Optical Light Sources and Wavelengths within the Visible and Near-Infrared Range Using Photoacoustic Effects for Biomedical Applications.

The photoacoustic (PA) effect occurs when sound waves are generated by light according to the thermodynamic and optical properties of the materials; they are absorption spectroscopic techniques that can be applied to characterize materials that absorb pulse or continuous wave (CW)-modulated electromagnetic radiation. In addition, the wavelengths and properties of the incident light significantly impact the signal-to-ratio and contrast with photoacoustic signals. In this paper, we reviewed how absorption spectroscopic research results have been used in applying actual photoacoustic effects, focusing on light sources of each wavelength. In addition, the characteristics and compositions of the light sources used for the applications were investigated and organized based on the absorption spectrum of the target materials. Therefore, we expect that this study will help researchers (who desire to study photoacoustic effects) to more efficiently approach the appropriate conditions or environments for selecting the target materials and light sources.

Ultrasound-Responsive Nanocarriers for Breast Cancer Chemotherapy.

Breast cancer is the most common type of cancer and it is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite chemotherapy's ample use, it has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target. In this paper, we review recent developments in ultrasound-guided nanocarriers for breast cancer chemotherapy, discuss the relevant challenges, and provide insights into future directions.

Fully Customized Photoacoustic System Using Doubly Q-Switched Nd:YAG Laser and Multiple Axes Stages for Laboratory Applications.

We developed a customized doubly Q-switched laser that can control the pulse width to easily find weak acoustic signals for photoacoustic (PA) systems. As the laser was constructed using an acousto-optic Q-switcher, in contrast to the existing commercial laser system, it is easier to control the pulse repetition rate and pulse width. The laser has the following control ranges: 10 Hz-10 kHz for the pulse repetition rate, 40-150 ns for the pulse width, and 50-500 µJ for the pulse energy. Additionally, a custom-made modularized sample stage was used to develop a fully customized PA system. The modularized sample stage has a nine-axis control unit design for the PA system, allowing the sample target and transducer to be freely adjusted. This makes the system suitable for capturing weak PA signals. Images were acquired and processed for widely used sample targets (hair and insulating tape) with the developed fully customized PA system. The customized doubly Q-switched laser-based PA imaging system presented in this paper can be modified for diverse conditions, including the wavelength, frequency, pulse width, and sample target; therefore, we expect that the proposed technique will be helpful in conducting fundamental and applied research for PA imaging system applications.

Fisheye lens design for solar-powered mobile ultrasound devices.

BACKGROUND: Compared to benchtop ultrasound machines, mobile ultrasound machines require portable batteries when acquiring information regarding human tissues during outdoor activities. OBJECTIVE: A novel fisheye lens type was designed to address the charging issue where it is difficult to constantly track the sun. This method does not require the use of a mechanical motor that constantly tracks the sun to charge the portable batteries. METHODS: To obtain an optical solar power system, the numerical aperture (NA) and field angle must be increased. Therefore, we use the fisheye lens with the largest field angle. RESULTS: The NA of the designed fisheye lens system reaches 0.75, allowing light collection of approximately ± 48∘. Additionally, the efficiency ratio of the central and surrounding areas also satisfies more than 80% at a field angle of 85∘ and more than 70% at field angles of 85∘ to 90∘, respectively. CONCLUSIONS: We designed a novel fisheye lens for solar-powered mobile ultrasound machines used outdoors.

A Macro Lens-Based Optical System Design for Phototherapeutic Instrumentation.

Light emitting diode (LED) and ultrasound have been powerful treatment stimuli for tumor cell growth due to non-radiation effects. This research is the first preliminary study of tumor cell suppression using a macro-lens-supported 460-nm LED combined with high-frequency ultrasound. The cell density, when exposed to the LED combined with ultrasound, was gradually reduced after 30 min of induction for up to three consecutive days when 48-W DC, 20-cycle, and 50 Vp-p sinusoidal pulses were applied to the LEDs through a designed macro lens and to the ultrasound transducer, respectively. Using a developed macro lens, the non-directional light beam emitted from the LED could be localized to a certain spot, likewise with ultrasound, to avoid additional undesirable thermal effects on the small sized tumor cells. In the experimental results, compared to LED-only induction (14.49 ± 2.73%) and ultrasound-only induction (13.27 ± 2.33%), LED combined with ultrasound induction exhibited the lowest cell density (6.25 ± 1.25%). Therefore, our measurement data demonstrated that a macro-lens-supported 460-nm LED combined with an ultrasound transducer could possibly suppress early stage tumor cells effectively.

