 patients with 241 stenosis vessel who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography, and fractional flow reserve. The vessel-specific coronary arterial lumen volume (VR) was obtained from CTA by segmenting the coronary arterial lumen volume, while the vessel-specific fraction of myocardial mass (MR) was obtained by allometric scaling. The VR/MR was then calculated. The cut-off values of V/M (23.55 mm3/g) and VR/MR (12.98 mm3/g) were used to define equal groups of ischemic and non-ischemic patients, respectively. Using these cut-off values, the accuracy, specificity, sensitivity, positive predictive value, and negative predictive value of V/M were 60%, 76%, 45%, 57%, and 66%, and of VR/MR were 87%, 92%, 77%, 89%, and 83%, respectively. Patients have different VR/MR values in different stenotic coronary arteries. Clinically, VR/MR is a quantitative indicator of the risk of myocardial ischemia.

Development of an Intravascular Doppler Optical Coherence Tomography Imaging Technique for Neurovascular Applications

The rupture of an intracranial aneurysm can cause spontaneous subarachnoid hemorrhage and result in sudden death. A large portion of intracranial aneurysms occurs near the center of the head, at the skull base, which poses significant technical challenge to neurosurgeons due to limited accessibility. The utilization of angiography is prominent during the treatment of intracranial aneurysms. However, malapposition of stent or incomplete packing of the intracranial aneurysm can be difficult to assess with angiography, and could lead to severe postoperative complications. As a result, angiography may not be sufficient in determining the risk of rupture as the compensatory mechanisms are known to occur at the microstructural level due to the local hemodynamics in the arterial lumen, as well as in evaluating the intraoperative treatment. In this work, we describe a method for assessing intracranial aneurysm through the evaluation of blood flow within the lumen and morphological structures of the arterial wall with optical coherence tomography (OCT). Sterile intravascular fiber-optic catheters can be introduced in the artery to detect blood flow. Prior to this work, limited investigations of catheter based Doppler OCT (DOCT) were reported. A novel signal processing technique was developed to further reduce the effect of Doppler noise within a catheter based DOCT system. This technique consisted of splitting the interferogram of an OCT signal prior to estimating the Doppler shift. This split spectrum DOCT (ssDOCT) method was evaluated through flow models and porcine models, as well as through the correlation between ssDOCT algorithm and computational fluid dynamic (CFD) models. It was observed that ssDOCT provided improved Doppler artefact suppression over the conventional DOCT technique. ssDOCT also provided the ability to estimate lower velocities within the DOCT image to measure the hemodynamic patterns around stent struts in both the internal carotid and patient specific flow phantoms. An OCT imaging study was also conducted consisting of surgically resected human intracranial aneurysms. Further enhancement of the detection of these key morphological structures was demonstrated by an optical-attenuation imaging variant of OCT. The presented techniques could provide further insights to the cause of intracranial aneurysm rupture and vascular healing mechanisms.

Development of an Intravascular Doppler Optical Coherence Tomography Imaging Technique for Neurovascular Applications

The rupture of an intracranial aneurysm can cause spontaneous subarachnoid hemorrhage and result in sudden death. A large portion of intracranial aneurysms occurs near the center of the head, at the skull base, which poses significant technical challenge to neurosurgeons due to limited accessibility. The utilization of angiography is prominent during the treatment of intracranial aneurysms. However, malapposition of stent or incomplete packing of the intracranial aneurysm can be difficult to assess with angiography, and could lead to severe postoperative complications. As a result, angiography may not be sufficient in determining the risk of rupture as the compensatory mechanisms are known to occur at the microstructural level due to the local hemodynamics in the arterial lumen, as well as in evaluating the intraoperative treatment. In this work, we describe a method for assessing intracranial aneurysm through the evaluation of blood flow within the lumen and morphological structures of the arterial wall with optical coherence tomography (OCT). Sterile intravascular fiber-optic catheters can be introduced in the artery to detect blood flow. Prior to this work, limited investigations of catheter based Doppler OCT (DOCT) were reported. A novel signal processing technique was developed to further reduce the effect of Doppler noise within a catheter based DOCT system. This technique consisted of splitting the interferogram of an OCT signal prior to estimating the Doppler shift. This split spectrum DOCT (ssDOCT) method was evaluated through flow models and porcine models, as well as through the correlation between ssDOCT algorithm and computational fluid dynamic (CFD) models. It was observed that ssDOCT provided improved Doppler artefact suppression over the conventional DOCT technique. ssDOCT also provided the ability to estimate lower velocities within the DOCT image to measure the hemodynamic patterns around stent struts in both the internal carotid and patient specific flow phantoms. An OCT imaging study was also conducted consisting of surgically resected human intracranial aneurysms. Further enhancement of the detection of these key morphological structures was demonstrated by an optical-attenuation imaging variant of OCT. The presented techniques could provide further insights to the cause of intracranial aneurysm rupture and vascular healing mechanisms.

