The International Photoacoustic Standardisation Consortium (IPASC) emerged from SPIE 2018, established to drive consensus on photoacoustic system testing. As photoacoustic imaging (PAI) matures from research laboratories into clinical trials, it is essential to establish best-practice guidelines for photoacoustic image acquisition, analysis and reporting, and a standardised approach for technical system validation. The primary goal of the IPASC is to create widely accepted phantoms for testing preclinical and clinical PAI systems. To achieve this, the IPASC has formed five working groups (WGs). The first and second WGs have defined optical and acoustic properties, suitable materials, and configurations of photoacoustic image quality phantoms. These phantoms consist of a bulk material embedded with targets to enable quantitative assessment of image quality characteristics including resolution and sensitivity across depth. The third WG has recorded details such as illumination and detection configurations of PAI instruments available within the consortium, leading to proposals for system-specific phantom geometries. This PAI system inventory was also used by WG4 in identifying approaches to data collection and sharing. Finally, WG5 investigated means for phantom fabrication, material characterisation and PAI of phantoms. Following a pilot multi-centre phantom imaging study within the consortium, the IPASC settled on an internationally agreed set of standardised recommendations and imaging procedures. This leads to advances in: (1) quantitative comparison of PAI data acquired with different data acquisition and analysis methods; (2) provision of a publicly available reference data set for testing new algorithms; and (3) technical validation of new and existing PAI devices across multiple centres.
The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system.
This study compares fluorescence and photoacoustic (PA) imaging of ex vivo tumors and organs from tumor-bearing mice injected intravenously with ultrasmall (<3 nm) tiopronin-capped Au nanoparticles and compares the data with inductively coupled plasma mass spectrometry (ICP-MS). Good agreement is seen in particle distributions and concentrations at the organ level. The spatial resolution from the imaging techniques allows for localization of the particles within organ structures. Although the particles do not have a plasmon peak, their absorbance in the near-infrared (NIR) is sufficient for PA excitation. PA imaging shows an increase of signal as particle concentrations increase, with changes in spectrum if particles aggregate. Fluorescence imaging using the particles’ native NIR emission shows agreement in general intensity in each organ, though quenching of emission can be seen at very high concentrations. Both of these imaging techniques are noninvasive and labor-saving alternatives to organ digestion and ICP-MS and may provide insight into cellular distribution of particles. The simple construct avoids the use of toxic semiconductor materials or dyes, relying upon the gold itself for both the fluorescence and PA signal. This provides a useful alternative to more complex approaches to multimodal imaging and one that is readily translatable to the clinic.
KEYWORDS: Transducers, Signal detection, Photoacoustic imaging, Kidney, Ultrasonography, Visualization, Blood vessels, Signal to noise ratio, Photoacoustic microscopy, In vivo imaging
Photoacoustic microscopy with linear array transducers enables fast two-dimensional, cross-sectional photoacoustic imaging. Unfortunately, most ultrasound transducers are only sensitive to a very narrow angular acceptance range and preferentially detect signals along the main axis of the transducer. This often limits photoacoustic microscopy from detecting blood vessels which can extend in any direction. Rotational compounded photoacoustic imaging is introduced to overcome the angular-dependency of detecting acoustic signals with linear array transducers. An integrate system is designed to control the image acquisition using a linear array transducer, a motorized rotational stage, and a motorized lateral stage. Images acquired at multiple angular positions are combined to form a rotational compounded image. We found that the signal-to-noise ratio improved, while the sidelobe and reverberation artifacts were substantially reduced. Furthermore, the rotational compounded images of excised kidneys and hindlimb tumors of mice showed more structural information compared with any single image collected.
The use of near-infrared wavelengths for photoacoustic (PA) imaging takes advantage of the relatively low
inherent absorption of tissues and has encouraged the development of agents which show high contrast in
this range. Here, we describe the modification of a commercially available PA imaging system (Vevo
LAZR, VisualSonics, Toronto) to take advantage of the 532nm and 1064nm wavelengths inherent in the
generation of the currently tuneable range of 680 to 970nm and in the use of these two wavelengths to
assess contrast agents.
The photoacoustic imaging system generated light from a Nd/YAG laser modified to extract the 532 and
1064nm wavelengths in addition to its OPO-derived tuneable range (680 - 970 nm) and deliver this light
through a fiber integrated into a linear array transducer (LZ400, VisualSonics).
Gold nanorods (UT Austin), carbon nanotubes (Stanford U), DyLight 550 (Thermo Fisher) and blood were
imaged in a phantom (PE20 tubing) and in a hindlimb subcutaneous tumor in vivo to determine their
photoacoustic signal intensity at all wavelengths.
In the phantom and in vivo, all agents caused an enhancement of the photoacoustic signal at their respective
peak absorbance wavelengths. These results show that the 532nm and 1064nm wavelengths could prove
useful in biomedical imaging due to the contrast agents customized for them. The 1064nm wavelength in
particular has the advantage of having very low generation of endogenous signal in vivo, making agents
tuned to this wavelength ideal for targeted contrast imaging.
Photoacoustic (PA) Imaging can estimate the spatial distribution of oxygen saturation (sO2) and total hemoglobin
concentration (HbT) in blood, and be co-registered with B-Mode ultrasound images of the surrounding anatomy. This
study will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound
(μUS) system that is capable of creating such images. The system will then be validated in vivo against a complementary
technique for measuring partial pressure of oxygen in blood (pO2). The pO2 estimates are converted to sO2 values based
on a standard dissociation curve found in the literature. Finally, the system will be used for assessing oxygenation in a
murine model of ischemia, both during injury and recovery.
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