A nanoscale Ti∕GaAs metal-semiconductor hybrid sensor for room temperature light detection.

We report an individually addressable Ti∕GaAs metal-semiconductor hybrid optical nanosensor with positive photoresistance and a sensitivity that increases as the device dimensions shrink. The underlying physics relates to the crossover from ballistic to diffusive transport of the photoinduced carriers and the geometric enhancement of the effect associated with a Schottky-barrier-coupled parallel metal shunt layer. For a 250 nm device under 633 nm illumination we observe a specific detectivity of D(*)=5.06×10(11) cm √Hz∕W with a dynamic response of 40 dB.

Real-time calculation of a limiting form of the Renyi entropy applied to detection of subtle changes in scattering architecture.

Previously a new method for ultrasound signal characterization using entropy H(f) was reported, and it was demonstrated that in certain settings, further improvements in signal characterization could be obtained by generalizing to Renyi entropy-based signal characterization I(f)(r) with values of r near 2 (specifically r=1.99) [M. S. Hughes et al., J. Acoust. Soc. Am. 125, 3141-3145 (2009)]. It was speculated that further improvements in sensitivity might be realized at the limit r-->2. At that time, such investigation was not feasible due to excessive computational time required to calculate I(f)(r) near this limit. In this paper, an asymptotic expression for the limiting behavior of I(f)(r) as r-->2 is derived and used to present results analogous to those obtained with I(f)(1.99). Moreover, the limiting form I(f,infinity) is computable directly from the experimentally measured waveform f(t) by an algorithm that is suitable for real-time calculation and implementation.

Application of Renyi entropy for ultrasonic molecular imaging.

Previous work has demonstrated that a signal receiver based on a limiting form of the Shannon entropy is, in certain settings, more sensitive to subtle changes in scattering architecture than conventional energy-based signal receivers [M. S. Hughes et al., J. Acoust. Soc. Am. 121, 3542-3557 (2007)]. In this paper new results are presented demonstrating further improvements in sensitivity using a signal receiver based on the Renyi entropy.

Properties of an entropy-based signal receiver with an application to ultrasonic molecular imaging.

Qualitative and quantitative properties of the finite part, H(f), of the Shannon entropy of a continuous waveform f(t) in the continuum limit are derived in order to illuminate its use for waveform characterization. Simple upper and lower bounds on H(f), based on features of f(t), are defined. Quantitative criteria for a priori estimation of the average-case variation of H(f) and log E(f), where E(f) is the signal energy of f(t) are also derived. These provide relative sensitivity estimates that could be used to prospectively choose optimal imaging strategies in real-time ultrasonic imaging machines, where system bandwidth is often pushed to its limits. To demonstrate the utility of these sensitivity relations for this application, a study designed to assess the feasibility of identification of angiogenic neovasculature targeted with perfluorocarbon nanoparticles that specifically bind to alpha(v)beta3-integrin expression in tumors was performed. The outcome of this study agrees with the prospective sensitivity estimates that were used for the two receivers. Moreover, these data demonstrate the ability of entropy-based signal receivers when used in conjunction with targeted nanoparticles to elucidate the presence of alpha(v)beta3 integrins in primordial neovasculature, particularly in acoustically unfavorable environments.

Effects of tissue anisotropy and contrast acoustic properties on myocardial scattering in contrast echocardiography.

In this study we explored the potential effects that tissue anisotropy, in conjunction with the acoustic properties of contrast, may have on quantitative measurements of myocardial perfusion with the use of ultrasonic contrast agents. We used a computer simulation of the parasternal short-axis view, based on previously measured values for the anisotropy of backscatter and attenuation of myocardium, to predict the backscattered energy from 18 specific regions within the heart before and after myocardial contrast perfusion. Results demonstrated a regional variation of contrast enhancement in the short-axis view and variations caused by incremental increases in contrast level for specific myocardial regions. Thus quantitative assessment of myocardial perfusion with contrast echocardiography is influenced by the anisotropic properties of the myocardium, and the resulting postcontrast image will depend on the interaction between tissue properties and contrast acoustic properties. The degree of myocardial enhancement caused by the presence of contrast may depend on the spatial position of the specific region investigated with respect to the transducer and the amount of contrast in the myocardium.

