SCPAT-GAN: Structural Constrained and Pathology Aware Convolutional Transformer-GAN for Virtual Histology Staining of Human Coronary OCT images

There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease. However, existing methods either require a large pixel-wisely paired training dataset or have limited capability to map pathological regions. To address these issues, we proposed a structural constrained, pathology aware, transformer generative adversarial network, namely SCPAT-GAN, to generate virtual stained H&E histology from OCT images. The proposed SCPAT-GAN advances existing methods via a novel design to impose pathological guidance on structural layers using transformer-based network.Comment: 9 pages, 4 figure

Oral antiplatelet therapy in diabetes mellitus and the role of prasugrel: an overview

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR

<p>Abstract</p> <p>Background</p> <p>Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent.</p> <p>Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model. Myocardial infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second myocardial infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of infarcts.</p> <p>Results</p> <p>Gd(ABE-DTTA) or Gd(DTPA) highlighted the acute infarct, whereas the four-week old infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean ± SD signal intensity enhancement (SIE) was 366 ± 166% and 24 ± 59% in the acute infarct and the four-week old infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 ± 124%) and four-week old infarcts (400 ± 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute infarct. The existence and localization of both infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old infarct, while the late subacute infarct showed granulation tissue and early collagen deposition.</p> <p>Conclusions</p> <p>Late enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute infarct in a reperfused, double infarct, canine model.</p

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value

MRI evaluation of a stented abdominal aorta of a rabbit

BACKGROUND MRI is an attractive non-invasive angiographic modality not requiring nephrotoxic contrast agents and damaging exposure to radiation such as traditional angiography and multislice CT. It has previously been shown to provide consistently accurate non-invasive information from the stented regions of peripheral vessels even under stenotic conditions [1-3]. The aim of this study is to show that phase contrast magnetic resonance (PC-MR) can be used to provide accurate quantitative information of blood flow in smaller stented vessels such as the coronaries, using an in-vitro model and a rabbit aorta model. The ultimate goal of the project is to evaluate in-stent restenosis in stented coronary vessels, ultimately describing the degree of stenosis based on blood velocity indices such as translesional pressure gradient and peak systolic velocity ratio (PSVR). 2. MATERIALS AND METHODS A vascular phantom was used to evaluate the signal intensity in 3.5 mm generic 54/46 NiTi stents (Boston Scientific, Natick, MA) implanted in a polyvinyl chloride tube. The phantoms were placed in the isocenter of the 3 T Philips Intera (Philips Medical Systems, Bothell, WA) for image acquisition. They were perfused with steady flow 130-160 ml/min using a flow loop with a Little giant pump (Oklahoma, OK,). The MR settings were optimized and were: slice thickness= 5 mm, pixel size= 0.39 mm, V enc= 200 cm/s, TE= 7 msec, TR= 19 msec, and flip angle= 10°. The clinical experiment consisted of 3.5 mm stents deployed in the descending aorta of New Zealand white adult rabbits. IACUC approval was received for the study. The rabbits were anesthetized, transported to the MR facility placed in the isocenter of the 3 T Philips Intera. The MR settings for the rabbit experiment were: slice thickness = 2 mm, TE= 4 msec, TR= 6 msec, pixel size= 0.29, V enc= 150 cm/s and flip angle = 10°. Flow velocities were calculated using the raw PC-MR images and the equation: V = V enc × φ v/180° (1) Where φ v is the phase shift, (180° to -180°), V enc is the encoding velocity and V is the velocity of blood flow calculated by PC-MR. 3. RESULTS The phantom studies provided excellent visibility in the stented region as shown by the modulus (a) and phase contrast (b) images in Fig. 1. Fig. 2 shows the velocity profile in the lumen voxel by voxel from the PC-MR images calculated using equation 1. There were 29 voxels inside the stented region that provided useful signal. The presence of the stent does not impair the signal from voxels in the center of the lumen, but impairs the ability to receive a signal from voxels close to the vessel wall and stent. The comparison indicates good agreement with the theoretical Hagen Poiseuille profile. The average velocity of 35 cm/s is in good agreement with the actual flow (160 ml/min). Similar results were observed in the clinical studies. Fig. 3 shows the modulus images and Fig. 4 the PC-MR images inside and outside the stented region in the rabbit abdominal aorta. The out of stent plane was taken just upstream of the stented area. Excellent lumen visibility is observed in the stented area. Table 1 shows the comparison from 3 experiments when the Region of interest (ROI) is increased from a few voxels at the centerline of the lumen, to the whole useful signal area in the whole lumen. Fig. 5 shows the time velocity history of blood flow throughout the cardiac cycle. This calculation considers all voxels within the lumen and as a result the blood flow in the stented region is underestimated in comparison to the unstented area in the vessel since little signal is received from voxels near the wall. 4. CONCLUSIONS Lumen visibility and measurement of blood flow velocity in stented coronary arteries may be possible by PC-MR. Velocity calculation is more accurate at the center of the vessel since there is signal loss from voxels near the stented wall. This shows promise that MR magnitude images and PC-MR can be used in the non-invasive assessment of stented lumen patency and in-stent restenosis

Comparative computational fluid dynamics and experimental phase-contrast MRI: evaluations of in-stent restenosis

While angiography and other translesional catheter-based assessments of stented peripheral vasculature are currently used in clinical applications, a quantitative non-invasive imaging modality would improve the treatment of intermediate levels of in-stent restenosis (ISR). The use of magnetic resonance imaging (MRI), in metal stents has been limited due to magnetic susceptibility artifacts and radiofrequency shielding effects. However, MRI compatible materials such as nickel-titanium alloys used in stents have shown superior lumen visibility. In this study, we used phase contrast MRI in a flow phantom of three different geometries of stenosis: a) 90% axisymmetric, b) 75% axisymmetric and c) 50% asymmetric. The velocity distribution was obtained at 3 different locations inside the stent. This was compared with an equivalent computational fluid dynamics (CFD) model of the same stenotic geometries

Severe, diffuse coronary artery spasm after drug-eluting stent placement

OBJECTIVES: Three cases of severe, diffuse coronary artery spasm after drug-eluting stent placement at our institution prompted this review. BACKGROUND: Drug-eluting stents have gained widespread use due to extraordinarily low rates of restenosis. Despite these generally superior clinical outcomes, the specter of rare idiosyncratic reactions remains a concern. METHODS: We performed searches of Medline and the U.S. FDA Manufacturer And User facility Device Experience database (MAUDE) to identify and describe spasm after coronary stent placement. Searches included drug-eluting and bare-metal stents. Institutional cases are reviewed. Location, time course and outcome of cases are described. RESULTS: Thirteen cases of spasm were identified after stent placement. Seven cases occurred after Cypher™ drug-eluting stent placement, 2 after Taxus® drug-eluting stent placement, 1 after BiodivYsio™ and 3 after bare-metal stents. Five patients experienced diffuse, multivessel spasm, 2 after Cypher, 2 after Taxus, and 1 after a Velocity™ stent. Of these 5 patients, 2 died. An additional 2 required intra-aortic balloon pump placement for cardiogenic shock. Another had persistent symptomatic, diffuse coronary spasm documented by angiography at 1 year. CONCLUSIONS: We describe coronary spasm after stent placement, particularly after drug-eluting stents. Outcomes associated with diffuse severe spasm after stenting are poor, and the pathophysiology remains poorly understood