Photoacoustic imaging (PAI) has traditionally relied on slow, fragile and expensive lasers as excitation sources. Advances in solid-state device technology have recently resulted in the development of a new class of high power light emitting diodes (LEDs) that can be used as fast, robust and cheap excitation sources for PAI.
Here, we report the characterization and technical validation of a dual-mode multi-wavelength LED-based PAI/ultrasound imaging system (AcousticX) that has the potential to perform real-time in vivo imaging. LEDs operating with a pulse length of 70 ns and a repetition rate of up to 4 KHz at wavelengths of 690, 750, 810, 850 and 980 nm were tested. Ultrasound detection was made using a linear-array transducer with a center frequency of 10.05 MHz and a fractional bandwidth of 77%. We performed several systematic studies to evaluate the precision, penetration depth, spatial resolution, and sensitivity of the system. Measurements were made in tissue-mimicking phantoms to independently assess the impact of system variables on precision, including sample positioning and frame averaging. Temporal variation was assessed by repeated measurements over minutes, hours and days in the phantoms. Sensitivity to spectral differences was established by imaging the phantoms using all available multi-wavelength LEDs. The LED-based PAI system was able to detect small molecule dyes at 500 nM concentration at depth and to differentiate oxy- and deoxy-hemoglobin in mouse blood. Our studies indicate that LED-based PAI would be capable of providing real-time structural, functional and molecular imaging information up to depths of 2.5 cm in tissue.
Minimally invasive fetal interventions, such as those used for therapy of twin-to-twin transfusion syndrome (TTTS), require accurate image guidance to optimise patient outcomes. Currently, TTTS can be treated fetoscopically by identifying anastomosing vessels on the chorionic (fetal) placental surface, and then performing photocoagulation. Incomplete photocoagulation increases the risk of procedure failure. Photoacoustic imaging can provide contrast for both haemoglobin concentration and oxygenation, and in this study, it was hypothesised that it can resolve chorionic placental vessels. We imaged a term human placenta that was collected after caesarean section delivery using a photoacoustic/ultrasound system (AcousticX) that included light emitting diode (LED) arrays for excitation light and a linear-array ultrasound imaging probe. Two-dimensional (2D) co-registered photoacoustic and B-mode pulse-echo ultrasound images were acquired and displayed in real-time. Translation of the imaging probe enabled 3D imaging. This feasibility study demonstrated that photoacoustic imaging can be used to visualise chorionic placental vasculature, and that it has strong potential to guide minimally invasive fetal interventions.
KEYWORDS: Lymphatic system, Veins, Imaging systems, Light emitting diodes, Visualization, Blood, In vivo imaging, Real time imaging, Absorption, Blood vessels, Photoacoustic imaging, Ultrasound real time imaging
Non-invasive in vivo imaging of lymphatic system is of paramount importance for analyzing the functions of lymphatic vessels, and for investigating their contribution to metastasis. Recently, we introduced a multi-wavelength real-time LED-based photoacoustic/ultrasound system (AcousticX). In this work, for the first time, we demonstrate that AcousticX is capable of real-time imaging of human lymphatic system. Results demonstrate the capability of this system to image vascular and lymphatic vessels simultaneously. This could potentially provide detailed information regarding the interconnected roles of lymphatic and vascular systems in various diseases, therefore fostering the growth of therapeutic interventions.
Photoacoustic imaging is a hybrid biomedical imaging modality that has emerged over the last decade. In photoacoustic imaging, pulsed-light absorbed by the target emits ultrasound that can be detected using a conventional ultrasound array. This ultrasound data can be used to reconstruct the location and spatial details of the intrinsic/extrinsic light absorbers in the tissue. Recently we reported on the development of a multi-wavelength high frame-rate LED-based photoacoustic/ultrasound imaging system (AcousticX). In this work, we photoacoustically characterize the absorption spectrum of ICG and porcine blood using LED arrays with multiple wavelengths (405, 420, 470, 520, 620, 660, 690, 750, 810, 850, 925, 980 nm). Measurements were performed in a simple reflection mode configuration in which LED arrays where fixed on both sides of the linear array ultrasound probe. Phantom used consisted of micro-test tubes filled with ICG and porcine blood, which were placed in a tank filled with water. The photoacoustic spectrum obtained from our measurements matches well with the reference absorption spectrum. These results demonstrate the potential capability of our system in performing clinical/pre-clinical multispectral photoacoustic imaging.
