Photoacoustic tomography (PAT), also known as optoacoustic tomography, is an imaging technique that integrates ultrasound and optical technologies to visualize biological tissues. It detects optical absorption contrast using the photoacoustic effect.1,2
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PAT produces high-resolution images in both the ballistic and diffusive optical regimes, as ultrasound scatters less than light in tissue. Its ability to perform multiscale imaging with a consistent contrast mechanism makes it valuable for bridging macroscopic and microscopic domains in the life sciences. The technique shows great potential for clinical practice and preclinical research.1,2
How Photoacoustic Tomography Works
PAT signals primarily originate from optical absorption. The generation of photoacoustic signals involves three key steps: light absorption by the object; conversion of the absorbed optical energy into heat, leading to an increase in temperature; and thermoelastic expansion, resulting in acoustic wave emission.1,3
For acoustic wave generation, thermal expansion must vary over time. This is achieved using either a continuous-wave laser with intensity modulation at a variable or constant frequency or a pulsed laser. In PAT, the imaging process often starts with the emission of a short laser pulse directed at biological tissue.1,3
As photons travel through the tissue, some are absorbed by biomolecules like cytochrome, melanin, water, lipids, deoxyribonucleic acid (DNA)/ribonucleic acid (RNA), and hemoglobin. The absorbed energy is then fully or partially converted into heat through nonradiative molecular relaxation.1,3
An ultrasonic transducer or transducer array detects the heat-induced pressure wave outside the tissue to create an image that maps the optical energy deposition within the tissue. PAT has 100% relative sensitivity to small changes in optical absorption, meaning that a specific percentage change in the optical absorption coefficient results in an equivalent change in the photoacoustic signal amplitude.1,3
In comparison, back-scattering-based confocal microscopy shows much lower sensitivity to optical absorption—approximately 6 % at 560 nm and 0.08 % at 800 nm in blood. Unlike fluorescence-based techniques, PAT can image nearly all molecules, whether fluorescent or non-fluorescent, as it does not rely on fluorescence emission, which often has a quantum yield of less than 100 %.1,3
Advantages of PAT
PAT offers several advantages, including high spatial resolution, deep tissue penetration, and the ability to provide both functional and structural information. To achieve deeper penetration, broader illumination schemes are used, while the spatial resolution is determined by the ultrasound transducer.1,3
The integration of optical excitation and ultrasonic detection makes PAT maximally sensitive to the rich optical absorption contrast of biological tissues. Thus, the technique is inherently suitable for neuronal and molecular imaging using exogenous contrast, as well as for molecular, metabolic, functional, and histologic imaging through endogenous contrast.1,3
PAT also offers greater penetration depth with scalable spatial resolution than optical microscopy, as biological tissue is significantly more transparent to sound than light, based on the scattering mean free path. 1,3
PAT is highly compatible with and complementary to other imaging modalities, such as ultrasound and optical imaging. PAT-enhanced multimodal imaging delivers rich complementary contrasts, enabling a more comprehensive understanding of biological phenomena.1,3
Clinical and Preclinical Applications of PAT
PAT has demonstrated significant potential for various medical applications, including tumor detection, vascular imaging, and treatment monitoring. Recently, substantial progress has been achieved in noninvasive breast cancer diagnosis using PAT.4,5
A recent advancement in PAT, known as single-breath-hold photoacoustic computed tomography (SBH-PACT), can capture a three-dimensional (3D) image of an entire breast within a single breath-hold or approximately 15 seconds. SBH-PACT uses a full-ring transducer array for acoustic detection and 1064 nm light for excitation.4
SBH-PACT's high detection sensitivity enables detailed visualization of breast tumors, holding significant potential for applications in clinical breast care. It distinguishes lesions from normal tissues by detecting local angiogenesis, identifying tumors in areas with higher blood vessel density.4 Tumors producing stronger photoacoustic signals can then be localized and further examined through analysis of the corresponding tumor-containing slice.4
Another major application of PAT is agent-free vascular imaging, which is crucial in diagnosing and monitoring various conditions, including skin diseases, peripheral vascular diseases, joint inflammation, and cancers such as thyroid, cervical, prostate, and colon.4,5
PAT offers a robust, noninvasive approach to peripheral vascular imaging, particularly for diabetic patients and chemotherapy monitoring. It complements existing clinical methods by enhancing spatiotemporal resolution, penetration depth, and contrast mechanisms. Additionally, PAT scanners using all-optical Fabry–Perot ultrasound sensors can generate highly detailed 3D microvascular images.4,6
