Intravascular ultrasound molecular imaging of atheroma components in vivo

Hamilton, Andrew J.; Huang, Shaoling; Warnick, Drew; Rabbat, Mark; Kane, Bonnie J.; Nagaraj, Ashwin; Klegerman, Melvin E.; McPherson, David D.

doi:10.1016/j.jacc.2003.07.048

Cited by 200 publications

(184 citation statements)

References 27 publications

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“…They can be conjugated with antibodies for targeted delivery. 22,34 Other investigators have employed similar strategies using immunoliposomes targeted to inflammation in myocardial infarction. Third, ELIP can have both hydrophobic and hydrophilic cores due to its …”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Kim¹,

Britton²,

Peng³

et al. 2013

IJN

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Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment.

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Section: Discussionmentioning

confidence: 99%

“…20 We have recently developed a novel methodology to encapsulate bioactive gases replacing air into our liposomal nanovehicles. [21][22][23][24][25] Coencapsulation of NO with argon enabled us to adjust the amount of encapsulated NO. A total of 10 µL of gas was encapsulated into 1 mg of liposomes.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Kim¹,

Britton²,

Peng³

et al. 2013

IJN

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“…75 Subsequently, these phagocytosed microbubbles generate characteristic echogenic features that can be used to identify their distribution within the plaque with realtime intravascular ultrasonography. [76][77][78] Vavuranakis et al 76 used contrast enhancement with microbubbles in both animal and human models to detect blood flow into the coronary lumen and perivascular flow, as part of contrast-enhanced sonographic images. 79 In a porcine model, 11 regions of interest within the left anterior descending coronary arteries and left circumflex arteries, including perivascular structures, were compared with corresponding gray-scale intravascular sonography levels before and after the injection of SonoVue contrast (0.06 mL/kg; Bracco Diagnostics, Princeton, New Jersey).…”

Section: Microbubblesmentioning

confidence: 99%

Intravascular Ultrasound: Principles and Cerebrovascular Applications

Zacharatos¹,

Hassan²,

Qureshi³

2010

AJNR Am J Neuroradiol

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SUMMARY: Intravascular sonography is a valuable tool for the morphologic assessment of coronary atherosclerosis and the effect of pharmacologic and nonpharmacologic interventions on the progression or stabilization of atherosclerosis. An analysis of the different modes, applications, and limitations is provided on the basis of review of existing data from multiple clinical case studies, trials, and mechanistic studies. Intravascular sonography has been used to assess the outcomes of different percutaneous interventions, including angioplasty and stent implantation, and to provide detailed characterization of atherosclerotic lesions, aneurysms, and dissections within the cerebrovascular circulation. Evolution of intravascular sonographic technology has led to the development of more sophisticated diagnostic tools such as color-flow, virtual histology, and integrated backscatter intravascular sonography. The technologic advancement in intravascular sonography has the potential of providing more accurate information prior, during, and after a medical or endovascular intervention. Continued assessment of this diagnostic technique in both the intracranial and extracranial circulation will lead to increased use in clinical practice with the intent to improve outcomes.ABBREVIATIONS: CI ϭ confidence interval; EEL ϭ external elastic lamina; O.D. ϭ outer diameter C urrently there are 3 types of sonography used to assess the extracranial and the intracranial circulation: 1) transcranial Doppler, 2) B-mode sonography, and 3) intravascular sonography (Table). The morphologic appearance of the intra-arterial and intravenous circulation can now be visualized by using intravascular sonography, which has become a commonly used diagnostic technique for randomized clinical trials assessing coronary plaque progression and regression. With excellent resolution, intravascular sonography provides cross-sectional images of both the arterial wall and lumen and identifies intimal flaps and irregularities, and the composition and extent of the atherosclerotic plaque.2-6 Evolution of the intravascular sonography technology has led to the development of more sophisticated diagnostic tools such as colorflow, virtual histology, and integrated backscatter intravascular sonography. 7 The successful application of conventional (gray-scale) intravascular sonography in the coronary arteries has led to its application within the extracranial and intracranial arteries. Recently, intravascular sonography has also been used to identify and characterize carotid artery aneurysm, dissection, and thrombus. 8 Intravascular sonography has been used successfully to assist in making measurements before and after percutaneous transluminal balloon angioplasty and stent placement, with emphasis on the identification of stent underexpansion, poor apposition, subacute stent thrombosis, and plaque protrusion.9,10 Real-time dynamic intravascular sonography of the cervical common carotid artery and internal carotid artery can detect defects that are not readily appar...

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“…The inflammation response to atherosclerosis was detected using VCAM-1, ICAM-1, and P-selectin targeted microbubbles in a murine model [39], [40], [86], a swine model [87] and a primate model [88]. Myocardial ischemia was detected using P-selectin and/or E-selectin targeted microbubbles in a murine model [37], [38], [89], a rat model [90], [91], and a primate model [92].…”

Section: Molecular Imaging Of Inflammationmentioning

confidence: 99%

“…Additionally, inflammatory bowel disease was imaged using Pselectin and E-selectin targeted microbubbles in a murine model [93], [94] and a swine model [95]. Dual-targeted microbubbles were utilized to further enhance targeting [40], [87]- [89], [91], [92], [94].…”

Section: Molecular Imaging Of Inflammationmentioning

confidence: 99%

Quantitative Ultrasound Molecular Imaging in Large Blood Vessel Environments

Wang

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Stroke is the fourth leading cause of death in the United States. The current standard of care for carotid atherosclerosis addresses the disease after the plaque has developed to the point at which it is detectable using anatomical-based imaging to measure luminal stenosis. Ultrasound molecular imaging, possessing the ability to image the molecular signature of early vascular inflammation, potentially decades prior to the formation of plaque, may enable more timely diagnosis and treatment of atherosclerosis and atherosclerotic risk. Additionally, it simultaneously meets the needs for rapid, lowcost, and radiation-free molecular marker detection that may facilitate clinical adoption. Unfortunately, existing ultrasound-based molecular imaging is limited to small blood vessel environments, and unable to measure molecular marker concentration in large blood vessels.In the first part of the dissertation, the design, implementation, and validation of a In the second part of the dissertation, the characterization of an expanding-nozzle flow-focusing microfluidic device for the generation of monodisperse microbubbles is ii presented. Significantly, the characterization could facilitate real-time adjustment of microbubble diameter and production rate using microfluidic devices.iii

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Intravascular ultrasound molecular imaging of atheroma components in vivo

Abstract: It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.

Cited by 200 publications

References 27 publications

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Intravascular Ultrasound: Principles and Cerebrovascular Applications

Quantitative Ultrasound Molecular Imaging in Large Blood Vessel Environments

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