Recently we developed a multispectral LED-based photoacoustic/ultrasound imaging system (AcousticX) and have been continuously working on its technical/functional improvements. AcousticX is a linear array ultrasound transducer (128 elements, 10 MHz)-based system in which LED arrays (selectable wavelengths, pulse repetition frequency: 4 kHz, pulse width: tunable from 40 – 100 ns) are fixed on both sides of the transducer to illuminate the tissue for photoacoustic imaging. The ultrasound/photoacoustic data from all 128 elements can be simultaneously acquired, processed and displayed. We already demonstrated our system’s capability to perform photoacoustic/ultrasound imaging for dynamic imaging of the tissue at a frame rate of 10 Hz (for example to visualize the pulsation of arteries in vivo in human subjects). In this work, we present the development of a new high-speed imaging mode in AcousticX. In this mode, instead of toggling between ultrasound and photoacoustic measurements, it is possible to continuously acquire only photoacoustic data for 1.5 seconds with a time interval of 1 ms. With this improvement, we can record photoacoustic signals from the whole aperture (38 mm) at fast rate and can be reviewed later at different speeds for analyzing dynamic changes in the photoacoustic signals. We believe that AcousticX with this new high-speed mode opens up a feasible technical path for multiple dynamic studies, for example one which focus on imaging the response of voltage sensitive dyes. We envisage to improve the acquisition speed further in future for exploring ultra-high-speed applications.
Recently, various type of photoacoustic imaging (PAI) that can visualize properties and distribution of light absorber have been researched. We developed PAI system using LED light source and evaluated characteristics of photoacoustic signal intensity versus Indocyanine Green (ICG) concentration. In this experiment, a linear type PZT array transducer (128-elements, 10.0MHz center frequency) was used to be able to transmit and receive ultrasound and also detect photoacoustic signal from the target object. The transducer was connected to the PAI system, and two sets of LED light source that had 850nm wavelength chip array were set to the both side of the transducer. The transducer head was placed at a distance of 20 mm from the target in the water bath. The target object was a tube filled with ICG in it. The tubes containing ICG at concentrations from 300nanomolar to 3millimolar were made by diluting original ICG solution. We measured the photoacoustic signal strength from RF signal generated from the ICG in the tube, and the results showed that the intensity of the signal was almost linear response to the concentration in log-log scale.
We have successfully imaged photoacoustic differences of light absorbance between two images acquired by different wave-length LED array light source. Compared to photoacoustic imaging system using conventional solid-state laser light source, LED light source can be driven at higher frequency pulses, so we were able to get the subtraction image at higher frame rate that calculated from two images which were captured at each wave-length LED light pulse timing. We developed LED array light source which is composed to have two different wave-length chips, so each wave-length light pulse can be controlled and emitted freely. Thus LED array light source can be composed as multiple selectable wavelength more than two, and a various combination of subtraction image may become available at high frame rate.
We have achieved penetration depth of 30mm by photoacoustic imaging system using LED light source integrated transducer to image a clinical metal needle inserted into a tissue mimicking phantom. We developed the transducer that integrated near-infrared LED array light source, which was connected to a photoacoustic imaging system which drove LED array light source and controlled photoacoustic data acquisition process. Conventionally solid-state laser has been used as the light source for photoacoustic imaging system. Because LED is diffused light source, laser safety glasses is not necessary, also inflexible fibers are not used to guide light close to a transducer, and we integrated LED light source inside the transducer, which became compact and practical size for conventional ultrasound equipment users. We made LED light source unit as detachable to the transducer easily, so wave-length of light can be selectable by changing the LED light source unit.
When we consider the needle visualization in the field of point of care by utilizing the photoacoustic imaging system, and using the conventional solid state laser light source, the issue arises such as device size and not a green system due to the high power consumption. Therefore, we aimed at an environmentally friendly and compact system with low power consumption by using a NIR-LED array light source. The intensity of NIR-LED light is weak, but, by averaging photoacoustic signals with multiple pulse, we have improved S/N of the photoacoustic signal. As a result, we’ve achieved penetration depth of 30mm.
We’ve successfully measured photoacoustic signal by NIR-LED array that has very small power, approx. 1/1500 of light amount compared with Nd:YAG OPO light. In order to achieve high output power, we drove NIR-LED array with unusual amount of electric current. The experiment results showed that the photoacoustic signal strength was about 1/40 of the laser, which suggests NIR-LED array has good photoacoustic reception efficiency versus the ultrasound transducer bandwidth. NIR-LED array photoacoustic system may be able to achieve high-speed imaging which cannot be obtained by the solid-state laser. NIR-LED system can be a game changer for photoacoustic imaging.
We’ve developed NIR-LED array light source module for photoacoustic imaging system, which is ultra-small and consumes extremely low power. Conventional photoacoustic imaging system uses solid state laser light source, which consumes large amount of electricity. Instead, we’ve developed high intensity NIR-LED chips on a 1cm x 6cm board, which produces approx. 1.0kW output power and obtained photoacoustic signal by driving NIR-LED light source module with about 100 ns pulse. Comparing to the laser light source, our module is much smaller than 1/15000 the volume and less than 1/1000 the power consumption approximately. We’ve achieved penetration depth of 30mm.
