Super-resolution ultrasound microvessel imaging with contrast microbubbles has recently been proposed by multiple studies, demonstrating outstanding resolution with high potential for clinical applications. This study aims at addressing the potential noise issue in in vivo human super-resolution imaging with ultrafast plane wave imaging. The rich spatiotemporal information provided by ultrafast imaging presents features that allow microbubble signals to be separated from background noise. In addition, the high frame rate recording of microbubble data enables the implementation of robust tracking algorithms commonly used in particle tracking velocimetry. In this study, we applied the nonlocal means (NLM) denoising filter on the spatiotemporal domain of the microbubble data to preserve the microbubble tracks caused by microbubble movement and suppress random background noise. We then implemented a bipartite graph-based pairing method with the use of persistence control to further improve the microbubble signal quality and microbubble tracking fidelity. In an in vivo rabbit kidney perfusion study, the NLM filter showed effective noise rejection and substantially improved microbubble localization. The bipartite graph pairing and persistence control demonstrated further noise reduction, improved microvessel delineation and a more consistent microvessel blood flow speed measurement. With the proposed methods and freehand scanning on a free-breathing rabbit, a single microvessel cross-section profile with full width at half maximum of 57 μm could be imaged at approximately 2 cm depth (ultrasound transmit center frequency = 8 MHz, theoretical spatial resolution ~200 μm). Cortical microvessels that are 76 μm apart can also be clearly separated. These results suggest that the proposed methods have good potential in facilitating robust in vivo clinical super-resolution microvessel imaging.

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Fatal cerebrovascular events are often caused by rupture of atherosclerotic plaques. However, ruptureprone plaques are often distinguished by their internal composition rather than degree of luminal narrowing, and conventional imaging techniques might thus fail to detect such culprit lesions. In this feasibility study, we investigate the potential of ultrasound shear wave elastography (SWE) to detect vulnerable carotid plaques, evaluating group velocity and frequency-dependent phase velocities as novel biomarkers for plaque vulnerability. In total, 27 carotid plaques from 20 patients were scanned by ultrasound SWE and magnetic resonance imaging (MRI). SWE output was quantified as group velocity and frequency-dependent phase velocities, respectively, with results correlated to intraplaque constituents identified by MRI. Overall, vulnerable lesions graded as American Heart Association (AHA) type VI showed significantly higher group and phase velocity compared to any other AHA type. A selection of correlations with intraplaque components could also be identified with group and phase velocity (lipid-rich necrotic core content, fibrous cap structure, intraplaque hemorrhage), complementing the clinical lesion classification. In conclusion, we demonstrate the ability to detect vulnerable carotid plaques using combined SWE, with group velocity and frequency-dependent phase velocity providing potentially complementary information on plaque characteristics. With such, the method represents a promising non-invasive approach for refined atherosclerotic risk prediction. Atherosclerotic disease is recognized as a diffuse systemic vascular process, and rupture and erosion of carotid atherosclerotic plaques is the number one cause of cerebrovascular mortality in the world 1. Fatal plaque-related events however often arise without prior symptoms 2 , and the task of plaque risk stratification-identifying rupture-prone vulnerable plaques from stable rupture-resistant phenotypes-is of pivotal clinical importance. Surgical endarterectomy is recommended on the basis of carotid stenosis 3 , however it has been extensively shown that vulnerable plaques are rather identified by their composition than on their extent of luminal obstruction 4,5. Several studies have shown that in the majority of patients with acute ischemic syndromes culprit coronary sites had less than 50-70% diameter narrowing, and plaques producing non-flow-limiting stenosis accounted for more

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Type 2 diabetes mellitus patients are at increased risk for macrovascular and microvascular complications. Both in vivo and in vitro studies of small arteries and arterioles of diabetic subjects demonstrate impaired endothelial function without anatomic lesions. Coronary flow reserve (CFR) is a surrogate marker of coronary microcirculatory endothelial function in diabetic patients without significant stenosis of the associated epicardial coronary artery. Glycosylated hemoglobin A1c is related to likelihood of occurrence of microvascular events. The objective of this article is to report on recent developments in multiple noninvasive techniques to assess CFR and their use in aiding the understanding of the relationship of CFR, glycemic control and cardiovascular outcomes.

Purpose: Infarct mass as assessed by myocardial-delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT-MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT-MPE with CMR for prediction of cardiac events in reperfused STEMI patients. Materials and Methods:Consecutive STEMI patients with early reperfusion were studied. RT-MPE and CMR were performed. Perfusion score indices (PSI RT-MPE and PSI CMR ) were calculated [sum of segmental perfusion scores/number of segments].CMR infarct mass (g) and RT-MPE myocardial blood flow (MBF dB/s) were quantified.Patients were followed for cardiac events (death, nonfatal MI, revascularization, angina, and heart failure).Results: All 27 patients (age 62±14; follow-up 3.5±2.6 years) had thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct vessel. Cardiac events occurred in 17 (63%). Cardiac event patients had higher PSI RT-MPE , PSI CMR , infarct mass, and lower MBF. PSI RT-MPE cutoff of 0.3 had an AUC of 0.856 (82% sensitivity, 70% specificity), while a PSI CMR cutoff of 0.2 had an AUC of 0.765 (76% sensitivity, 60% specificity).Infarct mass and MBF were independent predictors of cardiac events after adjusting for risk factors (hazard ratios: 20.9 [95% CI 1.8-256] P=. P=.01, respectively). Conclusions:Quantitative RT-MPE performed comparably to CMR for prediction of MACE in STEMI patients supporting a prognostic role for this noninvasive, bedside imaging method. K E Y W O R D Smajor adverse cardiac events, microvascular obstruction, outcomes research, perfusion imaging, prognosis, ST elevation myocardial infarction