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Drug transport from blood to extravascular tissue can locally be achieved by increasing the vascular permeability through ultrasound-activated microbubbles. However, the mechanism remains unknown, including whether short and long cycles of ultrasound induce the same onset rate, spatial distribution, and amount of vascular permeability increase. Accurate models are necessary for insights into the mechanism so a microvessel-on-a-chip is developed with a membrane-free extravascular space. Using these microvessels-on-a-chip, distinct differences between 2 MHz ultrasound treatments are shown with 10 or 1000 cycles. The onset rate is slower for 10 than 1000 cycles, while both cycle lengths increase the permeability in spot-wise patterns without affecting microvessel viability. Significantly less vascular permeability increase and sonoporation are induced for 10 versus 1000 cycles at 750 kPa (i.e., the highest studied peak negative acoustic pressure (PNP)). The PNP threshold for vascular permeability increases is 750 versus 550 kPa for 10 versus 1000 cycles, while this is 750 versus 220 kPa for sonoporation. Vascular permeability increases do not correlate with α v β 3 -targeted microbubble behavior, while sonoporation correlates with α v β 3 -targeted microbubble clustering. In conclusion, the further mechanistic unraveling of vascular permeability increase by ultrasound-activated microbubbles in a developed microvessel-on-a-chip model aids the safe and efficient development of microbubble-mediated drug transport., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Photothermal optical coherence microscopy (PT-OCM) combines the high-resolution, label-free morphological imaging of OCM with the ability to discriminate tissue composition through phase-sensitive photothermal imaging. In this study, we perform 2D imaging of human carotid endarterectomies to spectrally determine lipid distribution, with verification via histologically stained samples. The structural information from OCM is combined with the spectral information gained from measuring the resulting sample surface displacement from thermoelastic expansion, following light irradiation. PT-OCM is thus demonstrated as a potential tool in the investigation of atherosclerotic plaque lipids, contributing towards the understanding of plaque instability., Competing Interests: Gijs van Soest is a cofounder of, and has equity in, Kaminari Medical BV, who were not involved in the submitted work. In the past three years, he was the PI on research projects, administered by Erasmus MC, that received research support from FUJIFILM VisualSonics, Shenzhen Vivolight, Boston Scientific, Waters and Mindray (outside the submitted work). Ton van der Steen is a cofounder of, and has equity in, Kaminari Medical BV. The other authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Multimodal intravascular ultrasound and photoacoustic (IVUS/PA) imaging is a promising diagnostic tool for cardiovascular diseases like atherosclerosis. IVUS/PA catheters typically require two independent transducers due to different frequency requirements, potentially increasing the catheter size. To facilitate multimodal imaging within conventional catheter dimensions, we designed, fabricated, and characterized a dual-transducer acoustic stack where a low-frequency (LF) PA receiver sits as a matching layer for the high-frequency (HF) US transducer. While the HF transducer operates around 50 MHz, the LF receiver targets frequencies below 15 MHz to capture most of the PA energy from atherosclerotic plaque lipids. Simulation results reveal that this configuration could increase the sensitivity of the HF transducer by 3.54 dB while maintaining bandwidth. Phantom experiments with fabricated stacks showed improved performance for the US transducer, validating the enhanced sensitivity and bandwidth. Following improvements in stack fabrication, the proposed acoustic stack is a viable design that can significantly enhance diagnostic accuracy for atherosclerosis, providing high-resolution, multifrequency imaging within a compact catheter form factor.

Intravascular ultrasound and optical coherence tomography are used with increasing frequency for the care of coronary patients and in research studies. These imaging tools can identify culprit lesions in acute coronary syndromes, assess coronary stenosis severity, guide percutaneous coronary intervention (PCI), and detect vulnerable plaques and patients. However, they have significant limitations that have stimulated the development of multimodality intracoronary imaging catheters, which provide improvements in assessing vessel wall pathology and guiding PCI. Prototypes combining 2 or even 3 imaging probes with complementary attributes have been developed, and several multimodality systems have already been used in patients, with near-infrared spectroscopy intravascular ultrasound-based studies showing promising results for the identification of high-risk plaques. Moreover, postmortem histology studies have documented that hybrid imaging catheters can enable more accurate characterization of plaque morphology than standalone imaging. This review describes the evolution in the field of hybrid intracoronary imaging; presents the available multimodality catheters; and discusses their potential role in PCI guidance, vulnerable plaque detection, and the assessment of endovascular devices and emerging pharmacotherapies targeting atherosclerosis., Competing Interests: Funding Support and Author Disclosures Prof Jaffer has received research grants from Canon, Siemens, Shockwave, Teleflex, Mercator, Boston Scientific, HeartFlow, and Neovasc; has received consultant/speaker fees from Boston Scientific, Siemens, Magenta Medical, Philips, Biotronik, Mercator, and Abiomed; has equity interest in Intravascular Imaging Inc and DurVena. Massachusetts General Hospital has licensing arrangements with Terumo, Canon, and SpectraWAVE; Dr Jaffer has the right to receive royalties. Prof Serruys has served as a consultant for Merillife, Novartis, Xeltis, SMT, and Philips. Prof Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; has served as a consultant for Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWAVE, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Prof Stone’s employer, Mount Sinai Hospital, receives research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Prof Muller is a cofounder of, has equity interest in, has served as a consultant for, and is not an employee of SpectraWAVE; and is a cofounder with no financial interest in Infraredx, Inc. Prof Van Soest is a cofounder of, consultant for, and has financial interest in Kaminari Medical BV, which develops IVPA/IVUS technology; and has received research grants from Boston Scientific. Dr Courtney is an employee of; has shareholder/equity interest in Conavi Medical Inc; and has received stock options, royalties, and research funding from Conavi Medical Inc. Prof Tearney has financial/fiduciary interest in SpectraWave, a company developing an OCT NIRS intracoronary imaging system and catheter. His financial/fiduciary interest was reviewed and is managed by Massachusetts General Brigham in accordance with their conflict of interest policies. Prof Tearney has received materials from Terumo Corporation; and has received sponsored research funding from Canon Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Spectral photoacoustic imaging in combination with unmixing techniques may be applied to retrieve information about high-risk features present in atherosclerotic plaques, possibly providing prognostic insights into future stroke events. We present the photoacoustic spectral contrast found in 12 systematically scanned advanced atherosclerotic plaques in the near-infrared wavelength range (850-1250 nm). The main absorbers are lipid, water, and hemoglobin, with the highest photoacoustic intensities at the lipid's second overtone at 1190 and 1210 nm. Linear unmixing resulted in visualizing regions with high lipid and hemoglobin absorption, corresponding to the histological presence of lipid and intraplaque hemorrhage. A non-negative matrix factorization approach reveals differences in lipid spectral contrast, providing potential insights into the vulnerability of atherosclerotic plaque. These results provide a reference for future, more complex, in vivo photoacoustic imaging of carotid artery atherosclerosis, potentially contributing to assessing the risk of future events and treatment decision., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gijs van Soest is a cofounder of, and has equity in, Kaminari Medical BV, who were not involved in the submitted work. In the past three years, he was the PI on research projects, administered by Erasmus MC, that received research support from FUJIFILM VisualSonics, Shenzhen Vivolight, Boston Scientific (outside the submitted work), Waters and Mindray (related to the submitted work). Ton van der Steen is a strategic advisor of, and has a financial interest in, Kaminari Medical BV. The other authors have no conflicts of interest to declare., (© 2024 The Authors.)

Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n = 17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n = 6), mild (n = 6), and advanced disease (n = 5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gijs van Soest is an advisor to, and has a financial interest in, Kaminari Medical BV. The other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)