In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy.

Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.

Effects of tissue anisotropy on the spectral characteristics of ultrasonic backscatter measured with a clinical imaging system.

In this paper, we report the effects of inherent tissue anisotropy on the spectral properties of backscattered ultrasound when measured with a commercially-available imaging system. We insonified five specimens of bovine tendon immersed in a water tank and rotated in 10 degrees increments while being imaged with a Hewlett-Packard Sonos 1500 system. The backscattered RF signals corresponding to each angle of insonification were digitized and the spectral characteristics of the backscattered ultrasound were determined. The mean anisotropy, defined as the average difference between values at perpendicular and parallel insonification, for band-limited estimates of backscattered power, centroid frequency, upper-band to lower-band power ratio, and upper-band to total-band power ratio were found to be 24.6 +/- 1.1 dB, 142 +/- 27 kHz, 32 +/- 13%, and 22 +/- 5%, respectively (mean +/- SE). The magnitude of each of these backscatter spectral parameters was larger at perpendicular insonification compared with the corresponding values at parallel insonification, consistent with previous measurements of the inherent anisotropy of ultrasonic attenuation and backscatter in tissue.

High-frequency ultrasonic detection of thrombi with a targeted contrast system.

Site-targeted acoustic contrast agents used in conjunction with high-frequency intravascular ultrasound have the potential to localize and characterize intravascular pathology. The present study quantifies the utility of a novel, site-targeted ultrasonic contrast agent with high-frequency ultrasound (30 to 50 MHz) and demonstrates the feasibility of the new agent for augmenting detection of targeted pathology with intravascular ultrasonic catheters. High-frequency acoustic microscopy was used to image avidinconjugated nitrocellulose membranes after exposure to a control or biotinylated contrast agent. Increases (p < 0.05) in backscattered power of approximately 66 dB (4-fold) were found for the biotinylated, but not the control contrast agent. Intravascular ultrasonic images (30 MHz nominal center frequency) of plasma clots after exposure to the targeted contrast agent were brighter (p < 0.05) than in controls. These results demonstrate high-frequency acoustic enhancement with a novel targeted contrast agent and may extend the potential diagnostic spectrum of intravascular ultrasound.

A novel site-targeted ultrasonic contrast agent with broad biomedical application.

BACKGROUND: In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound to a surface or itself. METHODS AND RESULTS: In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emulsion manifested significant ultrasonic backscatter until avidin was added. Avidin-induced aggregation produced a marked enhancement in backscatter from the biotinylated but not from the control emulsion. In study 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoustic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arterial thrombi were created in dogs and then exposed to antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was administered either in situ or systemically. At baseline, all thrombi were undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control thrombi remained acoustically undetectable. CONCLUSIONS: These data provide the first in vivo demonstration of a site-specific ultrasonic contrast agent and have potential for improved sensitivity and specificity for noninvasive diagnosis of thrombi and other pathological diseases.

Frequency dependence of acoustic backscatter from 5 to 65 MHz (0.06 < ka < 4.0) of polystyrene beads in agarose.

Attenuation and compensated backscatter from suspensions of random distributions of polystyrene beads in agarose are reported across a broad, continuous range of frequencies including frequencies which are currently of interest in the emerging fields of acoustic backscatter microscopy and intravascular imaging. Data are reported over the range of ka from 0.06 to 4, where k is the magnitude of the ultrasonic wave vector and a is the radius of the beads. The attenuation coefficient exhibits a linear dependence on frequency for ka < < 1 and more complex behaviour at larger values of ka. The measured frequency dependence of the compensated backscatter was consistent with the frequency dependence of the differential backscatter cross section for a single polystyrene sphere throughout the range of ka investigated.

