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High-spatiotemporal resolution microwave-induced thermoacoustic tomography for imaging biological dynamics in deep tissue

July 2024
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Biological systems undergo constant dynamic changes across various spatial and temporal scales. To investigate the intricate biological dynamics in living organisms, there is a strong need for high-speed and high-resolution imaging capabilities with significant imaging depth. In this work, we present high-spatiotemporal resolution microwave-induced thermoacoustic tomography (HR-MTAT) as a method for imaging biological dynamics in deep tissues. HR-MTAT utilizes nanosecond pulsed microwave excitation and ultrasound detection, with appropriate spatial configurations, to achieve high coupling of the sample to the microwaves, to produce images in soft tissue with dielectric contrast and sub-millimeter spatial resolution (230 μm), to a depth of a few centimeters. Notably, by employing a 128-channel parallel signal acquisition and digitization strategy, the field programmable gate array module manages data synthesis, and GPU-based parallel pixel reconstruction facilitates HR-MTAT to accomplish single-frame image reconstruction in an impressive 50 μs. The practical feasibility of HR-MTAT was evaluated in live mice. The results show that HR-MTAT can noninvasively image whole-body small animals (up to 60 mm in depth) with clear resolution of internal organ structures at a frame rate of 100 Hz, without the need for labeling. At this high spatiotemporal resolution, HR-MTAT can capture respiration, heartbeat, and arterial pulse propagation without motion artifacts and track bio-nanoprobes in livers and tumors. These findings demonstrate HR-MTAT's ability to perform dynamic imaging with high contrast and resolution in deep tissues.

Schematic and performance of HR-MTAT. (a) The device diagram of the HR-MTAT. (b) Schematic diagram of microwave illumination and ultrasound field focusing. (c) Correspondence between microwave impulse duration and duration of the excited TA signal. (d) HR-MTAT image of copper wire (the blue dotted line in the lower left corner indicates the position of the ultrasonic transducer, and the black dot indicates the imaging position of the copper wire). (e) The resolution of HR-MTAT. (f) Frequency analysis of TA signal in (e).

…

HR-MTAT anatomy images. (a)–(d) HR-MTAT anatomy images of the lower, middle, and upper of the mouse liver and head, respectively.

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HR-MTAT label-free dynamics analysis. (a) HR-MTAT anatomy images of the mouse chest. (b) Fourier analysis of heart wall and lung edge motion. (c) One-dimensional TA signal analysis of skin, heart wall, and lung edge motion. (d) HR-MTAT liver anatomy image. (e) Cross sections of the vessels highlighted by the arrows in (a). (f) Changes associated with arterial impulse propagation. AA: aorta abdominals.

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Bio-nanoprobe tracking by HR-MTAT. (a) and (b) Liver anatomy images corresponding to 0 and 3 h. (c) Percentage of TA signal enhancement in the region of interest. (d) The anatomy images of liver at 0, 0.5, 3, 6, and 12 h were obtained. (e) and (f) Tumor anatomy images corresponding to 0 and 3 h. (g) Percentage of TA signal enhancement in the region of interest. (h) The anatomy images of tumor at 0, 0.5, 3, 6, 12, and 48 h were obtained.

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High-spatiotemporal resolution

microwave-induced thermoacoustic tomography

for imaging biological dynamics in deep tissue

Cite as: Appl. Phys. Lett. 125, 023701 (2024); doi: 10.1063/5.0216061

Submitted: 27 April 2024 .Accepted: 9 June 2024 .

Published Online: 8 July 2024

Yu Wang,

1,2,3

Xiaoyu Tang,

1,2,3

and Huan Qin

1,2,3,a)

AFFILIATIONS

MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics,

South China Normal University, Guangzhou 510631, China

Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University,

Guangzhou 510631, China

Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University,

Guangzhou 510631, China

Author to whom correspondence should be addressed: qinghuan@scnu.edu.cn

ABSTRACT

Biological systems undergo constant dynamic changes across various spatial and temporal scales. To investigate the intricate biological

dynamics in living organisms, there is a strong need for high-speed and high-resolution imaging capabilities with significant imaging depth.

In this work, we present high-spatiotemporal resolution microwave-induced thermoacoustic tomography (HR-MTAT) as a method for imag-

ing biological dynamics in deep tissues. HR-MTAT utilizes nanosecond pulsed microwave excitation and ultrasound detection, with appro-

priate spatial configurations, to achieve high coupling of the sample to the microwaves, to produce images in soft tissue with dielectric

contrast and sub-millimeter spatial resolution (230 lm), to a depth of a few centimeters. Notably, by employing a 128-channel parallel signal

acquisition and digitization strategy, the field programmable gate array module manages data synthesis, and GPU-based parallel pixel recon-

struction facilitates HR-MTAT to accomplish single-frame image reconstruction in an impressive 50 ls. The practical feasibility of HR-

MTAT was evaluated in live mice. The results show that HR-MTAT can noninvasively image whole-body small animals (up to 60 mm in

depth) with clear resolution of internal organ structures at a frame rate of 100 Hz, without the need for labeling. At this high spatiotemporal

resolution, HR-MTAT can capture respiration, heartbeat, and arterial pulse propagation without motion artifacts and track bio-nanoprobes

in livers and tumors. These findings demonstrate HR-MTAT’s ability to perform dynamic imaging with high contrast and resolution in deep

tissues.

Published under an exclusive license by AIP Publishing. https://doi.org/10.1063/5.0216061

The essence of biokinetics is to reveal physiological activities and

interactions within an organism from the microscopic to mesoscopic

level, including microscopic processes such as bioelectrical activity and

ion channel regulation within individual cells, as well as holistic phe-

nomena such as cellular interactions and changes in the distribution of

tissue electrical conductivity. Many physiological mechanisms or dis-

eases can lead to imbalances in ion distribution or changes in local

electrical conductivity rapidly.

1,2

Detection of kinetic features at rele-

vant anatomical sites therefore provides essential physiological and

pathological information that is critical for elucidating the functional

regulation of organisms and disease progression. Recent work has

demonstrated the potential of optical methods for the sustained,

noninvasive detection of kinetic information, including ion levels, tem-

perature, blood oxygen, and conductivity.

3–6

Measurements are limited

to optical conventional depth, and attenuation in biological tissues lim-

its the use of this mechanism in deep tissues. Methods for the study of

deep tissue dynamics, such as computed tomography (CT), x-ray

imaging, or ultrasound imaging, are usually associated with a risk of

radiation exposure, invasiveness, or insufficient contrast.

7–11

In this

context, advanced noninvasive, ionizing radiation-free, high-temporal

and high-spatial resolution, and high-contrast imaging techniques for

deep tissue dynamics are of increasing interest.

Long-wavelength electromagnetic waves are highly penetrating in

biological tissues without the risk of ionizing radiation and have great

Appl. Phys. Lett. 125, 023701 (2024); doi: 10.1063/5.0216061 125, 023701-1

Published under an exclusive license by AIP Publishing

Applied Physics Letters ARTICLE pubs.aip.org/aip/apl

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High-spatiotemporal resolution microwave-induced thermoacoustic tomography for imaging biological dynamics in deep tissue

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