Optoacoustic Imaging (Photoacoustic Imaging)

Optoacoustic Imaging: Frontier in Cancer Detection

Optoacoustic Imaging technique combines laser-induced ultrasound and optical imaging to visualize biological tissues. It captures high-resolution images of tissue structures, offering insights for medical diagnostics, cancer research, and vascular studies by revealing both anatomical and molecular information.
Image from Optoacoustic Imaging

Overview

Optoacoustic imaging, also known as photoacoustic tomography, is a cutting-edge imaging technique that combines the strengths of both optics and acoustics to provide high-resolution, deep-tissue imaging in biological systems. This revolutionary technology has garnered significant attention in the fields of medical diagnostics, preclinical research, and functional imaging. In this comprehensive article by Academic Block, we will examine the principles, instrumentation, applications, and future prospects of optoacoustic imaging, exploring how this innovative technique is reshaping our understanding of biological structures and functions.

Principles of Optoacoustic Imaging

Photoacoustic Effect: Optoacoustic imaging relies on the photoacoustic effect, a phenomenon where the absorption of laser light by tissue leads to the generation of acoustic waves. This process involves three key steps:

  • Absorption of Light: A short-pulsed laser is used to irradiate tissue. When the laser light is absorbed by endogenous chromophores (such as hemoglobin, melanin, or lipids) or exogenous contrast agents, it induces a rapid localized heating.
  • Thermal Expansion: The absorbed energy causes a rapid and transient increase in temperature, leading to thermoelastic expansion. This results in the generation of acoustic waves.
  • Acoustic Detection: Ultrasound transducers detect the generated acoustic waves, which are then used to reconstruct images that represent the distribution of light-absorbing structures in the tissue.

Image Formation: The acquired ultrasound signals are processed to create optoacoustic images. Various algorithms are employed for image reconstruction, such as time-domain reconstruction, frequency-domain reconstruction, and model-based reconstruction. These methods allow for the generation of high-resolution images that provide detailed information about the tissue's optical properties.

Instrumentation

  1. Laser System: A crucial component of optoacoustic imaging is the laser system, which provides the light source for photoacoustic excitation. Typically, pulsed lasers with wavelengths in the near-infrared (NIR) range are used to achieve deeper tissue penetration and minimize light scattering.

  2. Ultrasound Detection: Ultrasound transducers play a vital role in optoacoustic imaging by capturing the acoustic signals generated within the tissue. High-frequency transducers enable the detection of fine structures, while lower frequencies enhance the imaging depth.

  3. Image Reconstruction System: Advanced signal processing and image reconstruction algorithms are employed to convert the acquired signals into high-resolution optoacoustic images. Real-time imaging is essential for clinical applications, necessitating efficient and fast algorithms.

  4. Hybrid Imaging Systems: Optoacoustic imaging is often integrated with other imaging modalities, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), to provide complementary information and enhance diagnostic capabilities. These hybrid systems offer a comprehensive approach to imaging that combines anatomical and functional data.

Applications of Optoacoustic Imaging

  1. Cancer Imaging: One of the most promising applications of optoacoustic imaging is in the field of cancer detection and characterization. The technique can visualize hemoglobin distribution, offering insights into the tumor's vascularization and oxygenation status. Additionally, exogenous contrast agents can be employed to target specific molecular markers associated with cancer.

  2. Neuroimaging: Optoacoustic imaging has shown potential in neuroimaging, allowing researchers and clinicians to study the brain's structure and function with high spatial resolution. Its ability to image hemodynamic changes and cerebral blood flow provides valuable information for understanding neurological disorders and brain function.

  3. Cardiovascular Imaging: The imaging of blood vessels and the cardiovascular system is another important application of optoacoustic imaging. It can provide detailed information about vascular morphology, detect plaque formations, and assess blood oxygenation levels, contributing to the diagnosis and monitoring of cardiovascular diseases.

  4. Functional Imaging: Optoacoustic imaging enables functional imaging by capturing dynamic processes, such as blood flow and oxygenation changes, in real time. This is particularly valuable for understanding physiological and pathological processes in various tissues and organs.

  5. Preclinical Research: In preclinical research, optoacoustic imaging is extensively used to study disease models, drug responses, and biological processes in small animal models. The high resolution and non-invasive nature of the technique make it an invaluable tool for investigating various aspects of physiology and pathology.

