SignificanceTo effectively study preclinical animal models, medical imaging technology must be developed with a high enough resolution and sensitivity to perform anatomical, functional, and molecular assessments. Photoacoustic (PA) tomography provides high resolution and specificity, and fluorescence (FL) molecular tomography provides high sensitivity; the combination of these imaging modes will enable a wide range of research applications to be studied in small animals.AimWe introduce and characterize a dual-modality PA and FL imaging platform using in vivo and phantom experiments.ApproachThe imaging platform’s detection limits were characterized through phantom studies that determined the PA spatial resolution, PA sensitivity, optical spatial resolution, and FL sensitivity.ResultsThe system characterization yielded a PA spatial resolution of 173 ± 17 μm in the transverse plane and 640 ± 120 μm in the longitudinal axis, a PA sensitivity detection limit not less than that of a sample with absorption coefficient μa = 0.258 cm − 1, an optical spatial resolution of 70 μm in the vertical axis and 112 μm in the horizontal axis, and a FL sensitivity detection limit not <0.9 μM concentration of IR-800. The scanned animals displayed in three-dimensional renders showed high-resolution anatomical detail of organs.ConclusionsThe combined PA and FL imaging system has been characterized and has demonstrated its ability to image mice in vivo, proving its suitability for biomedical imaging research applications.
KEYWORDS: Spatial resolution, Imaging systems, Ultrasonography, Photoacoustic imaging, In vivo imaging, Signal detection, Video, Functional imaging, Doppler effect, Data acquisition
We present the continued development a clinical ultrasound (US) imaging device with a photoacoustic (PA) mode. The combined USPA imaging platform is designed around a compact US component capable of B-mode, M-mode, color Doppler, and pulsed wave Doppler US imaging modes with a 128 element US probe. The PA mode can support a 256 element PA probe with real-time 2D imaging up to 20 Hz. The PA signals are amplified by a 40 dB pre-amplifier while US mode signals bypass the circuit, resulting in high quality PA images. We demonstrate the USPA platform’s capabilities using tissue-mimicking phantoms.
PhotoSound Technologies specializes in the development of electronics solutions for massive parallel data acquisition applicable to the fields of photoacoustics (PA), X-ray acoustics, including 3D dosimetry, and ultrasound. PhotoSound’s Legion ADC256 R1.1, released in 2018, is a 256-channel 12-bit ADC with a sampling rate of 40 MHz. The ADC256’s average data bandwidth is limited by its USB3 PC interface, which has a data rate up to 3 Gbps per board. Multiple ADC256 boards can operate fully in parallel. On software level configurations, multiple ADC256 boards are represented as a single ADC board with increased number of channels. The incoming ultrasound (US) upgrades and modifications of ADC256 will enable combination and alternation of US and PA modes using the same probe. PhotoSound MoleculUS is a medical-grade Telemed US system combined with a PA-optimized ADC. MoleculUS utilizes clinical US probes to produce US images which can be interleaved with PA imaging by enabling optical fiber illumination. The other ADC256 modification, advanced PAUS oriented for research, will have PCIe PC interface for raw PA and US data and arbitrary software control over beamformer profiles, limited by high-voltage power only. The data in ultrasound and photoacoustics modes is user accessible in raw format and can be delivered to CUDA GPU using MATLAB parallel computing (CUDA) toolbox or other tools. Multiple PAUS boards can work in parallel in both PA and US modes.
KEYWORDS: Skin, Luminescence, Photoacoustic spectroscopy, Tissues, 3D image processing, Animal model studies, Preclinical imaging, Spatial resolution, In vivo imaging, Acquisition tracking and pointing
We report on the development of a preclinical 3D imaging platform integrating photoacoustic tomography and fluorescence (PAFT). The proposed multimodal imaging concept addresses known deficiencies in sensitivity, anatomical registration, and spatial resolution of the individual imaging modalities. Multi-view photoacoustic and optical projections of the studied animal are utilized to reconstruct large (27 cm3) volumes showing vascular network and blood-rich tissues, as well as regions with induced optical/fluorescence contrast with 3D resolution exceeding 150 μm. An additional 532-nm low-energy pulsed laser excitation is implemented as a separate imaging channel for registration over skin topography and superficial vasculature. PAFT technology enables functional and molecular volumetric imaging using wide range of fluorescent and luminescent biomarkers, nanoparticles, and other photosensitive constructs mapped with high fidelity over robust anatomical structures of the studied animal model. We demonstrated the PAFT performance using phantoms and by in vivo imaging of preclinical murine models.
