Jin Ho Chang

Amplified Photoacoustic Performance and Enhanced Photothermal Stability of Reduced Graphene Oxide Coated Gold Nanorods for Sensitive Photoacoustic Imaging

We report a strongly amplified photoacoustic (PA) performance of the new functional hybrid material composed of reduced graphene oxide and gold nanorods. Due to the excellent NIR light absorption properties of the reduced graphene oxide coated gold nanorods (r-GO-AuNRs) and highly efficient heat transfer process through the reduced graphene oxide layer, r-GO-AuNRs exhibit excellent photothermal stability and significantly higher photoacoustic amplitudes than those of bare-AuNRs, nonreduced graphene oxide coated AuNRs (GO-AuNRs), or silica-coated AuNR, as demonstrated in both in vitro and in vivo systems. The linear response of PA amplitude from reduced state controlled GO on AuNR indicates the critical role of GO for a strong photothermal effect of r-GO-AuNRs. Theoretical studies with finite-element-method lab-based simulation reveal that a 4 times higher magnitude of the enhanced electromagnetic field around r-GO-AuNRs can be generated compared with bare AuNRs or GO-AuNRs. Furthermore, the r-GO-AuNRs are expected to be a promising deep-tissue imaging probe because of extraordinarily high PA amplitudes in the 4-11 MHz operating frequency of an ultrasound transducer. Therefore, the r-GO-AuNRs can be a useful imaging probe for highly sensitive photoacoustic images and NIR sensitive therapeutics based on a strong photothermal effect.

Enhancement of photoacoustic image quality by sound speed correction: ex vivo evaluation

Real-time photoacoustic (PA) imaging involves beamforming methods using an assumed fixed sound speed, typically 1540 m/s in soft tissue. This leads to degradation of PA image quality because the true sound speed changes as PA signal propagates through different types of soft tissues: the range from 1450 m/s to 1600 m/s. This paper proposes a new method for estimating an optimal sound speed to enhance the cross-sectional PA image quality. The optimal sound speed is determined when coherent factor with the sound speed is maximized. The proposed method was validated through simulation and ex vivo experiments with microcalcification-contained breast cancer specimen. The experimental results demonstrated that the best lateral resolution of PA images of microcalcifications can be achieved when the optimal sound speed is utilized.

A Novel Envelope Detector for High-Frame Rate, High-Frequency Ultrasound Imaging

This paper proposes a novel design of envelope detectors capable of supporting a small animal cardiac imaging system requiring a temporal resolution of more than 150 frames per second. The proposed envelope detector adopts the quadrature demodulation and the look-up table (LUT) method to compute the magnitude of the complex baseband components of received echo signals. Because the direct use of the LUT method for a square root function is not feasible due to a large memory size, this paper presents a new LUT strategy dramatically reducing its size by using binary logarithmic number system (BLNS). Due to the nature of BLNS, the proposed design does not require an individual LOG-compression functional block. In the implementation using a field programmable gate array (FPGA), a total of 166.56 Kbytes memories were used for computing the magnitude of 16-bit in-phase and quadrature components instead of 4 Gbytes in the case of the direct use of the LUT method. The experimental results show that the proposed envelope detector is capable of generating LOG- compressed envelope data at every clock cycle after 32 clock cycle latency, and its maximum error is less than 0.5 (i.e., within the rounding error), compared with the arithmetic results of square root function and LOG compression.

Optimal laser wavelength for photoacoustic imaging of breast microcalcifications

This paper presents photoacoustic imaging (PAI) for real-time detection of micro-scale calcifications (e.g., <1 mm) in the breast, which are an indicator of the cancer occurrence. Optimal wavelength of incident laser for the microcalcification imaging was ascertained through ex vivo experiments with seven breast specimens of volunteers. In the ex vivo experiments, the maximum amplitude of photoacoustic signals from the microcalcifications occurred when the laser wavelength ranged from 690 to 700 nm. This result demonstrated that PAI can serve as a real-time imaging and guidance tool for diagnosis and biopsy of the breast microcalcifications.