A study in Nature Biomedical Engineering introduced a high-fidelity 3D PAT scanner that provides detailed, rapid in vivo 3D superficial vascular anatomy images within clinically acceptable acquisition times.6
The level of detail the scanner provides demonstrates its potential as a tool for clinical diagnosis, detection, and treatment monitoring of diseases like cancer and diabetes, which are associated with microcirculatory abnormalities.6
The combination of high image fidelity, fast acquisition speed, and design versatility positions the scanner for clinical translation in fields such as cardiovascular medicine, oncology, dermatology, and image-guided surgery.6
Recent Developments
Recent advancements in PAT technology have improved imaging speed, sensitivity, and portability. By integrating PAT with other imaging modalities and exploring its potential for personalized medicine, researchers aim to enhance medical diagnostics and treatment.4
A high-throughput photoacoustic imaging technique based on an ergodic relay (ER) was recently introduced in Nature Photonics. This method, called photoacoustic topography through an ER (PATER), uses a single-element detector to capture snapshot wide-field images.7
Due to its high imaging speed, PATER enables real-time imaging of pulse wave propagation in vivo. Additionally, PATER offers a cost-effective solution for high-throughput photoacoustic imaging, supporting the miniaturization of PAT systems for wearable and portable applications.7
Advances in small-animal PACT have also facilitated more extensive preclinical studies, particularly in scenarios requiring high sensitivity and spatiotemporal resolution.4 PAT could be integrated with conventional medical imaging modalities like magnetic resonance imaging and ultrasound imaging to obtain complementary information regarding the imaging tissue.8
Post-processing techniques, including feature extraction, image fusion, and image registration, can further enhance the value of PAT in multimodal imaging.8 By delivering detailed functional and molecular information, PAT shows promise for personalized medicine, potentially enabling treatments tailored to individual patients for improved precision and effectiveness.9
PAT: Current Impact and Future Directions
PAT is a powerful hybrid imaging technique that combines ultrasound and optical technologies. It offers high-resolution, deep tissue penetration, and the ability to provide both functional and structural information.
Recent advancements, such as SBH-PACT and PATER, have significantly improved imaging speed, sensitivity, and portability, enabling new clinical and preclinical applications.
PAT's integration with other imaging modalities and its potential for personalized medicine further enhance its clinical utility, particularly in cancer detection, vascular imaging, and treatment monitoring. The continuous evolution of PAT promises to revolutionize medical diagnostics and therapies.
References and Further Reading
- Duke University. (n.d.). Basics of photoacoustic imaging. [Online] Duke University. Available at https://photoacoustics.pratt.duke.edu/research/basics-photoacoustic-imaging (Accessed on 15 November 2024)
- Caltech. (n.d.). Photoacoustic Tomography. [Online] Available at https://coilab.caltech.edu/research/photoacoustic-tomography-pat (Accessed on 15 November 2024)
- Hysi, E., Moore, MJ., Strohm, EM., Kolios, MC. (2021). A tutorial in photoacoustic microscopy and tomography signal processing methods. Journal of Applied Physics. DOI: 10.1063/5.0040783, https://pubs.aip.org/aip/jap/article/129/14/141102/157380
- Wang, L. V., Li, L. (2021). Recent advances in photoacoustic tomography. BME Frontiers. DOI: 10.34133/2021/9823268, https://spj.science.org/doi/10.34133/2021/9823268
- Choi, W., Oh, D., Kim, C. (2020). Practical photoacoustic tomography: realistic limitations and technical solutions. Journal of Applied Physics. DOI: 10.1063/5.0008401, https://pubs.aip.org/aip/jap/article/127/23/230903/1062547
- Huynh, NT., et al. (2024). A fast all-optical 3D photoacoustic scanner for clinical vascular imaging. Nature Biomedical Engineering. DOI: 10.1038/s41551-024-01247-x, https://www.nature.com/articles/s41551-024-01247-x
- Li, Y. et al. (2020). Snapshot photoacoustic topography through an ergodic relay for high-throughput imaging of optical absorption. Nature Photonics. DOI: 10.1038/s41566-019-0576-2, https://www.nature.com/articles/s41566-019-0576-2
- Tang, K. et al. (2023). Advanced Image Post-Processing Methods for Photoacoustic Tomography: A Review. Photonics. DOI: 10.3390/photonics10070707, https://www.mdpi.com/2304-6732/10/7/707
- PREPRINT. Lucero, M. (2020). Towards Personalized Medicine: Photoacoustic Imaging Enables Companion Diagnosis and Targeted Treatment of Lung Cancer. Biological and Medicinal Chemistry. DOI: 10.26434/chemrxiv.11888214, https://www.researchgate.net/publication/339469728_Towards_Personalized_Medicine_Photoacoustic_Imaging_Enables_Companion_Diagnosis_and_Targeted_Treatment_of_Lung_Cancer
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