Mathematical equations behind the Optoacoustic Imaging

Optoacoustic imaging, also known as photoacoustic imaging or tomography, involves several key mathematical equations that describe the fundamental principles of the technique. These equations relate to the photoacoustic effect, the acoustic wave equation, and the image reconstruction process. Here, we will explore these equations in more detail:

Photoacoustic Effect: The photoacoustic effect describes the generation of acoustic waves resulting from the absorption of pulsed laser light in biological tissue. The photoacoustic pressure (P(r,t)) can be expressed as:

P(r,t) = β ⋅ [ ∂I(r,t) / ∂t ] ;

Where:

  • P(r,t) is the photoacoustic pressure at position r and time t,
  • β is the photoacoustic conversion efficiency,
  • I(r,t) is the spatial and temporal distribution of the absorbed optical energy.

Acoustic Wave Equation: The acoustic wave equation governs the propagation of the generated photoacoustic waves within the tissue. In a homogeneous medium, the equation is given by:

2 P(r,t) − [ (1 / v2) (∂2P(r,t) / ∂t2) ] = −β (∂c(r) / ∂t) (∂I(r,t) / ∂t) ;

Where:

  • 2 is the Laplacian operator,
  • v is the speed of sound in the tissue,
  • c(r) is the speed of sound distribution in the tissue.

This equation accounts for the spatial distribution of the acoustic pressure and its temporal evolution.

Image Reconstruction: The goal of optoacoustic imaging is to reconstruct the spatial distribution of optical absorption within the tissue from the measured photoacoustic signals. A common method for image reconstruction is the back-projection algorithm. In its simplest form, the back-projection equation is given by:

I(r) = (−1 / β) ∇ ⋅ [ (1 / 4πv) ∫ P(r,t) r dt] ;

Where:

  • I(r) is the distribution of optical absorption,
  • is the gradient operator.

This equation integrates the measured photoacoustic signals over time and space to reconstruct the initial distribution of absorbed optical energy.

It's important to note that these equations represent simplified models, and in practice, additional factors such as acoustic attenuation, heterogeneity of tissue properties, and specific characteristics of the imaging system may be considered for more accurate modeling and image reconstruction.

Advantages and Challenges

Advantages

  • High Resolution: Optoacoustic imaging provides high-resolution images, allowing for detailed visualization of tissue structures and functional parameters.
  • Non-Invasiveness: Unlike some imaging modalities that require contrast agents or invasive procedures, optoacoustic imaging can be performed non-invasively, reducing patient discomfort and risk.
  • Functional Imaging: The technique allows for functional imaging, providing information about physiological processes such as blood flow, oxygenation, and molecular expression.
  • Versatility: Optoacoustic imaging is versatile and can be applied to various biological tissues and organs, making it a valuable tool in different medical fields.

Challenges

  • Depth Limitations: While optoacoustic imaging can achieve remarkable resolution, its penetration depth is limited, particularly in highly scattering tissues. Overcoming this challenge remains a focus of ongoing research.
  • Lack of Standardization: Standardization of imaging protocols and data analysis methods is essential for ensuring consistency and comparability across different imaging systems and studies.
  • Clinical Translation: While optoacoustic imaging has shown great promise in preclinical studies, its widespread clinical adoption requires further validation and optimization. This includes addressing issues related to imaging depth, real-time imaging capabilities, and clinical workflow integration.
  • Cost and Accessibility: The initial cost of optoacoustic imaging systems and the expertise required to operate them may pose challenges to widespread accessibility, particularly in resource-limited settings.

Future Directions

  1. Improving Imaging Depth: Research efforts are underway to enhance the imaging depth of optoacoustic imaging. This includes the development of advanced imaging technologies, such as multi-wavelength imaging and novel contrast agents, to overcome the limitations posed by tissue scattering.

  2. Standardization and Validation: To facilitate the clinical translation of optoacoustic imaging, efforts are being made to establish standardized imaging protocols, data analysis methods, and validation processes. This will ensure the reliability and reproducibility of results across different imaging systems and clinical settings.

  3. Hybrid Imaging Integration: The integration of optoacoustic imaging with other imaging modalities, such as ultrasound, CT, and MRI, is expected to increase in the coming years. This hybrid approach can provide comprehensive and complementary information, enhancing diagnostic accuracy and clinical utility.

