Publications by authors named "Shengping Qin"

Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250 kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuation compared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents).

View Article and Find Full Text PDF

(89)Zr (t1/2=78.4h), a positron-emitting metal, has been exploited for PET studies of antibodies because of its relatively long decay time and facile labeling procedures. Here, we used (89)Zr to evaluate the pharmacokinetics of long-circulating liposomes over 168h (1week).

View Article and Find Full Text PDF

Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases.

View Article and Find Full Text PDF

Our goal is to provide a physiological perspective on the use of imaging to optimize and monitor the accumulation of nanotherapeutics within target tissues, with an emphasis on evaluating the pharmacokinetics of organic particles. Positron emission tomography (PET), magnetic resonance imaging (MRI) and ultrasound technologies, as well as methods to label nanotherapeutic constructs, have created tremendous opportunities for preclinical optimization of therapeutics and for personalized treatments in challenging disease states. Within the methodology summarized here, the accumulation of the construct is estimated directly from the image intensity.

View Article and Find Full Text PDF

Acquisition of the epithelial-mesenchymal transition (EMT) tumor phenotype is associated with impaired chemotherapeutic delivery and a poor prognosis. In this study, we investigated the application of therapeutic ultrasound methods available in the clinic to increase nanotherapeutic particle accumulation in epithelial and EMT tumors by labeling particles with a positron emission tomography tracer. Epithelial tumors were highly vascularized with tight cell-cell junctions, compared with EMT tumors where cells displayed an irregular, elongated shape with loosened cell-cell adhesions and a reduction in E-cadherin and cytokeratins 8/18 and 19.

View Article and Find Full Text PDF

Therapeutic ultrasound (US) can be noninvasively focused to activate drugs, ablate tumors and deliver drugs beyond the blood brain barrier. However, well-controlled guidance of US therapy requires fusion with a navigational modality, such as magnetic resonance imaging (MRI) or X-ray computed tomography (CT). Here, we developed and validated tissue characterization using a fusion between US and CT.

View Article and Find Full Text PDF

As the applications of ultrasonic thermal therapies expand, the design of the high-intensity array must address both the energy delivery of the main beam and the character and relevance of off-target beam energy. We simulate the acoustic field performance of a selected set of circular arrays organized by array format, including flat versus curved arrays, periodic versus random arrays, and center void diameter variations. Performance metrics are based on the -3-dB focal main lobe (FML) positioning range, axial grating lobe (AGL) temperatures, and side lobe levels.

View Article and Find Full Text PDF

Changes in lipid acyl chain length can result in desorption of lipid from the liposomal anchorage and interaction with blood components. PET studies of the stability of such lipids have not been performed previously although such studies can map the pharmacokinetics of unstable lipids non-invasively in vivo. The purpose of this study was to characterize the in vivo clearance of (64)Cu-labeled distearoyl- and dipalmitoyl lipid included within long circulating liposomes.

View Article and Find Full Text PDF

Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease.

Experimental Design: Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ.

View Article and Find Full Text PDF

The Rayleigh-Plesset (RP) equation for a clean gas bubble in an incompressible and infinite liquid has previously been applied to approximately simulate the behavior of ultrasound contrast agents (UCA) in vivo, and extended RP equations have been proposed to account for the effects of the UCA shell or surrounding soft tissue. These models produce results that are consistent with experimental measurements for low acoustic pressure scenarios. For applications of UCAs in therapeutic medicine, the transmitted acoustic pulse can have a peak negative pressure (PNP) up to a few megapascals, resulting in discrepancies between measurements and predictions using these extended RP equations.

View Article and Find Full Text PDF

When microbubble contrast agents are driven by ultrasound, the transport of drugs and particles across cell membranes and blood vessel walls is enhanced. While a wide range of acoustic parameters enhance delivery, the acoustic parameters that maximize delivery while simultaneously minimizing biological effects have not been fully characterized. Here, we use a gel phantom with a Young's modulus similar to that of tissue to directly observe bubble interaction with the gel surface during insonation.

View Article and Find Full Text PDF

To provide a continuous and prolonged delivery of the substrate D-luciferin for bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using either the pH gradient or acetate gradient method. Under optimum loading conditions, 0.17 mg luciferin was loaded per mg of lipid with 90-95% encapsulation efficiency, where active loading was 6 to 18-fold higher than that obtained with passive loading.

