Detection of Individual Microbubbles of Ultrasound Contrast Agents

Klibanov, Alexander L.; Rasche, Peter T; Hughes, Michael S.; Wojdyla, Jolette K.; Galen, Karen P.; Wible, James H.; Brandenburger, Gary H.

doi:10.1097/01.rli.0000115926.96796.75

Cited by 187 publications

(126 citation statements)

References 21 publications

(22 reference statements)

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“…The maximum response (e f % 35%, e 2f % 11%) can be found for microbubbles with a radius of $3.4 lm, which is a typical resonant size for a driving frequency of 1 MHz, as reported previously. 23,27 The experimental data showed good agreement with the simulation results. Figures 3(c) and 3(d) illustrates the asymmetric vibrational response, indicated by the difference between the relative amplitude of the expansion and the compression phase (A exp À A com ), versus bubble size R meas .…”

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confidence: 68%

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Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Luan

Renaud

Raymond

et al. 2016

Applied Physics Letters

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In this study we present a combined optical sizing and acoustical characterization technique for the study of the dynamics of single freely-floating ultrasound contrast agent microbubbles exposed to long burst ultrasound excitations up to the milliseconds range. A co-axial flow device was used to position individual microbubbles on a streamline within the confocal region of three ultrasound transducers and a high-resolution microscope objective. Bright-field images of microbubbles passing through the confocal region were captured using a high-speed camera synchronized to the acoustical data acquisition to assess the microbubble response to a 1-MHz ultrasound burst. Nonlinear bubble vibrations were identified at a driving pressure as low as 50 kPa. The results demonstrate good agreement with numerical simulations based on the shell-buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499–3505 (2005)]. The system demonstrates the potential for a high-throughput in vitro characterization of individual microbubbles.

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confidence: 68%

“…23 The vibrational response (radius-time curve) of a total of 72 single microbubbles to a 1 MHz ultrasound burst with a peak negative pressure of 50 kPa was measured and analyzed. The measured resting radius (R meas ) of each microbubble was estimated from a selected in-focus image from an optical recording using an edge-tracking minimum cost algorithm.…”

mentioning

confidence: 99%

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Luan

Renaud

Raymond

et al. 2016

Applied Physics Letters

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“…"Although a single unit of contrast is on the order of 0.25 to 1 µm in diameter, the generated acoustic perturbation appears much larger" . Therefore, theoretically ultrasound-based techniques have the potential to detect a single cell loaded with a single unit of contrast Klibanov, Rasche et al 2004). However, techniques to intracellular ultrasound contrast labeling are not yet robust, and more importantly, their possible effects on cell function are not yet identified.…”

Section: Ultrasoundmentioning

confidence: 99%

Clinical Stem Cell Imaging and In vivo Tracking

Mirpour¹,

Gholamrezanezhad²

2011

Stem Cells in Clinic and Research

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“…Echocardiography therefore has the potential to detect a single cell loaded with a single unit of contrast. 17 Nevertheless, methods to accumulate contrast intracellularly are not yet robust, and effects on cell motility, etc, are not known. An additional problem is that echogenic contrast agents cast an acoustic "shadow" below the first unit of contrast detected, thus precluding accurate quantification of cell number.…”

Section: Ultrasoundmentioning

confidence: 99%

In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease

2004

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Abstract-Various stem cells hold promise for the treatment of human cardiovascular disease. Regardless of stem cell origin, future clinical trials will require that the location and number of such cells be tracked in vivo, over long periods of time. The problem of tracking small numbers of cells in the body is a difficult one, and an optimal solution does not yet exist. We review the many contrast agents and detectors that have been proposed for stem cell tracking during clinical trials, define the characteristics of an ideal imaging technology, and suggest future directions for research. For example, stem cell therapy for heart failure addresses an important problem in clinical medicine. Heart failure is a major cause of morbidity and mortality in the United States. The rates of new and recurrent heart failure events increase substantially with age. In patients aged 65 and older, congestive heart failure is the single most frequent cause of hospitalization in the United States. Despite substantial advances in the clinical management of heart failure, the diagnosis continues to carry a grave prognosis with an overall 5-year mortality rate of Ϸ50%. This rate is substantially worse in more severely affected patient subsets. An understanding of the role of stem cells in repopulating damaged areas in the heart would help target these diseased areas. 1 The problem of imaging small numbers of cells in the living subject is not limited to stem cell-based treatments in cardiology but has broad applicability in oncology, immunology, and transplantation. Ideal Imaging Technology for Stem Cell TrackingSuccessful in vivo imaging requires that a contrast agent associated with a stem cell exert an "effect size" sufficient for detection by imaging hardware. Although the most attractive contrast agents for tracking are endogenous ones (ie, normal components of the stem cell), their effect size is extremely small. This review will focus on exogenous contrast agents, which have a large and controllable effect size. It also will focus on imaging technology that has clinical relevance because many preclinical small animal studies in the field of stem cell tracking are not translatable to clinical practice. The 8 characteristics of an ideal imaging technology for stem cell tracking are presented in Table 1. First, and foremost, the exogenous contrast agent must be biocompatible, safe, and nontoxic. This is especially important when nanotechnology solutions to the tracking problem (mentioned below) are considered, because most solid-state devices will be composed of materials that do not have proven long-term safety in vivo.Another consideration is the need for genetic modification of the stem cell or perturbation of its genetic program by the contrast agent itself. Several imaging techniques, such as enzymatic conversion of an injected substrate and receptorbased binding, require stable integration of transgenes. This strategy may be combined with genetic manipulation of stem cell populations to enhance the viability, differentiatio...

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Detection of Individual Microbubbles of Ultrasound Contrast Agents

Abstract: Ultrasound medical systems can resolve backscatter signals from individual microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.

Cited by 187 publications

References 21 publications

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Clinical Stem Cell Imaging and In vivo Tracking

In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease

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