Technique for transrectal ultrasonography of the cranial mesenteric artery of the horse.

Transrectal ultrasonography was successfully used to image the cranial mesenteric artery and its branches in 23 adult horses. The artery could be imaged from its origin at the aorta distally to identify several bifurcations. The method for transrectal imaging of the cranial mesenteric artery and its major branches required 3 distinct transducer positions. One position was used to locate the cranial mesenteric artery by imaging the caudal portion of the aorta from the aortic bifurcation cranially to the level of the cranial mesenteric artery. The second position was used to image the origin of the cranial mesenteric artery. The third position was used to image the major branches of the cranial mesenteric artery.

Transrectal ultrasonography of the cranial mesenteric artery of the horse.

Transrectal ultrasonography was performed on the cranial mesenteric artery and its major branches in 23 conscious adult horses. Ultrasonographically, 25 arterial segments were classified as either normal or abnormal. These ultrasonographic classifications were later compared with the gross and histologic evaluations of each artery following necropsy of each horse. In this study, transrectal ultrasonography as a diagnostic test for verminous arteritis had a 90% sensitivity for detecting normal arteries and an 86% specificity for detecting abnormal arteries, suggesting that ultrasonography may be useful in the antemortem diagnosis of verminous arteritis.

In vitro ultrasonographic appearance of the normal and verminous equine aorta, cranial mesenteric artery, and its branches.

Ninety-one equine aortic and cranial mesenteric arterial segments were evaluated ultrasonographically in a water bath. On the basis of pathologic evidence of verminous arteritis, arterial segments were classified into 4 categories, and the ultrasonographic characteristics of each group were evaluated. Normal arteries (class 1) were ultrasonographically characterized by a smooth luminal surface layer and uniform wall thickness and echogenicity. Arteries with only histopathologic evidence of verminous arteritis (class 2) were ultrasonographically characterized by a smooth luminal surface layer, uniform hyperechoic luminal layer. Arteries with both gross and histopathologic evidence of verminous arteritis (class 3) were characterized ultrasonographically by an irregular luminal surface layer, varying wall thickness, varying wall echogenicity, and the presence of a hyperechoic luminal layer. The ultrasonographic characteristics of arteries with luminal thrombosis (class 4) were an irregular luminal surface, varying wall thickness, and nonuniform echogenicity.

Inhibition of hamster buccal pouch carcinogenesis by 13-cis-retinoic acid.

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the left buccal pouch was painted three times weekly with a 0.5% solution of DMBA in heavy mineral oil. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice a week by pipette. Carcinogen retinoid were administered on alternate days. Group 3 animals served as controls, receiving only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group (two males and two females) were killed at 10, 12, 14, and 16 weeks. The Group 2 animals, which received 13-cis-retinoic acid, exhibited a significant delay in DMBA carcinogenesis of buccal pouch mucosa, as studied both grossly and histologically. Both groups eventually demonstrated well-differentiated epidermoid carcinomas, but the tumors were smaller in the DMBA-retinoid animals.

Retinoid inhibition of lingual carcinogenesis.

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the right posterior lateral border of the tongue was painted three times weekly with a 0.5 percent solution of DMBA in acetone. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice weekly by pipette. Carcinogen and retinoid were administered on alternate days. Group 3 animals received only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group were killed at 12, 14, 16, and 18 weeks. The Group 2 animals, receiving 13-cis-retinoic acid, exhibited a significant delay in the development of lingual tumors, both grossly and microscopically. At 14 weeks carcinomas were found in the DMBA animals, but only dysplasia and areas of carcinoma in situ were found in the DMBA-retinoid animals. After 18 weeks the DMBA animals exhibited large lingual tumors with surfacenecrosis, while the DMBA-retinoid animals presented smaller tumors with less invasion of underlying tissue.