Ultrawide-angle optical system design for light-emitting diode-based ophthalmology and dermatology applications.

BACKGROUND: Compared to laser, light-emitting diodes - non-coherent and divergent light sources requires that the developed optical system support steering and focusing of light on the desired target when acquiring information regarding human tissues. OBJECTIVE: A new optical system with an ultrawide angle was designed to cover large areas of the eye, including facial areas near the eye, in order to overcome the limited field of view of optical systems used for ophthalmology and dermatology applications. METHODS: To achieve a compact and handheld optical system for ophthalmology and dermatology applications, a contrast auto-focus (AF) method must be used, and the weight reduction of the AF group is considered during the design process to satisfy the effective focal length (EFL), back focal length (BFL), and front focal length (FFL) in the proposed optical system using Gaussian-bracket method. RESULTS: The designed optical system can focus from infinity to a magnification of -0.19 times, representing a distance of 114.359 mm from the first surface of the optical system to the object. The AF lens moving distance from infinity to the minimum distance is approximately 4.984 mm. The full width at half maximum (FWHM) values of the red, green, and blue light-emitting diodes were 16 mm, 35 mm, and 22 mm, respectively. CONCLUSIONS: We have designed an ultrawide-angle optical system for compact optical systems that are suitable for high-performance ophthalmology and dermatology applications.

Chromatic aberration free reflective mirror-based optical system design for multispectral photoacoustic instruments.

BACKGROUND: Current multispectral photoacoustic instruments must use large and separate combinational structures to obtain various biological tissue information for multispectral ranges. OBJECTIVE: The optical aberration generated from the multispectral photoacoustic systems may reduce the image quality of biological tissue because the improper structures for combining light of different wavelength cannot produce good optical ray convergence points. To prevent this, complex combined structures need to be considered at the design level for multispectral photoacoustic systems. METHODS: In place of an optical refracted lens system, reflective mirrors could be designed for optical systems. To verify our proposed idea, we assessed optical distortion performance using red, green, and blue light, and combined optical light sources to compare their chromatic aberration characteristics. RESULTS: The high optical performance is realized regardless of the wavelength for a light source combined with multiple wavelengths, because our optical system was designed with only a reflective surface. CONCLUSIONS: The designed optical system using a reflective mirror can provide multispectral optical sources (such as infrared, visible, and ultraviolet optical lights) with only one light ray path, without any chromatic aberrations.

Development of a Multiwavelength Visible-Range-Supported Opto⁻Ultrasound Instrument Using a Light-Emitting Diode and Ultrasound Transducer.

A new multiwavelength visible-range-supported opto⁻ultrasound instrument using a light-emitting diode and ultrasound transducer was developed in order to produce multiwavelength visible light with minimized color aberration errors, and detect ultrasound signals emitted from the target. In the instrument, the developed optical systems can provide multiwavelength optical transmission with low optical aberration within 10-cm ranges that are reasonably flat in the modulation transfer function at spatial frequencies of 20 and 40 lp/mm, except at the end of the diagonal edge of the samples. To assess the instrument capability, we performed pulse⁻echo responses with Thunnus obesus eye samples. Focused red, green, blue and white light rays from an integrated red, green and blue LED source were produced, and echo signal amplitudes of 33.53, 34.92, 38.74 and 82.54 mV, respectively, were detected from the Thunnus obesus eye samples by a 10-MHz focused ultrasound transducer. The center frequencies of the echo signal when producing red, green, blue and white LED light in the instrument were 9.02, 9.05, 9.21 and 8.81 MHz, respectively. From these tests, we verify that this instrument can combine red, green and blue LED light to cover different wavelengths in the visible-light range and detect reasonable echo amplitudes from the samples.

Development of novel adjustable focus head mount display for concurrent image-guided treatment applications.

