Deep tissue photoacoustic computed tomography with a fast and compact laser system

Abstract

Photoacoustic computed tomography (PACT) holds great promise for biomedical imaging, but wide-spread implementation is impeded by the bulkiness of flash-lamp-pumped laser systems, which typically weigh between 50 -200 kg, require continuous water cooling, and operate at a low repetition rate. Here, we demonstrate that compact lasers based on emerging diode technologies are well-suited for preclinical and clinical PACT. The diodepumped laser used in this study had a miniature footprint (13 × 14 × 7 cm 3 ), weighed only 1.6 kg, and outputted up to 80 mJ per pulse at 1064 nm. In vitro, the laser system readily provided over 4 cm PACT depth in chicken breast tissue. In vivo, in addition to high resolution, non-invasive brain imaging in living mice, the system can operate at 50 Hz, which enabled high-speed cross-sectional imaging of murine cardiac and respiratory function. The system also provided high quality, high-frame rate, and non-invasive three-dimensional mapping of arm, palm, and breast vasculature at multi centimeter depths in living human subjects, demonstrating the clinical viability of compact lasers for PACT.

Photoacoustic imaging in the second near-infrared window: a review

“…[146][147][148] Recently, using hemoglobin contrast, different organs (brain, heart, liver, and kidneys) of mouse were imaged using PAT at 1064 nm. 149 The imaging system used a compact high-energy 1064-nm diode-pumped Nd:YAG laser [ Fig. 5(a)] with the following specifications: 3.2 ðLÞ × 14.0 ðWÞ × 6.5 ðHÞ cm, weight ∼1.6 kg, M 2 -factor (beam quality factor) ∼3, pulse energy ∼80 mJ, and pulse repetition rate 1 to 50 Hz, from Montfort Laser GmbH, Austria.…”

“…12(a). 149 The system uses a compact 1064-nm laser (described in Sec. 4.2) and a bifurcated fiber bundle with circular input (1-cm diameter) and two line outputs (5-cm length) to deliver light to the arm/palm.…”

“…169 Although the above studies have used NIR-II agents, NIR-II window has shown its potential for PAI without an exogenous agent: in vivo small animal brain imaging and whole body of small animals using blood contrast at 1064 nm. 149,150 In vivo human imaging at 1064 nm was successfully demonstrated by imaging human palm/arm, 149 and breast 36 without a contrast agent. The cross section of the monkey brain cortex with a skull thickness of ∼2 mm was imaged at 1064 nm with energy density of 50 mJ∕cm 2 .…”

Low-cost photoacoustic imaging systems based on laser diode and light-emitting diode excitation

“…65 Currently, pulsed laser diodes are commercially available with a hundreds-watt-level power output at near-infrared (NIR) wavelengths, and continuous-wave (CW) LEDs can cover the full visible (VIS) spectrum. [66][67][68][69][70][71][72][73][74][75][76][77] They could play a broad role in super¯cial vascular PAI, especially where the laser energy requirements are relatively modest. Although the relatively weak power represents a main disadvantage for e±cient photoacoustic e®ect, there is still substantial scope to mitigate this for deeper imaging depth by time and frequency methods.…”

Nonlinear Photoacoustic Imaging by in Situ Multiphoton Upconversion and Energy Transfer

“…Both types of systems are commonly used in the PAT field. 13–14 For pulsed-PAT, we used a two-photon dye (AF-350) as the upconverting medium, because it responds to ~800 nm nanosecond to femtosecond laser pulses and possesses two-photon excited emission with high efficiency in the visible region. 15–16 For CW-PAT, we used lanthanide-doped upconverting nanoparticles (UCNPs), because their upconverting luminescence efficiencies are much higher under CW irradiation due to the long fluorescence lifetime of lanthanide ions (~ microsecond).…”