Changho Lee

Au-Cu2- xSe heterodimer nanoparticles with broad localized surface plasmon resonance as contrast agents for deep tissue imaging

We report a new type of heterogeneous nanoparticles (NPs) composed of a heavily doped semiconductor domain (Cu2-xSe) and a metal domain (Au), which exhibit a broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. We demonstrate both in vivo photoacoustic imaging and in vitro dark field imaging, using the broad LSPR in Cu2-xSe-Au hybrid NPs to achieve contrast at different wavelengths. The high photoacoustic imaging depth achieved, up to 17 mm, shows that these novel contrast agents could be clinically relevant. More broadly, this work demonstrates a new strategy for tuning LSPR absorbance by engineering the density of free charge carriers in two interacting domains.

Full-range k-domain linearization in spectral-domain optical coherence tomography

A full-bandwidth k-domain linearization method for spectral-domain optical coherence tomography (SD-OCT) is demonstrated. The method uses information of the wavenumber-pixel-position provided by a translating-slit-based wavelength filter. For calibration purposes, the filter is placed either after a broadband source or at the end of the sample path, and the filtered spectrum with a narrowed line width (∼0.5u2009nm) is incident on a line-scan camera in the detection path. The wavelength-swept spectra are co-registered with the pixel positions according to their central wavelengths, which can be automatically measured with an optical spectrum analyzer. For imaging, the method does not require a filter or a software recalibration algorithm; it simply resamples the OCT signal from the detector array without employing rescaling or interpolation methods. The accuracy of k-linearization is maximized by increasing the k-linearization order, which is known to be a crucial parameter for maintaining a narrow point-spread function (PSF) width at increasing depths. The broadening effect is studied by changing the k-linearization order by undersampling to search for the optimal value. The system provides more position information, surpassing the optimum without compromising the imaging speed. The proposed full-range k-domain linearization method can be applied to SD-OCT systems to simplify their hardware/software, increase their speed, and improve the axial image resolution. The experimentally measured width of PSF in air has an FWHM of 8u2009μm at the edge of the axial measurement range. At an imaging depth of 2.5u2009mm, the sensitivity of the full-range calibration case drops less than 10u2009dB compared with the uncompensated case.

Optical Sensing Method for Screening Disease in Melon Seeds by Using Optical Coherence Tomography

We report a noble optical sensing method to diagnose seed abnormalities using optical coherence tomography (OCT). Melon seeds infected with Cucumber green mottle mosaic virus (CGMMV) were scanned by OCT. The cross-sectional sensed area of the abnormal seeds showed an additional subsurface layer under the surface which is not found in normal seeds. The presence of CGMMV in the sample was examined by a blind test (n = 140) and compared by the reverse transcription-polymerase chain reaction. The abnormal layers (n = 40) were quantitatively investigated using A-scan sensing analysis and statistical method. By utilizing 3D OCT image reconstruction, we confirmed the distinctive layers on the whole seeds. These results show that OCT with the proposed data processing method can systemically pick up morphological modification induced by viral infection in seeds, and, furthermore, OCT can play an important role in automatic screening of viral infections in seeds.

Combined photoacoustic and optical coherence tomography using a single near-infrared supercontinuum laser source

We developed an integrated dual-modal photoacoustic and optical coherence tomography (PA-OCT) system using a single near-infrared supercontinuum laser source to simultaneously provide both optical absorption and scattering contrasts. A pulsed broadband supercontinuum source was generated by a pulsed Nd:YAG laser and a photonic-crystal fiber. When we imaged two colored hairs, the black hair was visible in both PA and OCT images, whereas the white hair was only mapped in the OCT image. The single laser source will potentially allow us to implement relatively simple, cheap, and compact dual-modal PA-OCT systems, which are key criteria for fast clinical translation and commercialization.

Ultra-fast displaying Spectral Domain Optical Doppler Tomography system using a Graphics Processing Unit.

We demonstrate an ultrafast displaying Spectral Domain Optical Doppler Tomography system using Graphics Processing Unit (GPU) computing. The calculation of FFT and the Doppler frequency shift is accelerated by the GPU. Our system can display processed OCT and ODT images simultaneously in real time at 120 fps for 1,024 pixels × 512 lateral A-scans. The computing time for the Doppler information was dependent on the size of the moving average window, but with a window size of 32 pixels the ODT computation time is only 8.3 ms, which is comparable to the data acquisition time. Also the phase noise decreases significantly with the window size. Since the performance of a real-time display for OCT/ODT is very important for clinical applications that need immediate diagnosis for screening or biopsy. Intraoperative surgery can take much benefit from the real-time display flow rate information from the technology. Moreover, the GPU is an attractive tool for clinical and commercial systems for functional OCT features as well.