  4. Clinical Applications: Ongoing clinical trials and studies are exploring the potential of optoacoustic imaging in various medical fields, including oncology, neurology, and cardiology. As more evidence accumulates, the technique is likely to find its place in routine clinical practice for disease diagnosis, monitoring, and treatment planning.

Final Words

Optoacoustic imaging represents a cutting-edge technology that combines the strengths of optics and acoustics to provide high-resolution, functional images of biological tissues. Its applications in cancer imaging, neuroimaging, cardiovascular imaging, and preclinical research highlight its versatility and potential impact on various medical disciplines. In this article we have seen that, while challenges such as limited imaging depth and the need for standardization persist, ongoing research and technological advancements are paving the way for the widespread clinical adoption of optoacoustic imaging. As the field continues to evolve, it holds great promise for revolutionizing medical imaging and improving our understanding of complex biological processes. Please provide you comments below, it will help us in improving this article. Thanks for reading!

This Article will answer your questions like:

+ What is optoacoustic imaging and how does it work? >

Optoacoustic imaging, also known as photoacoustic imaging, is an imaging technique that combines the principles of optics and acoustics to visualize tissues and organs. It works by illuminating tissues with short laser pulses, which are absorbed and then thermoelastically expand, generating ultrasound waves. These ultrasound waves are detected by transducers and used to reconstruct images that provide structural, functional, and molecular information about biological tissues.

+ How does optoacoustic imaging combine light and sound for medical diagnostics? >

Optoacoustic imaging combines light and sound by using pulsed laser light to generate ultrasound signals within tissues. The light energy is absorbed by tissues, leading to rapid heating and thermoelastic expansion, which produces ultrasound waves. These waves are then detected by transducers and converted into high-resolution images that reveal tissue morphology, blood oxygenation levels, and the presence of specific biomolecules. This dual modality provides complementary information not easily achievable by other imaging techniques, making optoacoustic imaging valuable for both clinical diagnostics and preclinical research.

+ What is the principle of optoacoustic imaging? >

Optoacoustic imaging combines optical and ultrasound techniques to visualize biological tissues. The principle involves illuminating tissue with pulsed laser light, which is absorbed by chromophores, leading to localized thermal expansion and the generation of ultrasound waves. These waves are detected and used to create high-resolution images that provide information about tissue structure and function, enabling applications in biomedical research, cancer detection, and monitoring therapeutic responses.

+ How does optoacoustic imaging provide functional and molecular information about tissues? >

Optoacoustic imaging provides functional and molecular information by detecting specific absorption spectra of molecules such as hemoglobin, melanin, and contrast agents. This allows assessment of tissue oxygenation levels, metabolic activity, and distribution of biomarkers associated with disease states. Functional information is derived from hemodynamic responses and tissue perfusion dynamics, while molecular specificity comes from spectroscopic analysis of optoacoustic signals. Combined, these capabilities enable precise localization and characterization of pathological changes at both macroscopic and microscopic scales.

+ What are the key components of an optoacoustic imaging system? >

An optoacoustic imaging system typically includes a pulsed laser source emitting near-infrared light, acoustic detectors (ultrasound transducers) for capturing generated ultrasound waves, data acquisition hardware, and sophisticated image reconstruction software. Additionally, optical components such as lenses and mirrors are used to deliver light to the tissue and collect the resulting optoacoustic signals. Advanced systems may integrate multi-wavelength capabilities for spectroscopic analysis and real-time imaging modalities for clinical applications.

+ What are the applications of photoacoustic imaging? >

Photoacoustic imaging has diverse applications in the medical field, including oncology for tumor detection and characterization, as well as vascular imaging to assess blood flow and oxygenation levels. It is also used in monitoring therapy responses and guiding interventions. Beyond clinical applications, photoacoustic imaging is employed in preclinical research to study disease mechanisms, drug delivery, and tissue engineering, demonstrating its versatility in advancing biomedical science.

+ How does optoacoustic imaging compare to other imaging techniques like MRI or ultrasound? >

Optoacoustic imaging offers advantages over MRI and ultrasound by providing high spatial resolution comparable to ultrasound and molecular specificity akin to MRI contrast-enhanced techniques. It excels in visualizing soft tissues, monitoring blood oxygenation, and detecting molecular markers without ionizing radiation. Compared to ultrasound, optoacoustic imaging achieves deeper tissue penetration and superior resolution, enabling detailed imaging of organs and structures located deep within the body. This makes it suitable for both superficial and deep tissue imaging applications in clinical diagnostics and preclinical research.

