Technical development of photoacoustic microvascular imaging
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Long, Xing
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Abstract
The vascular system is essential for oxygen and nutrient delivery to cells and organs while removing metabolic waste products. Among vascular network, arterioles and venules in the microvasculature act as crucial connectors between capillary networks and larger arteries and veins. Their regulatory functions and states significantly impact metabolism and physiological processes. Microvascular dysfunction often signals early stages of vascular diseases. Visualizing and monitoring microvessel morphology, structure, and hemodynamic changes are vital for early disease diagnosis and prognosis evaluation. However, the diameter of subcutaneous microvessels ranges from tens to more than 100 μm, and existing medical imaging techniques are not yet capable to provide high-resolution, high-contrast, noninvasive, label-free functional imaging of subcutaneous microvessels.
Photoacoustic (PA) imaging (PAI) technology combines the optical contrast of light absorption with the deep penetration depth of ultrasound (US), offering promise in biomedical imaging. Compared with other vascular imaging techniques, PAI has unique advantages and demonstrates great potential for noninvasive subcutaneous microvascular imaging. However, existing PA microvascular imaging has the limitations of insufficient imaging resolution and speed for clinical applications, and conventional opaque piezoelectric transducers affect the illumination of excitation light in photoacoustic microscopy (PAM) microvascular imaging of small animals. This thesis addressed the need for high-resolution three-dimensional (3D) microvascular imaging in clinical and preclinical studies by developing various PA microvascular imaging techniques and exploring future non-contact vascular imaging methods. Key research contents and innovations include:
(1) The use of a high-frequency linear array system and image processing algorithms significantly improves the speed and resolution of PA/US dual-modality imaging, enabling rapid visualization and functional imaging of human subcutaneous microvessels. Traditional PA array systems typically achieve resolutions of 300 μm or greater, limiting their effectiveness in microvascular imaging. Although PAM systems offer high resolution, their imaging duration is prolonged, impeding clinical utility. This study introduced skin surface PA signals removal and optical fluence compensation algorithms based on a high-frequency US linear array system, enabling high-resolution 3D PA/US visualization and functional quantitative imaging of human subcutaneous microvessels. Achieving an axial spatial resolution of 80 μm, the single-wavelength imaging time is under 39 s for a 30 mm × 23 mm area. Moreover, vascular occlusion experiments simulated vascular-related diseases, comprehensively demonstrating 3D microvascular hemodynamics process. This research underscores the clinical significance of high-resolution 3D subcutaneous microvascular PAI, promising early diagnosis and prognostic evaluation of vascular diseases.
(2) A wide bandwidth transparent ultrasound transducer (TUT) based on a new matching layer material and thickness design method was proposed to realize PA subcutaneous microvascular imaging with high axial resolution. Due to the opaque properties of traditional piezoelectric US transducers, it leads to complex system design and the difficulty to co-align optical and acoustic beam paths in PAM systems, bringing difficulty in small animal PA microvascular imaging. This study proposed the use of polymethyl methacrylate as the matching layer material, along with a universal matching layer thickness design method, suitable for bonding processes in the manufacturing of high-performance TUTs, which can enhance the bandwidth of transducer to be more than 50% at a center frequency of 20 MHz, surpassing previous TUT bandwidths reported at published time. Furthermore, a compact PAM system utilizing this TUT achieves a high axial resolution of 111 μm and demonstrates high-contrast, high-resolution PA imaging of subcutaneous microvessels in small animals. This research contributes advancements in detector technology, design, and manufacturing processes for high-resolution subcutaneous microvascular imaging based on TUTs.
(3) A non-contact, wide bandwidth US sensing technique based on a homodyne Mach-Zehnder interferometer (MZI) was developed, upon which a non-contact PAI system was built. Non-contact US/PA holds significant value for specific patient groups (e.g., those with skin trauma, intraoperative brain imaging) and for brain microvascular imaging of freely moving animals. However, previous studies mainly relied on commercial laser doppler vibrometer with limited bandwidths unsuitable for clinical requirements. This study explored a US detection method based on a homodyne interferometer system, achieving a wide bandwidth of 1-8.54 MHz (-6 dB), a marked improvement over reported MZI-based system. Additionally, a phase correction method was proposed to address inherent phase uncertainty. Phantom experiments further validated the robust imaging performance of the system.
In summary, this thesis focuses on advancing noninvasive PA microvascular imaging technology for clinical and periclinal scientific research, aiming to improve the diagnosis, treatment, and understanding of vascular-related diseases.
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2024-06-26
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Dissertation