Development of an Intravascular Doppler Optical Coherence Tomography Imaging Technique for Neurovascular Applications

The rupture of an intracranial aneurysm can cause spontaneous subarachnoid hemorrhage and result in sudden death. A large portion of intracranial aneurysms occurs near the center of the head, at the skull base, which poses significant technical challenge to neurosurgeons due to limited accessibility. The utilization of angiography is prominent during the treatment of intracranial aneurysms. However, malapposition of stent or incomplete packing of the intracranial aneurysm can be difficult to assess with angiography, and could lead to severe postoperative complications. As a result, angiography may not be sufficient in determining the risk of rupture as the compensatory mechanisms are known to occur at the microstructural level due to the local hemodynamics in the arterial lumen, as well as in evaluating the intraoperative treatment. In this work, we describe a method for assessing intracranial aneurysm through the evaluation of blood flow within the lumen and morphological structures of the arterial wall with optical coherence tomography (OCT). Sterile intravascular fiber-optic catheters can be introduced in the artery to detect blood flow. Prior to this work, limited investigations of catheter based Doppler OCT (DOCT) were reported. A novel signal processing technique was developed to further reduce the effect of Doppler noise within a catheter based DOCT system. This technique consisted of splitting the interferogram of an OCT signal prior to estimating the Doppler shift. This split spectrum DOCT (ssDOCT) method was evaluated through flow models and porcine models, as well as through the correlation between ssDOCT algorithm and computational fluid dynamic (CFD) models. It was observed that ssDOCT provided improved Doppler artefact suppression over the conventional DOCT technique. ssDOCT also provided the ability to estimate lower velocities within the DOCT image to measure the hemodynamic patterns around stent struts in both the internal carotid and patient specific flow phantoms. An OCT imaging study was also conducted consisting of surgically resected human intracranial aneurysms. Further enhancement of the detection of these key morphological structures was demonstrated by an optical-attenuation imaging variant of OCT. The presented techniques could provide further insights to the cause of intracranial aneurysm rupture and vascular healing mechanisms.

Development of an Intravascular Doppler Optical Coherence Tomography Imaging Technique for Neurovascular Applications

The rupture of an intracranial aneurysm can cause spontaneous subarachnoid hemorrhage and result in sudden death. A large portion of intracranial aneurysms occurs near the center of the head, at the skull base, which poses significant technical challenge to neurosurgeons due to limited accessibility. The utilization of angiography is prominent during the treatment of intracranial aneurysms. However, malapposition of stent or incomplete packing of the intracranial aneurysm can be difficult to assess with angiography, and could lead to severe postoperative complications. As a result, angiography may not be sufficient in determining the risk of rupture as the compensatory mechanisms are known to occur at the microstructural level due to the local hemodynamics in the arterial lumen, as well as in evaluating the intraoperative treatment. In this work, we describe a method for assessing intracranial aneurysm through the evaluation of blood flow within the lumen and morphological structures of the arterial wall with optical coherence tomography (OCT). Sterile intravascular fiber-optic catheters can be introduced in the artery to detect blood flow. Prior to this work, limited investigations of catheter based Doppler OCT (DOCT) were reported. A novel signal processing technique was developed to further reduce the effect of Doppler noise within a catheter based DOCT system. This technique consisted of splitting the interferogram of an OCT signal prior to estimating the Doppler shift. This split spectrum DOCT (ssDOCT) method was evaluated through flow models and porcine models, as well as through the correlation between ssDOCT algorithm and computational fluid dynamic (CFD) models. It was observed that ssDOCT provided improved Doppler artefact suppression over the conventional DOCT technique. ssDOCT also provided the ability to estimate lower velocities within the DOCT image to measure the hemodynamic patterns around stent struts in both the internal carotid and patient specific flow phantoms. An OCT imaging study was also conducted consisting of surgically resected human intracranial aneurysms. Further enhancement of the detection of these key morphological structures was demonstrated by an optical-attenuation imaging variant of OCT. The presented techniques could provide further insights to the cause of intracranial aneurysm rupture and vascular healing mechanisms.