KEYWORDS: Data acquisition, Clocks, Capacitance, Interfaces, Electromagnetic coupling, Amplifiers, Connectors, Field effect transistors, Signal to noise ratio, Human-machine interfaces
Large number of simultaneously acquired spatially distinct pressure signals is required to improve quality of real-time photoacoustic and x-ray acoustic biomedical images [1]. In the past this approach was limited by availability of commercial multi-channel analog-to-digital converter (ADC) systems and ability to operate multiple ADC boards with synchronized clock and trigger source. The new Legion series single-board 256-channel ADC (ADC256) was designed by PhotoSound for massive parallel data acquisition utilized in photoacoustic, laser-induced ultrasound, and X-ray acoustic real-time imaging applications. ADC256 is a 12-bit ADC with a sampling rate up to 40 MHz and a USB3 computer interface. It can run at 200 Hz frame rate with 4096 points per trigger acquired by each channel. Higher trigger rates without data loss are possible with smaller number of points per trigger. ADC256 has an integrated amplifier with programmable gain up to 51 dB. Additionally, it can be equipped with a matching photoacoustic preamplifier. The system architecture is scalable to 1024 channels using four synchronized boards with a single trigger source. The clock and the trigger can be delivered from the master ADC256 board (daisy chain) or from the clock and trigger server (star topology). The data collected by each ADC board has trigger and board stamps allowing to (a) use multiple computers for data acquisition, and (b) detection of lost data events, even if the trigger rate exceeds its maximum allowed value.
We have developed a preclinical 3D imaging instrument integrating photoacoustic tomography and fluorescence (PAFT) addressing known deficiencies in sensitivity and spatial resolution of the individual imaging components. PAFT is designed for simultaneous acquisition of photoacoustic and fluorescence orthogonal projections at each rotational position of a biological object, enabling direct registration of the two imaging modalities. Orthogonal photoacoustic projections are utilized to reconstruct large (21 cm3 ) volumes showing vascularized anatomical structures and regions of induced optical contrast with spatial resolution exceeding 100 µm. The major advantage of orthogonal fluorescence projections is significant reduction of background noise associated with transmitted or backscattered photons. The fluorescence imaging component of PAFT is used to boost detection sensitivity by providing low-resolution spatial constraint for the fluorescent biomarkers. PAFT performance characteristics were assessed by imaging optical and fluorescent contrast agents in tissue mimicking phantoms and in vivo. The proposed PAFT technology will enable functional and molecular volumetric imaging using fluorescent biomarkers, nanoparticles, and other photosensitive constructs mapped with high fidelity over robust anatomical structures, such as skin, central and peripheral vasculature, and internal organs.
We introduce a preclinical imaging platform – a 3D photoacoustic/fluorescence tomography (PAFT) instrument augmented with an environmentally responsive dual-contrast biocompatible nanoprobe. The PAFT instrument was designed for simultaneous acquisition of photoacoustic and fluorescence orthogonal projections at each rotational position of a biological object, enabling direct co-registration of the two imaging modalities. The nanoprobe was based on liposomes loaded with J-aggregates of indocyanine green (PAtrace). Once PAtrace interacts with the environment, a transition from J-aggregate to monomeric ICG is induced. The subsequent recovery of monomeric ICG is characterized by dramatic changes in the optical absorption spectrum and reinstated fluorescence. In the activated state, PAtrace can be simultaneously detected by both imaging modes of the PAFT instrument using 780 nm excitation and fluorescence detection at 810 nm. The fluorescence imaging component is used to boost detection sensitivity by providing lowresolution map of activated nanoprobes, which are then more precisely mapped in 3D by the photoacoustic imaging component. Activated vs non-activated particles can be distinguished based on their different optical absorption peaks, removing the requirements for complex image registration between reference and detection scans. Preliminary phantom and in vivo animal imaging results showed successful activation and visualization of PAtrace with high sensitivity and resolution. The proposed PAFT-PAtrace imaging platform could be used in various functional and molecular imaging applications including multi-point in vivo assessment of early metastasis.
We describe the ongoing development and performance of a high-pulse-energy wavelength-cycling laser system for three-dimensional optoacoustic tomography of the breast. Joule-level energies are desired for achieving the required penetration depths while maintaining safe fluence levels. Wavelength cycling provides a pulse sequence which repeatedly alternates between two wavelengths (approximately 756 and 797 nm) that provide differential imaging. This improves co-registration of captured differential images and quantification of blood oxygen saturation. New design features have been developed for and incorporated into a clinical prototype laser system, to improve efficacy and ease of use in the clinic. We describe the benefits of these features for operation with a clinical pilot optoacoustic / ultrasound dual-modality three-dimensional imaging system.
In this work we introduce an improved prototype of three-dimensional imaging system that combines optoacoustic tomography (OAT) and laser ultrasound tomography (LUT) to obtain coregistered maps of tissue optical absorption and speed of sound (SoS). The OAT scan is performed by a 360 degree rotation of a mouse with respect to an arc-shaped array of ultrasonic transducers. A Q-switched laser system is used to establish optoacoustic illumination pattern appropriate for deep tissue imaging with a tunable (730-840 nm) output wavelengths operated at 10 Hz pulse repetition rate. A 532 nm wavelength output, being mostly absorbed within a narrow superficial layer of skin, is used to outline the visualized biological object. Broadband laser ultrasound emitters are arranged in another arc pattern and are positioned opposite and orthogonal to the array of transducers. This imaging geometry allows reconstruction of volumes that depict SoS distributions from the measured time of flight data. The reconstructed LUT images can subsequently be employed by an optoacoustic reconstruction algorithm to compensate for acoustic wavefield aberration and thereby improve accuracy of the reconstructed images of the absorbed optical energy. The coregistered OAT-LUT imaging is validated in a phantom and live mouse using a single-slice system prototype.
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