PURPOSE: A conventional see-through head mount display contains many optical lenses, which can be problematic in image-guided treatment applications due to its size, weight, structure, and focus limitation. Therefore, we have designed a new type of see-through head mount display with a reduced number of optical lenses and an adequate optical resolution that can be utilized for image-guided treatment applications. MATERIALS AND METHODS: A new type of adjustable focus head mount display with expanded virtual images and an external treatment space that can be provided to the eyes of a user by enlarging the images of a small display is designed and investigated in this study. This type of head mount display can be used in image-guided treatment applications because of the dual paths of imaging and treatment from the optical systems. Therefore, this system with an adjustable focus function can aid doctors in obtaining images for the treatment of the eyes of patients because every patient has a unique pupil size. RESULTS: The results of the adjustable focus see-through head mount display showed distortion values of +0.36% in the +1 diopter location and -0.55% in the -4 diopter location, and there are less significant modulation transfer function differences within the ±5 diopter locations. CONCLUSIONS: Low optical distortions within ±0.5 diopters can help doctors image the eye conditions of patients through fewer image processing techniques. Therefore, the designed adjustable focus head mount display can provide low optical aberrations and high optical modulation transfer function resolutions for image-guided treatment applications.

Combinational light emitting diode-high frequency focused ultrasound treatment for HeLa cell.

PURPOSE: Light sources such as laser and light emitting diode or ultrasound devices have been widely used for cancer therapy and regenerative medicines, since they are more cost-effective and less harmful than radiation therapy, chemotherapy or magnetic treatment. Compared to laser and low intensity ultrasound techniques, light emitting diode and high frequency focused ultrasound shows enhanced therapeutic effects, especially for small tumors. MATERIALS AND METHODS: We propose combinational light emitting diode-high frequency focused ultrasound treatment for human cervical cancer HeLa cells. Individual red, green, and blue light emitting diode light only, high frequency focused ultrasound only, or light emitting diode light combined with high frequency focused ultrasound treatments were applied in order to characterize the responses of HeLa cells. RESULTS: Cell density exposed by blue light emitting diode light combined with high frequency focused ultrasound (2.19 ± 0.58%) was much lower than that of cells exposed by red and green light emitting diode lights (81.71 ± 9.92% and 61.81 ± 4.09%), blue light emitting diode light (11.19 ± 2.51%) or high frequency focused ultrasound only (9.72 ± 1.04%). CONCLUSIONS: We believe that the proposed combinational blue light emitting diode-high frequency focused ultrasound treatment could have therapeutic benefits to alleviate cancer cell proliferation.

Development of a Double-Gauss Lens Based Setup for Optoacoustic Applications.

In optoacoustic (photoacoustic) systems, different echo signal intensities such as amplitudes, center frequencies, and bandwidths need to be compensated by utilizing variable gain or time-gain compensation amplifiers. However, such electronic components can increase system complexities and signal noise levels. In this paper, we introduce a double-Gauss lens to generate a large field of view with uniform light intensity due to the low chromatic aberrations of the lens, thus obtaining uniform echo signal intensities across the field of view of the optoacoustic system. In order to validate the uniformity of the echo signal intensities in the system, an in-house transducer was placed at various positions above a tissue sample and echo signals were measured and compared with each other. The custom designed double-Gauss lens demonstrated negligible light intensity variation (±1.5%) across the illumination field of view (~2 cm diameter). When the transducer was used to measure echo signal from an eye of a bigeye tuna within a range of ±1 cm, the peak-to-peak amplitude, center frequency, and their -6 dB bandwidth variations were less than 2 mV, 1 MHz, and 6%, respectively. The custom designed double-Gauss lens can provide uniform light beam across a wide area while generating insignificant echo signal variations, and thus can lower the burden of the receiving electronics or signal processing in the optoacoustic system.

A Novel Fisheye-Lens-Based Photoacoustic System.

This paper presents a novel fisheye-lens-based photoacoustic (PA) system. In conventional PA systems, mechanical motors are utilized to obtain the target information due to the small fields of view of such systems. The use of such motors introduces mechanical noise, which is difficult to remove when processing the echo signals. A fisheye lens system offering a wide field of view would effectively reduce the motor effects (i.e., the noise) and enable the system to have a wide field of view. Therefore, in this work, we propose a novel fisheye lens scheme and describe a PA system based on the developed lens scheme. In addition, to confirm the feasibility of the fisheye-lens-based PA system, we present the typical pulse-echo responses obtained using a 20 MHz single element immersion transducer and the echo signals measured from bull's eye tissue samples separated by approximately 4, 6, 8, and 10 cm diagonally and 2 cm vertically from the fisheye lens. The experimental results demonstrate that the echo signal amplitudes, their center frequencies, and the -6 dB bandwidths obtained using red, green, and blue lights and a fisheye lens are acceptable when the fisheye lens is separated from a sample both diagonally and vertically. Therefore, fisheye-lens-based PA systems could be a potential method of achieving wide fields of view while reducing the mechanical motor effects.