Research

What is Photoacoustic/Optoacoustic imaging:

Photoacoustic imaging/Optoacoustic imaging (PAI/OAI) is an emerging hybrid biomedical imaging technique, capitalizing on light and sound that renders optical absorption contrast images at high ultrasonic spatial resolution. OAI finds diverse clinical applications encompassing molecular imaging, breast cancer detection, brain imaging, sentinel lymph node mapping, vasculature visualization, temperature monitoring, tissue engineering, cancer screening, and tumor angiogenesis imaging, among others. In OAI, pulsed laser light illuminates the target object, such as biological tissue. Absorption of light energy by tissue chromophores like red blood cells, melanin, and water induces a local temperature increase, resulting in tissue thermal expansion and the emission of pressure waves known as optoacoustic (OA) waves. These OA waves are then captured by a single-element ultrasound transducer or an array of ultrasound transducers. More basics in M. Xu et al., Rev. Sci. Instrum. 77 (2006), L.V.Wang et. al., IEEE JSTQE 14 (2008), L.V.Wang et al., Science 335 (2012) etc.

Spiral volumetric optoacoustic tomography (SVOT):

The rapid monitoring of biological dynamics across various murine organs using existing commercially available whole-body preclinical imaging systems is impeded by their restricted contrast, sensitivity, and spatial or temporal resolution.  We developed spiral volumetric optoacoustic tomography (SVOT) that offers optical contrast with an unparalleled degree of spatial and temporal resolution by swiftly scanning a mouse with spherical arrays, thereby addressing the existing limitations in whole-body imaging. This technique allows for the visualization of deep-seated structures within living mammalian tissues in the near-infrared spectral window, while also delivering unmatched image quality and abundant spectroscopic optical contrast. More details in Kalva et al., Photonics Research 9 (6), (2021), Kalva et al., Photoacoustics 30 (2023), Kalva et al., Nature Protocols 18 (2023).

Rapid volumetric tracking of nanoagent kinetics in mice at sub-organ level:

Large-scale visualization of nanoparticle kinetics is crucial for optimizing drug delivery and assessing in vivo toxicity of engineered nanomaterials. However, real-time tracking of nanoparticulate agents across multiple murine organs faces challenges with current whole-body preclinical imaging systems due to limitations in contrast, sensitivity, and spatial or temporal resolution. In this work, by employing single-sweep volumetric optoacoustic tomography (sSVOT) we demonstrated rapid volumetric tracking of gold nanoagent kinetics and biodistribution in mice at a suborgan level at a spatial resolution of 130 μm and sub-picomolar sensitivity. We observed clearance dynamics of purposely synthesized gold nanorods and nanorod clusters with varying sizes and surface chemistries, along with their accumulation in the liver and spleen. The ability to image rapid whole-body kinetics at suborgan scales opens new possibilities for developing and characterizing diagnostic and therapeutic nanoagents. More details in Kalva et al., ACS Applied Materials & Interfaces 14 (1), (2022).

Full-view LED-based optoacoustic tomography (FLOAT) system:

Optoacoustic tomography is traditionally conducted using bulky and costly short-pulsed solid-state lasers, delivering high per-pulse energies in the millijoule range. However, light-emitting diodes (LEDs) offer a more economical and portable solution, ensuring excellent pulse-to-pulse stability. In this work, we developed the Full-view LED-based Optoacoustic Tomography (FLOAT) system for deep tissue in vivo imaging. FLOAT utilizes a custom-made electronic unit to drive a stacked array of LEDs, achieving a pulse width of 100 ns and highly stable total per-pulse energy of 0.48 mJ with a standard deviation of 0.62%. By integrating the illumination source into a circular array of cylindrically-focused ultrasound detection elements, FLOAT overcomes limited-view effects, improving the effective field-of-view and image quality for cross-sectional (2D) imaging. More details in X. Liu, S. K. Kalva et al., Photoacoustics 31, (2023).

Second generation desktop PLD-PAT system:

By using multiple acoustic reflector based single-element ultrasound transducers (SUTR/USTR) and integrating low-cost pulsed laser diode (PLD) into the circular PAT scanner, we developed a second generation low-cost, compact, and high-speed desktop PLD-PAT-G2 imaging system. We achieved fastest cross-sectional imaging speed of 0.5 sec (2Hz frame rate) without using any expensive ultrasound array transducer. In spite of low pulse energy we obtained high quality PAT cross-sectional imaging with 0.5 sec imaging speed and up to 3 cm imaging depth in biological tissue. Fast uptake and clearance of dye can be monitored with such system. More details in Kalva et al., Optics Letters 44 (2019), Kalva et al., Journal of Visualized Experiments 147 (2019).

Compact PAT system using acoustic reflector:

A typical photoacoustic tomography (PAT) system uses a Q-switched Nd:YAG laser for irradiating the sample and a single-element ultrasound transducer (UST) for acquiring the photoacoustic data. Conventionally, in PAT systems, the UST is held in a horizontal position and moved in a circular motion around the sample in full 2π radians. Horizontal positioning of the UST requires a large water tank to house, and load on the motor is also high. To overcome this limitation, we used the UST in the vertical plane instead of the horizontal plane. The photoacoustic (PA) waves generated from the sample are directed to the detector surface using an acoustic reflector (made of stainless steel) placed at 45 deg to the transducer body. Hence, we can reduce the scanning radius, which in turn will reduce the size of the water tank and load on the motor, and the overall conventional PAT system size can be minimized. Use of acoustic reflector doesn't effect spatial resolution of the PAT system, or the bandwidth of ultrasound transducer and renders similar quality images as that of conventional UST. More details in Kalva et al., Journal of Biomedical Optics 22 (2017). 

Image reconstruction:

Improvement of tangential resolution in PAT:

In a circular scanning geometry based PAT systems, the spatial resolution along radial direction (axial resolution) is spatially invariant, and is dependent on ultrasound transducer (detector) bandwidth and not affected by the detector aperture size. Whereas spatial resolution perpendicular to axial direction (tangetial/lateral resolution) is spatially variant (depending on the location from the scanning center) and is dependent on detector bandwidth and the aperture (size) of the detector as well. Several approaches have been proposed such as using negative acoustic lens infront of the unfocused (flat) transducer, or by using virtual point detectors. Here, we have used modified delay-and-sum reconstruction technique that provided three-fold improvement in tangential resolution using flat (unfocused) and cylindrical (focused) ultrasound detectors in PAT. We have also shown that this technique can preserve the shape and size of the sample tragets. More details in Kalva et al., Journal of Biomedical Optics 21 (2016).  

Research Highlights:

March 2021: Our work on flash scanning volumetric optoacoustic tomography (fSVOT) system was published as cover page in Laser & Photonics Reviews. [Link]

February 2019: Our work on Pulsed laser diode based desktop photoacoustic tomography system for high-speed imaging was featured as highlights in Biophotonics World. [Link]