+ What is the difference between ultrasound and photoacoustic imaging? >

The primary difference between ultrasound and photoacoustic imaging lies in their underlying mechanisms. Ultrasound imaging utilizes high-frequency sound waves to create images based on the reflection of these waves from tissues. In contrast, photoacoustic imaging employs pulsed laser light, which generates ultrasound waves through thermal expansion. While ultrasound provides excellent real-time anatomical information, photoacoustic imaging offers enhanced contrast and functional insights by exploiting optical absorption properties of tissues.

+ What role does optoacoustic imaging play in cancer detection and characterization? >

Optoacoustic imaging plays a crucial role in cancer detection and characterization by visualizing tumor vasculature, assessing tumor oxygenation levels, and monitoring treatment responses non-invasively. It aids in early detection of small tumors, guiding biopsy procedures, and evaluating the efficacy of therapeutic interventions such as chemotherapy and photodynamic therapy. The ability to image molecular targets and assess metabolic changes enhances its utility in oncology, offering insights into tumor microenvironments and facilitating personalized treatment strategies.

+ How is optoacoustic imaging used in visualizing vascular structures and blood flow? >

Optoacoustic imaging visualizes vascular structures and blood flow by detecting hemoglobin-related signals that reflect the oxygenation state and perfusion dynamics of blood vessels. It provides high-resolution images of vascular networks, including arteries, veins, and capillaries, allowing assessment of blood flow patterns and vascular abnormalities associated with cardiovascular diseases, stroke, and peripheral vascular disorders. Real-time imaging capabilities enable dynamic monitoring of vascular responses to physiological stimuli and therapeutic interventions, supporting clinical decision-making in vascular medicine and surgical planning.

+ What are the advantages of photoacoustic imaging? >

Photoacoustic imaging offers several advantages, including high spatial resolution and the ability to visualize functional information about tissues. It allows for deep tissue imaging without ionizing radiation, making it safer for patients. The technique can differentiate between various tissue types based on their optical absorption characteristics, enabling enhanced contrast in images. Additionally, it is versatile, finding applications in cancer diagnostics, vascular imaging, and monitoring therapeutic effects in real-time.

+ What are the limitations and challenges of optoacoustic imaging technology? >

Challenges in optoacoustic imaging include limited depth resolution at greater tissue depths, variability in signal quantification due to tissue heterogeneity, and the need for complex image reconstruction algorithms. Scalability for clinical translation and standardization of imaging protocols pose additional challenges, along with the development of biocompatible contrast agents for molecular imaging. Improvements in hardware design, signal processing techniques, and multi-modal integration are addressing these challenges, aiming to enhance the clinical utility and reliability of optoacoustic imaging in diverse medical applications.

+ How do scientists interpret and analyze data obtained from optoacoustic imaging? >

Scientists interpret and analyze optoacoustic imaging data by reconstructing images based on detected ultrasound signals and correlating them with spectroscopic information. Image processing algorithms enhance contrast, remove noise, and visualize anatomical structures and functional parameters such as blood oxygenation levels and tissue perfusion dynamics. Quantitative analysis involves comparing signal intensities, spatial distributions, and temporal changes to assess disease states, monitor treatment responses, and validate imaging findings against histopathological or physiological data. Multi-parametric approaches integrate anatomical and molecular data, providing comprehensive insights into tissue microenvironments and pathophysiological processes.

+ What advancements have been made in optoacoustic imaging instrumentation and contrast agents? >

Advancements in optoacoustic imaging include the development of multi-wavelength imaging systems for spectroscopic analysis, ultrafast laser sources for real-time imaging, and high-resolution transducers for improved sensitivity and depth penetration. Contrast agents such as targeted nanoparticles and genetically encoded probes enable molecular imaging and specific biomarker detection, enhancing diagnostic accuracy and therapeutic monitoring. Integration with anatomical imaging modalities like MRI and CT expands clinical applications, while advancements in image reconstruction algorithms and data processing techniques improve image quality and quantitative analysis capabilities. Future developments aim to further enhance spatial resolution, expand imaging depth, and facilitate translation of optoacoustic imaging into routine clinical practice.

Hardware and software required for Optoacoustic Imaging (Photoacoustic Tomography)

Hardware Components:

Laser System:

  • Pulsed Laser: A laser system capable of producing short pulses, typically in the nanosecond range. This laser is used to irradiate the tissue and induce photoacoustic signals.
  • Tunable Wavelengths: Adjustable wavelengths in the near-infrared (NIR) range to optimize tissue penetration.