20 MHz/40 MHz dual element transducers for high frequency harmonic imaging

Concentric annular type dual element transducers for second harmonic imaging at 20 MHz / 40 MHz were designed and fabricated to improve spatial resolution and depth of penetration for ophthalmic imaging applications. The outer ring element was designed to transmit the 20 MHz signal and the inner circular element was designed to receive the 40 MHz second harmonic signal. Lithium niobate (LiNbO3), with its low dielectric constant, was used as the piezoelectric material to achieve good electrical impedance matching. Double matching layers and conductive backing were used and optimized by KLM modeling to achieve high sensitivity and wide bandwidth for harmonic imaging and superior time-domain characteristics. Prototype transducers were fabricated and evaluated quantitatively and clinically. The average measured center frequency for the transmit ring element was 21 MHz and the one-way -3 dB bandwidth was greater than 50%. The 40 MHz receive element functioned at 31 MHz center frequency with acceptable bandwidth to receive attenuated and frequency downshifted harmonic signal. The lateral beam profile for the 20 MHz ring elements at the focus matched the Field II simulated results well, and the effect of outer ring diameter was also examined. Images of a posterior segment of an excised pig eye and a choroidal nevus of human eye were obtained both for single element and dual element transducers and compared to demonstrate the advantages of dual element harmonic imaging.

Photoacoustic imaging of breast microcalcifications: A validation study with 3-dimensional ex vivo data and spectrophotometric measurement

Breast microcalcification has been served as an important early-indicator of breast cancer. In the conventional screening procedure for the breast cancer, X-ray mammography is first conducted and the malignancy of the suspicious patient is confirmed by conducting needle biopsy with real-time imaging-assisted guidance, i.e., stereotactic and US imaging. However, these biopsy guidance methods suffer from large amount of radiative exposure and limited sensitivity on microcalcifications without a mass, respectively. In this paper, we verify the capability of photoacoustic imaging (PAI) for detection of the breast microcalcifications by comparing their locations in a 3-D PA image with those in the corresponding X-ray mammography. For this, cross-sectional PA/US images of breast ex vivo specimens were sequentially acquired with 7.2-MHz linear array transducer and the procedure was repeated by moving the transducer along the elevation direction at an increment of 0.3 mm. A Surelite Nd:YAG OPO system (Continuum Inc., USA) was used for the laser excitation at the rate of 10 Hz with a bifurcated optical fiber bundle for laser delivery. PA signals generated in the specimen were captured with SonixTouch research package (Ultrasonix Corp., Canada). With a volume-rendered PA/US image, it is shown that the locations of the microcalcifications in the X-ray mammography meshed well with those in PA images. From the experimental results, therefore, it is demonstrates that PAI can be an effective alternative for noninvasive, real-time biopsy guidance for breast cancer screening.

Formation of Semimetallic Cobalt Telluride Nanotube Film via Anion Exchange Tellurization Strategy in Aqueous Solution for Electrocatalytic Applications

Metal telluride nanostructures have demonstrated several potential applications particularly in harvesting and storing green energy. Metal tellurides are synthesized by tellurization process performed basically at high temperature in reducing gas atmosphere, which makes the process expensive and complicated. The development of a facile and economical process for desirable metal telluride nanostructures without complicated manipulation is still a challenge. In an effort to develop an alternative strategy of tellurization, herein we report a thin film formation of self-standing cobalt telluride nanotubes on various conducting and nonconducting substrates using a simple binder-free synthetic strategy based on anion exchange transformation from a thin film of cobalt hydroxycarbonate nanostructures in aqueous solution at room temperature. The nanostructured films before and after ion exchange transformation reaction are characterized using field emission scanning electron microscope, energy dispersive X-ray analyzer, X-ray photoelectron spectroscopy, thin film X-ray diffraction technique, high resolution transmission electron microscope, and selected area electron diffraction analysis technique. After the ion exchange transformation of nanostructures, the film shows conversion from insulator to highly electrical conductive semimetallic characteristic. When used as a counter electrode in I3(-)/I(-) redox electrolyte based dye-sensitized solar cells, the telluride film exhibits an electrocatalytic reduction activity for I3(-) with a demonstration of solar-light to electrical power conversion efficiency of 8.10%, which is highly competitive to the efficiency of 8.20% exhibited by a benchmarked Pt-film counter electrode. On the other hand, the telluride film electrode also demonstrates electrocatalytic activity for oxygen evolution reaction from oxidation of water.

