http://academic.oup.com/auk/article-pdf/102/3/661/30080634/auk0661.pdf

Scaling: why is animal size so important?

Molecular ultrasound imaging: current status and future directions

The contrast agent Definity™ has recently been shown to have substantial nonlinear activity at high ultrasound frequencies (>10 MHz). In this study, measurements were performed to characterize the frequency dependant attenuation properties of Definity™ and populations of Definity™ that had been modified to preferentially isolate smaller bubbles through decantation or mechanical filtration. A narrowband pulse-echo substitution method was employed with a series of four transducers covering the frequency range from 2 to 50 MHz. “Native” Definity™ has peak in attenuation in the vicinity of 10 MHz and remains high until 50 MHz. This pattern is significantly different from other clinically approved agents and is consistent with recent reports of nonlinear activity at high frequencies. With increasing decantation times, the attenuation peak becomes more diffuse and occurs at progressively higher frequencies. By 3 h for example, attenuation continues to rise until 30 MHz. The bubble size distribution undergoes preferential skewing toward smaller bubbles with increasing decantation time. Between 30 s and 3 h, the mean bubble diameter goes from 3.99 to 0.98 micrometers. Mechanical filtration with 2 and 1 μm pores causes attenuation to rise until 15 and 40 MHz, respectively. Definity™ can therefore be manipulated to improve its relative activity at higher frequencies (>10 MHz), which has implications for ultrasound biomicroscopy and intravascular ultrasound applications. Further, these results suggest that agent handling can have a substantial impact on size distributions affecting lower frequency applications. Shell friction estimates derived from these data are lower than those reported for larger bubbles at lower frequencies.

Attenuation and Size Distribution Measurements of Definity™ and Manipulated Definity™ Populations

Response of contrast agents to ultrasound

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.

https://www.pnas.org/content/pnas/109/30/E2033.full.pdf

Tumor radiation response enhancement by acoustical stimulation of the vasculature

It was previously shown that it is possible to produce nonlinear scattering from microbubble contrast agents using transmit frequencies in the 14-32 MHz range, suggesting the possibility of performing high-frequency, nonlinear microbubble imaging. In this study, we describe the development of nonlinear microbubble B-scan imaging instrumentation capable of operating at transmit center frequencies between 10 and 50 MHz. The system underwent validation experiments using transmit frequencies of 20 and 30 MHz. Agent characterization experiments demonstrate the presence of nonlinear scattering for the conditions used in this study. Using wall-less vessel phantoms, nonlinear B-scan imaging is performed using energy in one of the subharmonic, ultraharmonic, and second harmonic frequency regions for transmit frequencies of 20 and 30 MHz. Both subharmonic and ultraharmonic imaging modes achieved suppression of tissue signals to below the noise floor while achieving contrast to noise ratios of up to 26 and 17 dB, respectively. The performance of second harmonic imaging was compromised by nonlinear propagation and offered no significant contrast improvement over fundamental mode imaging. In vivo experiments using the subharmonic of a 20 MHz transmit pulse show the successful detection of microvessels in the rabbit ear and in the mouse heart. The results of this study demonstrate the feasibility of nonlinear microbubble imaging at high frequencies

High frequency nonlinear B-scan imaging of microbubble contrast agents

Limited access to comprehensive assessment of physiological disorders of the upper aerodigestive tract by different specialties represents a barrier to care in rural healthcare settings, which may lead to misdiagnosis, underdiagnosis, and increased associated mortality. No single differential diagnostic exam for the comprehensive assessment of all functions of the upper aerodigestive tract is available to bridge this gap. We present a single procedure for assessment of physiological functions of the upper aerodigestive tract including swallow, voice, respiration, and cough while also screening for gastric retention and obstructive sleep apnea which might contribute to these disorders. Our procedure, called Aerodigestoscopy (ADS), represents a procedure incorporating other established exams as integral components to evaluate patients with aerodigestive disorders. Patients who might particularly benefit from our ADS diagnostic algorithm are those in a rural community referred by other health professionals due to complaints of aerodigestive symptoms and signs. We present a brief overview of how the procedure was developed, what it includes, and retrospective safety data from over 18,000 ADS procedures performed over the last 10 years, demonstrating safety and feasibility of this procedure.

Aerodigestoscopy (ADS): A retrospective examination of the feasibility, safety, and comfort of a new procedure for the evaluation of physiological disorders of the aerodigestive tract

A.S. Brown

Papers

High frequency nonlinear B-scan imaging of microbubble contrast agents

Aerodigestoscopy (ADS): A retrospective examination of the feasibility, safety, and comfort of a new procedure for the evaluation of physiological disorders of the aerodigestive tract