Photoacoustic tomography (PAT) has emerged as a hybrid, nonionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. Here, we demonstrate the application of a novel organic PAT contrast agent based on polypyrrole nanoparticles (PPy NPs). Monodisperse PPy NPs are ∼46 nm in diameter with strong absorption in the near-infrared (NIR) range, which allowed visualization of PPy NP-containing agar gel embedded in chicken breast muscle at a depth of ∼4.3 cm. Compared with PAT images based on the intrinsic optical contrast in mice, the PAT images acquired within 1 h after intravenous administration of PPy NPs showed the brain vasculature with greater clarity than hemoglobin in blood. Preliminary results showed no acute toxicity to the vital organs (heart, liver, spleen, lungs and kidneys) in mice following a single imaging dose of PPy NPs. Our results indicate that PPy NPs are promising contrast agents for PAT with good biocompatibility, high spatial resolution and enhanced sensitivity.
A Pilot Studyonoelastography is now routinely used in medical sonography since Ophir et al 1 first described the principles of strain imaging in 1991. The technique can assess the elastic properties of tissues, and static elastography has found clinical application in diagnosing lesions of the breast, 2 thyroid, 3 lymph nodes, 4 and prostate gland. 5 The basic principle of sonoelastography is to produce displacement within the tissue by physical compression. By comparing the images taken before and after the application of compression, sonoelastography can show different degrees of displacement. 1 However, the stiffness of the tissue can only be obtained by comparing it with surrounding normal tissues. The degree of the compression applied by the operator may alter the results of sonoelastography. -Mei Chen, MD, PhD, Li-Gang Cui, MD, PhD, Ping He, MD, PhD, Wei-Wei Shen, MD, MS, Ya-Jun Qian, MD, MS, Jin-Rui Wang, MD, BS Received June 4, 2012, Xiang ORIGINAL RESEARCHObjectives-The purpose of this study was to investigate the feasibility of using quantitative shear wave elastography for assessing the functional integrity of the Achilles tendon and to summarize the changes in elasticity of ruptured Achilles tendons in comparison with normal controls.Methods-Thirty-six normal and 14 ruptured Achilles tendons were examined with shear wave elastography coupled with a linear array transducer (4-15 MHz). The elasticity value of each Achilles tendon in a longitudinal view was measured.Results-The mean elasticity value ± SD for the normal Achilles tendons was 291.91 ± 4.38 kPa (note that there are saturated measurement phenomena for the normal Achilles tendon, so the actual value will be >300 kPa), whereas the ruptured Achilles tendons had an elasticity value of 56.48 ± 68.59 kPa. A statistically significant difference was found in relation to the findings in healthy volunteers (P = .006).Conclusions-Our results suggest that shear wave elastography is a valuable tool that can provide complementary biomechanical information for evaluating the function of the Achilles tendon.
Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.
Multidrug resistance remains one of the main obstacles to efficient chemotherapy of colorectal cancer. Herein, an efficient combination therapeutic strategy is proposed based on porphyrin/camptothecin-floxuridine triad microbubbles (PCF-MBs) with high drug loading contents, which own highly stable co-delivery drug combinations and no premature release. The triad PCF-MBs can act not only as a contrast agent for ultrasound (US)/fluorescence bimodal imaging but also a multimodal therapeutic agent for synergistic chemo-photodynamic combination therapy. Upon local ultrasound exposure under the guidance of ultrasound imaging, in situ conversion of PCF-MBs into porphyrin/camptothecin-floxuridine nanoparticles (PCF-NPs) leads to high accumulation of chemo-drugs and photosensitizer in tumors due to the induced high permeability of the capillary wall and cell membrane temporarily via sonoporation effect, greatly reducing the risk of systemic exposure. Most importantly, it was found that the PCF-MB-mediated photodynamic therapy could significantly reduce the expression of adenosine-triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG), which is responsible for the drug resistance in chemotherapy, resulting in a prominent intracellular camptothecin increase. In vivo experiments revealed that the PCF-MBs in combination with ultrasound and laser irradiation could achieve a 90% tumor inhibition rate of HT-29 cancer with no recurrence. Therefore, such triad PCF-MB-based combination therapeutic strategy shows great promise for overcoming drug resistance of colorectal cancer and other cancers.
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