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Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors.

ABSTRACT: Diagnosing tumors at an early stage when they are easily curable and may not require systemic chemotherapy remains a challenge to clinicians. In order to improve early cancer detection, gas filled hollow boron-doped silica particles have been developed, which can be used for ultrasound-guided breast conservation therapy. The particles are synthesized using a polystyrene template and subsequently calcinated to create hollow, rigid nanoporous microspheres. The microshells are filled with perfluoropentane vapor. Studies were performed in phantoms to optimize particle concentration, injection dose, and the ultrasound settings such as pulse frequency and mechanical index. In vitro studies have shown that these particles can be continuously imaged by US up to 48 min and their signal lifetime persisted for 5 days. These particles could potentially be given by intravenous injection and, in conjunction with contrast-enhanced ultrasound, be utilized as a screening tool to detect smaller breast cancers before they are detectible by traditional mammography.

SUBMITTER: Liberman A

PROVIDER: S-EPMC3588157 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors.

Liberman Alexander A Martinez H Paul HP Ta Casey N CN Barback Christopher V CV Mattrey Robert F RF Kono Yuko Y Blair Sarah L SL Trogler William C WC Kummel Andrew C AC Wu Zhe Z

Biomaterials 20120411 20

Diagnosing tumors at an early stage when they are easily curable and may not require systemic chemotherapy remains a challenge to clinicians. In order to improve early cancer detection, gas filled hollow boron-doped silica particles have been developed, which can be used for ultrasound-guided breast conservation therapy. The particles are synthesized using a polystyrene template and subsequently calcinated to create hollow, rigid nanoporous microspheres. The microshells are filled with perfluoro ...[more]

PMID: 22498299

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Project description:BackgroundThe aim of modern medicine is to safely classify diseases for successful therapy without invasive measures. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) are potent imaging techniques. However, without contrast medium, the informative value of the 3 native methods is limited. The advantages of sonography are: no radiation exposure or previously known physically harmful interactions with tissue, proportionate disappearance of a contrast agent risk, no (probably irreversible) contrast agent deposits, and no risk of renal insufficiency. But, is that enough to compete with of even exceed CT and MRI?SummaryIn this review, the state of the art of contrast-enhanced ultrasound (CEUS) in the abdominal cavity is presented. The remarkable diagnostic possibilities can unfortunately only be demonstrated here in a small number of impressive, typical case studies underpinned by the literature, so that, from one's own perspective, the full spectrum of CEUS can be used by oneself or initiated. Within the limits of physics, the real-time dynamics of CEUS enable conclusions to be drawn, so that with the current technology, sonography, including expansion by contrast, can be considered superior to other imaging methods. It is not uncommon for CEUS to have the value of a control and reference method.Key messagesSonography very often enables reliable diagnostics. The introduction of a contrast agent in sonography has led to a quantum leap similar to that of other imaging techniques. Already natively, the real-time representation of dynamic events leads to a certain superiority, i.e., complete observation of the inflow and outflow phases of the contrast medium and the resulting diagnostic; tissue-specific differentiation options provide a unique selling point. Further advantages of the first-choice imaging diagnostic method are: a lack of radiation exposure, repeatability of the examination at any time, local independence, a negligible allergy rate compared to the contrast agents of other methods, and a lack of kidney and thyroid exposure or excluded deposits.

Project description:The biological response of normal tissue to high-dose radiation treatment remains poorly understood. Alterations to the microenvironment, specifically the microvasculature, have been implicated as a significant contributor to tumoral cytotoxicity. We used contrast-enhanced ultrasound (CEU) perfusion imaging, which is uniquely suited to assess functional status of the microcirculation, to measure microvascular blood flow after high-dose irradiation to normal skeletal muscle tissue in a murine model. Proximal hindlimbs of wild-type C57Bl/6 mice were irradiated with a single fraction using 6 MV photons, 1 cm bolus and a dynamic wedge. Quantitative perfusion CEU imaging of the skeletal muscle was performed at days 1 and 8 postirradiation in three different regions of interest (ROIs): 1. 15 Gy external-beam irradiated leg; 2. 12 Gy irradiated 5 mm proximal area; 3. single ROI in the nonirradiated contralateral (CL) hindlimb. Perfusion imaging was also performed in the hindlimb of nonirradiated mice. CEU time-intensity data were analyzed to measure microvascular blood flow (MBF, also referred to as perfusion), and its parametric components of microvascular flux rate and functional microvascular blood volume (MBV). Plasma measurements of two potent vasoconstrictors, endothelin-1 and angiotensin II, were also performed to assess systemic response. CEU perfusion imaging values for the 12 and 15 Gy irradiated limb regions were pooled. At day 1, MBF in the irradiated limb was significantly lower than in the CL limb (P = 0.016) but quite similar to the nonirradiated mice. At day 8, both limbs of irradiated mice exhibited a trend towards lower MBF than the limbs of nonirradiated mice (28% decrease in mean MBF, P = 0.149 for CL; 39% decrease, P = 0.065 for irradiated limb). Compared to nonirradiated animals, the reduction in perfusion in irradiated limbs at day 8 may have been more influenced by the microvascular flux rate (25% decrease in the mean, P = 0.079) than the MBV (12% decrease in the mean, P = 0.328). Examination of vasoactive compounds revealed that the average plasma concentration for endothelin-1 at day 8 postirradiation was significantly higher in 14 irradiated animals than in 4 nonirradiated animals (3.07 pg/ ml vs. 2.51 pg/ml; P = 0.011). Up to day 8 after high-dose irradiation, flow deficits in irradiated muscle appear to be a consequence of increased vascular resistance more so than loss or functional de-recruitment of microvascular units.

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Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors.

Publications

Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors.

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