Ultrasound Transducer:

  • High-Frequency Transducer: Transducers with high-frequency capabilities for optimal resolution, especially for superficial imaging.
  • Array Configuration: Depending on the application, linear or array transducers may be used for different imaging requirements.

Data Acquisition System:

  • Analog-to-Digital Converters (ADCs): High-speed ADCs for converting analog photoacoustic signals into digital data.
  • Synchronization Hardware: Mechanisms for precise synchronization between laser pulses and data acquisition.

Optical Delivery System:

  • Optical Fibers or Light Delivery Mechanisms: Deliver laser pulses to the imaging region.

Imaging Chamber or Probe:

  • Optimized Probe Design: Depending on the imaging depth and application, a suitable probe or imaging chamber is required.

Positioning System:

  • Precise Positioning System: Allows accurate positioning and movement control of the imaging probe or sample.

Computing Hardware:

  • High-Performance Computing (HPC) System: Powerful computing resources, including CPUs and GPUs for real-time processing and reconstruction.

Cooling Systems:

  • Cooling Mechanisms: Cooling systems for laser sources and other components to prevent overheating.

Control and Interface Components:

  • User Interface Components: Control computer systems and graphical user interfaces (GUIs) for operating and monitoring the imaging system.

Software Components:

Control Software:

  • System Control Software: Software for controlling the laser system, ultrasound transducer, and other hardware components.

Data Acquisition Software:

  • Acquisition Control Software: Coordinates the acquisition of photoacoustic signals and synchronization with laser pulses.

Reconstruction Software:

  • Image Reconstruction Algorithms: Software implementing algorithms for reconstructing optoacoustic images from acquired data. This could include back-projection, model-based, or iterative reconstruction methods.

Image Processing Software:

  • Post-Processing Tools: Software for enhancing, visualizing, and analyzing reconstructed images.

Data Storage and Management:

  • Data Storage Systems: Software for managing and storing large volumes of imaging data.

Integration Software:

  • Hybrid Imaging Integration Software: If applicable, software for integrating optoacoustic imaging with other imaging modalities in a hybrid system.

Calibration Software:

  • Calibration Tools: Software for system calibration to ensure accuracy and reliability.

Safety Features:

  • Safety Monitoring Software: Features ensuring the safe operation of the imaging system.

User Interface:

  • Graphical User Interface (GUI): Provides a user-friendly interface for system control, monitoring, and setup.

System Integration Software:

  • Integration Software: Ensures proper communication and coordination between various hardware and software components in the imaging system.

Father of Optoacoustic Imaging (Photoacoustic Tomography)

Optoacoustic imaging, also known as photoacoustic imaging, has roots in the work of multiple researchers. However, the term “father” of optoacoustic imaging is often associated with Professor Paul L. Richards. In the 1970s, Richards conducted pioneering research in the field of photoacoustic phenomena and made significant contributions to the understanding and development of optoacoustic imaging techniques. His work laid the foundation for the application of photoacoustic principles in medical imaging.

Facts on Optoacoustic Imaging (Photoacoustic Tomography)

Principle of Operation: Optoacoustic imaging is based on the photoacoustic effect, where absorption of pulsed laser light by tissue results in the generation of acoustic waves. These waves can be detected and used to reconstruct images of the internal structures.

Hybrid Imaging Technique: It combines the high contrast of optical imaging with the high resolution and depth penetration of ultrasound imaging. This allows for imaging biological tissues at various depths with good spatial resolution.

Tissue Penetration: Optoacoustic imaging is well-suited for imaging deeper tissues, as near-infrared light is used for excitation. This allows penetration into biological tissues, making it applicable for imaging internal organs and structures.

Non-ionizing Radiation: Unlike some medical imaging modalities such as X-rays or CT scans, optoacoustic imaging uses non-ionizing radiation (laser light and ultrasound), which makes it safer for repeated imaging studies.

Functional and Molecular Imaging: Optoacoustic imaging can provide functional and molecular information about tissues. It allows visualization of tissue oxygenation, blood perfusion, and the distribution of specific molecules, making it valuable for studying physiological and pathological processes.