Ultrasound transducer and system for real-time simultaneous therapy and diagnosis for noninvasive surgery of prostate tissue

For noninvasive treatment of prostate tissue using high-intensity focused ultrasound this paper proposes a design of an integrated multifunctional confocal phased array (IMCPA) and a strategy to perform both imaging and therapy simultaneously with this array. IMCPA is composed of triplerow phased arrays: a 6-MHz array in the center row for imaging and two 4-MHz arrays in the outer rows for therapy. Different types of piezoelectric materials and stack configurations may be employed to maximize their respective functionalities, i.e., therapy and imaging. Fabrication complexity of IMCPA may be reduced by assembling already constructed arrays. In IMCPA, reflected therapeutic signals may corrupt the quality of imaging signals received by the center-row array. This problem can be overcome by implementing a coded excitation approach and/or a notch filter when B-mode images are formed during therapy. The 13-bit Barker code, which is a binary code with unique autocorrelation properties, is preferred for implementing coded excitation, although other codes may also be used. From both Field II simulation and experimental results, we verified whether these remedial approaches would make it feasible to simultaneously carry out imaging and therapy by IMCPA. The results showed that the 13-bit Barker code with 3 cycles per bit provided acceptable performances. The measured -6 dB and -20 dB range mainlobe widths were 0.52 mm and 0.91 mm, respectively, and a range sidelobe level was measured to be -48 dB regardless of whether a notch filter was used. The 13-bit Barker code with 2 cycles per bit yielded -6 dB and -20 dB range mainlobe widths of 0.39 mm and 0.67 mm. Its range sidelobe level was found to be -40 dB after notch filtering. These results indicate the feasibility of the proposed transducer design and system for real-time imaging during therapy.

Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy.

Biomedical imaging-guided cancer therapy should have capabilities of both accurate tumor diagnosis and high therapeutic efficacy for the personalized treatment. Various biomedical imaging-guided cancer therapies are currently being investigated to overcome current limitations that include low sensitivity of diagnosis and poor drug delivery to the tumor site. Here, we report the development of a multifunctional theranostic contrast agent demonstrating high sensitive photoacoustic and ultrasound imaging and effective local delivery of anticancer drug to a tumor site. A microbubble (porphyrin-MB) was developed using phospholipid-porphyrin conjugates to enhance ultrasound and photoacoustic signal intensities simultaneously. Paclitaxel-loaded human serum albumin nanoparticles (PTX-HSA-NPs) were then conjugated onto the surface of the microbubble. The developed PTX-HSA-NPs conjugated porphyrin-MB (porphyrin-MB-NPs) provided sensitive, dual modal images of a tumor at 700 nm optimal laser wavelength for photoacoustic imaging and 5-14 MHz operating frequency for the ultrasound imaging. In addition, porphyrin-MB-NPs efficiently suppressed tumor growth by ultrasound exposure. Exposure to the focused ultrasound triggered the collapse of porphyrin-MB-NPs, resulting in the local release of PTX-HSA-NPs and enhanced penetration into the tumor site. The increased preferential accumulation and penetration of PTX-HSA-NPs suppressed tumor growth 10-fold more than without exposure to ultrasound. In conclusion, the developed porphyrin-MB-NPs establish a new paradigm in simultaneous bi-functional ultrasound/photoacoustic imaging diagnosis and locally triggered release of nanomedicine and enhanced chemotherapy efficiency.

In vitro estimation of mean sound speed based on minimum average phase variance in medical ultrasound imaging

Effective receive beamforming in medical ultrasound imaging is important for enhancing spatial and contrast resolution. In current ultrasound receive beamforming, a constant sound speed (e.g., 1540m/s) is assumed. However, the variations of sound speed in soft tissues could introduce phase distortions, leading to degradation in spatial and contrast resolution. This degradation becomes even more severe in imaging fatty tissues (e.g., breast) and with obese patients. In this paper, a mean sound speed estimation method where phase variance of radio-frequency channel data in the region of interest is evaluated is presented for improving spatial and contrast resolution. The proposed estimation method was validated by the Field II simulation and the tissue mimicking phantom experiments. In the simulation, the sound speed of the medium was set to 1450m/s and the proposed method was capable of capturing this value correctly. From the phantom experiments, the -18-dB lateral resolution of the point target at 50mm obtained with the estimated mean sound speed was improved by a factor of 1.3, i.e., from 3.9mm to 2.9mm. The proposed estimation method also provides an improvement of 0.4 in the contrast-to-noise ratio, i.e., from 2.4 to 2.8. These results indicate that the proposed mean sound speed estimation method could enhance the spatial and contrast resolution in the medical ultrasound imaging systems.