Biodegradable Photonic Melanoidin for Theranostic Applications

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that generally regarded as safe (GRAS) melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

Biodegradable Nitrogen-Doped Carbon Nanodots for Non-Invasive Photoacoustic Imaging and Photothermal Therapy.

Multifunctional nanoparticles have been widely investigated for biomedical applications, such as imaging, therapy, and drug delivery. Especially, photoactive nanoparticles have received great attention as theranostic agents because of their heat-generating abilities after exposure to laser irradiation. However, photostability and safety issues have been the technical hurdles for further clinical applications. Here, we designed nitrogen (N)-doped carbon nanodots (N-CNDs) that have strong absorption in the near-infrared region, high photostability, and excellent biodegradability. Optimized N-CNDs can be utilized not only as a new photoacoustic (PA) imaging agent but also as a superior photothermal therapy (PTT) agent in vivo because of their strong optical absorption at a specific wavelength. We used N-CNDs to perform in vivo/ex vivo noninvasive PA imaging of sentinel lymph nodes via local delivery and performed PTT for cancer ablation therapy. Finally, biodegradation and renal clearance were confirmed by performing whole-body PA monitoring and a degradation test.

Objective-free optical-resolution photoacoustic microscopy

Abstract. Optical-resolution photoacoustic microscopy (OR-PAM) becomes a premier microscopic imaging tool in biomedicine because it provides agent-free optical absorption information in tissues. By tightly focusing light to a spot, a significantly improved lateral resolution can be achieved in OR-PAM. The focal spot size is typically determined by the numerical aperture of the used objective lens. Here, we demonstrate objective-free OR-PAM using a fiber optic Bessel beam generator. In this approach, no objective lens is required and, beneficially, the complexities of conventional OR-PAM systems can be greatly relieved. We have obtained photoacoustic images of a carbon fiber with a diameter of ∼6u2009u2009μm, whose lateral resolution was measured to be better than 6 to 7 μm.

In Vivo Near Infrared Virtual Intraoperative Surgical Photoacoustic Optical Coherence Tomography.

Since its first implementation in otolaryngological surgery nearly a century ago, the surgical microscope has improved the accuracy and the safety of microsurgeries. However, the microscope shows only a magnified surface view of the surgical region. To overcome this limitation, either optical coherence tomography (OCT) or photoacoustic microscopy (PAM) has been independently combined with conventional surgical microscope. Herein, we present a near-infrared virtual intraoperative photoacoustic optical coherence tomography (NIR-VISPAOCT) system that combines both PAM and OCT with a conventional surgical microscope. Using optical scattering and absorption, the NIR-VISPAOCT system simultaneously provides surgeons with real-time comprehensive biological information such as tumor margins, tissue structure, and a magnified view of the region of interest. Moreover, by utilizing a miniaturized beam projector, it can back-project 2D cross-sectional PAM and OCT images onto the microscopic view plane. In this way, both microscopic and cross-sectional PAM and OCT images are concurrently displayed on the ocular lens of the microscope. To verify the usability of the NIR-VISPAOCT system, we demonstrate simulated surgeries, including in vivo image-guided melanoma resection surgery and in vivo needle injection of carbon particles into a mouse thigh. The proposed NIR-VISPAOCT system has potential applications in neurosurgery, ophthalmological surgery, and other microsurgeries.

Pulse Analyzing System Using Optical Coherence Tomography for Oriental Medical Application

In oriental medicine, the pulse wave of a radial artery is a critical diagnosis factor. An oriental doctor puts a finger on the radial artery to sense the pulse wave of a radial artery. The pulse wave plays an important role because its shape, pressure, and duration determine the pathological status of a patient. Chongumaekbeop, which is a traditional technique for measuring the pulse by using a finger, is sometimes believed to be not reproducible due to the subjective judgment of the measurement location and pulse signal, so we performed a clinical experiment with a developed diagnosis equipment to produce quantitative and reproducible results. In this study, we measured the pulse wave of the radial artery and quantified the speed, intensity, and power of the pulse wave using optical coherence tomography (OCT). We confirmed the applicability of the developed system through an analysis of the pulse wave. We used two OCT systems whose measurement parameters are different because of the measurement limitation and analysis of vector components of pulse movement. We gathered 25 volunteers, compared and analyzed the experiment results with four oriental medicine doctors diagnosis. The results showed an agreement of 88% in pulse speed, 64% in pulse intensity, and 72% in pulse power when comparing traditional measurements with the system using OCT. We confirmed the dynamical motion detection through the two-dimensional image to ensure the reproducibility of the developed system. Thus, if the OCT system is applied to pulse measurement systems in oriental medicine, it may partially substitute for traditional measurement methods.