Multispectral Imaging: Optoacoustic imaging can capture multispectral data, enabling the assessment of tissue composition based on differences in optical absorption at various wavelengths. This can be used to distinguish between different tissue types.

Applications in Cancer Imaging: One of the prominent applications of optoacoustic imaging is in cancer imaging. It provides detailed images of tumors and their vasculature, aiding in early detection, characterization, and monitoring of treatment response.

Real-time Imaging Capability: Optoacoustic imaging has the potential for real-time imaging, allowing clinicians and researchers to observe dynamic processes such as blood flow and oxygenation changes during interventions or physiological studies.

Preclinical and Clinical Imaging: While initially developed and widely used in preclinical research, optoacoustic imaging is increasingly being translated to clinical applications. It holds promise for various medical fields, including oncology, cardiology, dermatology, and neurology.

Advancements and Research Areas: Ongoing research is focused on advancing optoacoustic imaging technologies, improving image reconstruction algorithms, and exploring new applications. Researchers are also working on the development of handheld and portable devices for clinical use.

Combination with Other Modalities: Optoacoustic imaging can be integrated with other imaging modalities such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) to provide complementary information and enhance overall diagnostic capabilities.

Clinical Trials and Commercial Systems: There are ongoing clinical trials exploring the use of optoacoustic imaging in various medical applications. Additionally, commercial optoacoustic imaging systems are becoming available for research and clinical use.

Academic References on Optoacoustic Imaging (Photoacoustic Tomography)

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  2. Ntziachristos, V. (2010). Going deeper than microscopy: the optical imaging frontier in biology. Nature methods, 7(8), 603-614.
  3. Wang, L. V., & Hu, S. (2012). Photoacoustic tomography: in vivo imaging from organelles to organs. Science, 335(6075), 1458-1462.
  4. Taruttis, A., Morscher, S., Burton, N. C., Razansky, D., & Ntziachristos, V. (2015). Fast multispectral optoacoustic tomography (MSOT) for dynamic imaging of pharmacokinetics and biodistribution in multiple organs. PloS one, 10(6), e0130289.
  5. Razansky, D., Baeten, J., & Ntziachristos, V. (2009). Sensitivity of molecular target detection by multispectral optoacoustic tomography (MSOT). Medical physics, 36(3), 939-945.
  6. Zhang, H. F., Maslov, K., & Wang, L. V. (2006). In vivo imaging of subcutaneous structures using functional photoacoustic microscopy. Nature protocols, 2(4), 797-804.
  7. Cox, B., Laufer, J. G., & Beard, P. C. (2012). The challenges for quantitative photoacoustic imaging. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 226(5), 331-348.
  8. Kim, C., Song, K. H., Gao, F., & Wang, L. V. (2010). Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats—volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging. Radiology, 255(2), 442-450.
  9. Ermilov, S. A., Khamapirad, T., Conjusteau, A., Leonard, M. H., Lacewell, R., Mehta, K., … & Oraevsky, A. A. (2009). Laser optoacoustic imaging system for detection of breast cancer. Journal of biomedical optics, 14(2), 024007.
  10. Niederhauser, J. J., Jaeger, M., Lemor, R., Weber, P., & Frenz, M. (2005). Combined ultrasound and optoacoustic system for real-time high-contrast vascular imaging in vivo. IEEE transactions on medical imaging, 24(4), 436-440.
  11. Dean-Ben, X. L., Fehm, T. F., & Razansky, D. (2016). Universal multispectral optoacoustic tomography (uMSOT) for high-contrast volumetric deep tissue imaging in real time. Nature Communications, 7, 12121.
  12. Heijblom, M., Piras, D., Xia, W., van Hespen, J. C. G., Klaase, J. M., van den Engh, F. M., … & Steenbergen, W. (2012). Visualizing breast cancer using the Twente photoacoustic mammoscope: What do we learn from twelve new patient measurements?. Optics express, 20(11), 11582-11597.
  13. Merčep, E., Jansen, K., Dam, P. V., Schaar, J. A., Hamersma, E., Giessen, E. B. V. D., … & Steenbergen, W. (2018). Real-time volumetric assessment of ablative margin by photoacoustic microscopy of tumor thermal expansion. Photoacoustics, 12, 63-72.
  14. Oraevsky, A. A., Jacques, S. L., Esenaliev, R. O., & Tittel, F. K. (1997). Laser-based optoacoustic imaging in biological tissues. Proceedings of the SPIE, 2979, 34-42.

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