View Article and Find Full Text PDF

Simultaneous labeling of the drug compartment and shell of delivery vehicles with optical and positron emission tomography (PET) probes is developed and employed to inform a hybrid physiologically based pharmacokinetic model. Based on time-dependent estimates of the concentration of these tracers within the blood pool, reticuloendothelial system (RES) and tumor interstitium, we compare the stability and circulation of long-circulating and temperature-sensitive liposomes. We find that rates of transport to the RES for long-circulating and temperature-sensitive particles are 0.

View Article and Find Full Text PDF

Insonified microbubbles were observed in vessels within a gel with a Young's modulus similar to that of tissue, demonstrating shape instabilities, liquid jets, and the formation of small tunnels. In this study, tunnel formulation occurred in the direction of the propagating ultrasound wave, where radiation pressure directed the contact of the bubble and gel, facilitating the activity of the liquid jets. Combinations of ultrasonic parameters and microbubble concentrations that are relevant for diagnostic imaging and drug delivery and that lead to tunnel formation were applied and the resulting tunnel formation was quantified.

View Article and Find Full Text PDF

Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies.

View Article and Find Full Text PDF

Silica, cellulose and polymethylmethacrylate tubes with inner diameters of ten to a few hundred microns are commonly used as blood vessel phantoms in in vitro studies of microbubble or nanodroplet behavior during insonation. However, a detailed investigation of the ultrasonic fields within these micro-tubes has not yet been performed. This work provides a theoretical analysis of the ultrasonic fields within micro-tubes.

View Article and Find Full Text PDF

The use of ultrasound radiation force to manipulate microbubbles in blood vessels has attracted recent interest as a method to increase the efficiency of ultrasonic molecular imaging and drug delivery. However, recent studies indicate that microbubble oscillation is diminished within small blood vessels, and therefore we investigate microbubble oscillation and translation within 12 microm vessels using high-speed photography. With each 0.

View Article and Find Full Text PDF

Many thousands of contrast ultrasound studies have been conducted in clinics around the world. In addition, the microbubbles employed in these examinations are being widely investigated to deliver drugs and genes. Here, for the first time, the oscillation of these microbubbles in small vessels is directly observed and shown to be substantially different than that predicted by previous models and imaged within large fluid volumes.

View Article and Find Full Text PDF

Ultrasound contrast agents (UCAs) are under intensive investigation for their applications in physiological and molecular imaging and drug delivery. Prediction of the natural frequency of the oscillation of UCAs in microvessels has drawn increasing attention. To our knowledge, the existing models to predict the natural frequency of oscillation of UCAs in microvessels all apply the linear approximation and treat the blood vessel wall as a rigid boundary.

View Article and Find Full Text PDF

Purpose: To characterize the effect of low-frequency contrast material-enhanced ultrasound on the vascular endothelium and to determine the parameters and techniques required to deliver a therapeutic agent by using the chorioallantoic membrane (CAM) model.

Materials And Methods: All in vivo animal procedures were conducted with institutional Animal Care and Use Committee approval. Extravasation of 8.

View Article and Find Full Text PDF

The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site.

View Article and Find Full Text PDF

This paper presents a detailed study of the oscillation characteristics of a bubble confined inside a deformable microvessel, whose size is comparable with the bubble size. The vessel's compliance is characterized by a nonlinear relation between the intraluminal pressure and the expansion ratio of the vessel radius, which represents the variation of the vessel stiffness with the pressure of the filling liquid. In this analysis, an initially spherical bubble evolves into an ellipsoid, and the asymmetric oscillation appears immediately after the driving pressure is applied and magnifies with oscillation cycles.

View Article and Find Full Text PDF

Objective: To investigate clinical characteristics and rational surgical therapy for cardiac cancer patients over 70 years.

Methods: From 1991 to 2003, clinical data of 206 patients with advanced cardiac cancer were collected and analyzed. The patients were divided into two groups as the group of patients over 70 years old (103 cases) and the group younger than 70 years old (100 cases).

View Article and Find Full Text PDF

This work examines the characteristic differences in acoustic scattering between air-filled double-layered encapsulating (DLE) shells and air-filled single-layered encapsulating (SLE) shells. The analysis shows that the presence of an outer layer softer than the inner layer results in a shift of the first monopole of the reflectivity-frequency response to a higher frequency and a reduction in the monopole peak; and it leads to a frequency-separation of the two dipoles that trace the monopole. The frequency shift and the peak reduction of the monopole and the frequency separation of the two dipoles all increase with the increasing thickness of the softer outer layer.

View Article and Find Full Text PDF