We propose a Sub-Pixel Scanning (SPS) method for imaging the refraction of X-rays by an object with a single exposure.
The key feature of our SPS method is that the area where the G2 grating masks the self-image of the G1 grating
cyclically changes along the several adjoining sub-pixels by means of G2 rotation with a predetermined angle to the selfimage.
Thereby, periodically intensity-modulated signal can be acquired in a single exposure. This intensity-modulated
signal nearly corresponds to that from the each phase step signal in the phase stepping method. Accordingly, a refraction
image with the pixel size corresponding to the width of a sub-pixel set can be constructed by calculating the phase shift
in each sub-pixel data set. An experimental equipment was designed and constructed using an amorphous Selenium
(a-Se) direct conversion type Flat Panel Detector (FPD), to demonstrate the feasibility of the SPS method. An image
acquired by SPS method was comparable to that of the image by phase stepping method with multiple exposure, where
the imaging conditions, i.e. total imaging exposure dose and image resolution, are the same. We expect SPS method to
contribute to the development of the practical imaging system in clinical diagnostic use.
To increase the detection performance of breast cancers in mammograms, we need to improve shape delineation of
micro calcifications and tumors. We accomplished this by developing a direct-conversion mammography system with an
optical reading method and a new dual a-Se layer detector. The system achieved both small pixel size (50 micrometer)
and a high Detective Quantum Efficiency (DQE) realized by 100 % of fill factor and noise reduction. We evaluated
image quality performance and determined the best exposure conditions.
We measured DQE and Modulation Transfer Function(MTF) according to the IEC62220-1-2. High DQE was maintained
at a low radiation dosage, indicating that the optical reading method accompanies low noises. Response of MTF was
maintained at up to the Nyquist frequency of 10 cyc/mm, which corresponds to 50 micrometer pixel size.
To determine the best exposure conditions, we measured Contrast to Noise Ratio (CNR) and visually evaluated images
of a resected breast under conditions of MoMo, MoRh, and WRh. There were occasional disagreements between the
exposure conditions for achieving the maximum CNR and those for the best image graded by the visual evaluation. This
was probably because CNR measurement does not measure effects of scattered X-ray. The images verified the
improvement in detection and delineation performance of micro calcifications and tumors.
A novel mammography detector with dual amorphous-Selenium
(α-Se) layer has been developed that employs
photoinduced discharge in its readout procedure. The detector consists of a bias electrode, a thick α-Se layer for
x-ray-to-electron
conversion, an electron-trapping layer (ETL), a thin α-Se layer for the photoinduced discharge, alternately arranged
transparent and opaque stripe electrodes, and a linear optical source for readout. The detector directly converts
x-rays into electrons to accumulate the electrons in ETL. When photoinduced discharge arises on the transparent
electrodes through readout light irradiation, an accumulated electron image is transferred to the transparent electrodes
and detected as signals at charge amplifiers, which we call 'Photoconductive Switching' readout. Readout efficiency and
image readout speed have been improved enough to be used as a practical level by the adoption of the alternatelyarranged
stripe electrodes. Furthermore, such a simple stripe-electrode structure accomplishes low electrical-noise
readout and easy fabrication of fine-pitch pixels. A prototype 50 ìm pixel-pitch detector with the 18×24 cm imaging area
has been prepared, which shows high DQE performances more than 64, 48, and 28% at 1, 4, and 7 lp/mm, respectively,
not only in the usual dose range of around 100 μGy but at the low dose of 32 μGy. The 'Photoconductive Switching'
readout mechanism makes it possible to realize the high DQE and the finest resolution of 50 μm in the direct-conversion
detectors for full-field digital mammography.
The purpose of this study is to determine the relative effect of MTF, DQE, and pixel size on the shape of
microcalcifications in mammography. Two original images were obtained by a) scanning the film that accompanies an
RMI-156 phantom at a resolution of 25μm per pixel, b) creating an image with various shapes on a computer. Simulated
images were then obtained by changing MTF, adding noise to simulate DQE effects, and changing the resolution of the
original images. These images were visually evaluated to determine the recognition of the shape. In the evaluation of
400μm microcalcifications on the RMI-156 phantom, we found that shape recognition is maintained with a pixel size of
50μm or less regardless of MTF. However, at resolutions over 50μm, recognition was insufficient even when MTF was
increased. Adding noise decreased visibility but did not affect shape recognition. The same results were obtained using
computer-created shapes. The effect of pixel size on the recognition of the shape of microcalcifications was shown to be
greater compared to MTF and DQE. It was also found that increasing MTF does not compensate for information lost
because of enlarged pixel size.
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