Huizhong Cui

Growth of melanoma brain tumors monitored by photoacoustic microscopy

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Ultrathin gold nanowire-functionalized carbon nanotubes for hybrid molecular sensing.

Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical field effect transistor and optical sensors, because of their extraordinary one-dimensional electronic structure, thermal conductivity, and tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that noncovalent ultrathin gold nanowires functionalized multiwalled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the alpha-fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal, and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing, and treatment functionalities.

Photoacoustic contrast imaging of biological tissues with nanodiamonds fabricated for high near-infrared absorbance

Abstract. Radiation-damaged nanodiamonds (DNDs) are potentially ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their low toxicity and high optical absorbance. PA imaging contrast agents have been limited to quantum dots and gold particles, since most existing carbon-based nanoparticles, including fluorescent nanodiamonds, do not have sufficient optical absorption in the near-infrared (NIR) range. A new DND by He+ ion beam irradiation with very high NIR absorption was synthesized. These DNDs produced a 71-fold higher PA signal on a molar basis than similarly dimensioned gold nanorods, and 7.1 fmol of DNDs injected into rodents could be clearly imaged 3 mm below the skin surface with PA signal enhancement of 567% using an 820-nm laser wavelength.

Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer

The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.

Integration of photoacoustic imaging and high-intensity focused ultrasound

We have developed an integrated photoacoustic imaging (PAI) and high-intensity focused ultrasound (HIFU) system for solid tumor treatments. A single-element, spherically focused ultrasonic transducer, with a central frequency of 5 MHz, was used to induce HIFU lesions in soft tissue. The same ultrasonic transducer was also used as a detector during PAI to guide HIFU ablation. The use of same transducer for PAI and HIFU can reduce the requirement on acoustic windows during the imaging-guided therapy, as well as ensuring the correct alignment between the therapeutic beam and the planned treatment volume. During an experiment, targeted soft tissue was first imaged by PAI. The resulted image was used to plan the subsequent HIFU ablation. After the HIFU ablation, targeted soft tissue was imaged again by PAI to evaluate the effectiveness of treatments. Good contrast was obtained between photoacoustic images before and after HIFU ablation. In conclusion, our results demonstrated that PAI technology may potentially be integrated with HIFU ablation for image-guided therapy.

Laser-enhanced cavitation during high intensity focused ultrasound: An in vivo study

Laser-enhanced cavitation during high intensity focused ultrasound (HIFU) was studied in vivo using a small animal model. Laser light was employed to illuminate the sample concurrently with HIFU radiation. The resulting cavitation was detected with a passive cavitation detector. The in vivo measurements were made under different combinations of HIFU treatment depths, laser wavelengths, and HIFU durations. The results demonstrated that concurrent light illumination during HIFU has the potential to enhance cavitation effect by reducing cavitation threshold in vivo.

In vivo photoacoustic imaging of chemotherapy-induced apoptosis in squamous cell carcinoma using a near-infrared caspase-9 probe

Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells. However, no tools exist in the clinic for detecting apoptosis in real time. Microscopic examination of surgical biopsies and secondary responses, such as morphological changes, are used to verify efficacy of a treatment. Here, we developed a novel near-infrared dye-based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a noninvasive photoacoustic imaging (PAI) technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy (10 mg/kg) and were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.

Synthesis and characterization of rare-earth-free magnetic manganese bismuth nanocrystals

Earth abundant manganese bismuth (MnBi) has long been of interest due to its large magnetocrystalline anisotropy and high energy density for advanced permanent magnet applications. However, solution synthesis of MnBi phase is challenging due to the reduction potential mismatch between Mn and Bi elements. In this study, we show a versatile MnBi synthesis method involving the metal co-reduction followed by thermal annealing. The magnetically hard MnBi crystalline phase is then exchange coupled with magnetically soft cobalt coating. Our processing approach offers a promising strategy for manufacturing rare-earth-free magnetic nanocrystals.

Iron sulfide ink for the growth of pyrite crystals

Iron pyrite (FeS2, Fools Gold) is a non-toxic, earth abundant semiconductor that exhibits promise for use in energy conversion and storage devices, such as the cathode material for batteries, thermoelectrics and optoelectronics. However, pyrites potential as an energy-critical material is being curbed due to problems with controlling composition, stoichiometry and bulk and surface defects. To overcome these problems, simple and scalable methods to grow high quality crystalline pyrite for in-depth studies are necessary. In this study, we report a facile approach to create high quality, micron sized pyrite crystals from the FeS wire molecular ink. Growth of high quality pyrite crystals is examined and a model for growth and surface facet dependent activation energy is proposed. Unique thermal measurements are preformed that allow for insight into the pyrites crystallinity and thermoconductive properties. It is shown that as made pyrite crystals exhibit high crystallinity which will be vital for future in-depth studies and device fabrication.

In vivo photoacoustic imaging of breast cancer tumor with HER2-targeted nanodiamonds

Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.