Photoacoustic imaging (PAI) is a non-invasive imaging technique that combines the principles of optical and ultrasound imaging to visualize internal biological structures at high spatial resolution. The main principle of PAI consists of the instantaneous thermal expansion of light absorbers caused by pulsed laser illumination and the detection of the resulting ultrasonic signals. The major characteristics of PAI, such as its sensitivity to optically absorptive targets (e.g., hemoglobin (Hb) and melanin), centimeters-deep imaging depth, and non-invasiveness, make it particularly effective in the diagnosis of skin diseases including cancers, inflammatory diseases, and vascular abnormalities.
Recently, Prof. Wonseok Choi from the Catholic University of Korea, College of Medicine, and Prof. Chulhong Kim from Pohang University of Science and Technology (POSTECH), along with the PhD students Junho Ahn and Minseong Kim from POSTECH, focused on the development of PAI for skin diseases and published a review paper titled "In vivo multi-scale clinical photoacoustic imaging for analysis of skin vasculature and pigmentation: a comparative review" in Advanced Imaging. This review offers a comprehensive overview of various modalities of PAI – microscopy, mesoscopy, and tomography – applied for clinical skin analysis. Further, these techniques are classified according to the imaging target, melanin and vasculature in the skin. We compare the imaging features and findings from the three PAI modalities and provide guidance for the selection of proper modality for clinical skin analysis according to the spatial resolution, imaging depth, and the field-of-view (FOV).
Conventional diagnostic tools for skin diseases include skin biopsies and optical or ultrasound (US) imaging, but these methods may suffer from limitations such as invasiveness, subjective evaluation, or low sensitivity. Skin biopsy for histological examination is often the gold standard for diagnosing many skin diseases, but it leaves a wound and can be impractical for assessing large lesions. Optical imaging such as photography or fluorescence imaging (i.e., Wood's lamp) can be performed in vivo to visually evaluate the color, size, or boundary of the skin lesions, but it can only assess superficial skin features and usually relies on subjective visual interpretation. US imaging can image centimeters depth into the tissue but lacks the sensitivity to visualize pigmentation or microvascular structures effectively. PAI is non-invasive, has a high spatial resolution, and is sensitive to Hb and melanin due to their strong light absorption; therefore, the method can effectively overcome these limitations of conventional methods. PAI can visualize the microvascular structure and melanin distribution below the skin surface with high contrast and can provide quantitative evaluation of these features to enable distinction between lesions of different skin diseases.
An overview of the photoacoustic imaging modalities for clinical skin imaging
Generally, PAI is categorized into three modalities: photoacoustic microscopy (PAM), which uses a focused laser and a focused US detector to achieve the finest spatial resolution at shallow depths; photoacoustic mesoscopy (PAMes), which uses an unfocused laser and a high-frequency focused US to achieve high resolution and less superficial imaging depth; and photoacoustic tomography (PAT), which uses an unfocused (diffused) laser and multiple low-frequency unfocused US transducers (i.e., a US transducer array) to achieve deep imaging depth but low spatial resolution. The high spatial resolution of PAM allows precise separation of each skin layer up to the superficial dermal layer and enables detailed delineation of the vasculature and melanin. PAMes can identify and analyze the structures up to deep dermal layers with a slightly degraded spatial resolution. PAT can image at a depth much deeper than the subcutaneous tissue and has a wider FOV than the other two modalities. It can show larger vessels at greater depths than the other modalities and can depict the melanin in a whole lesion across multiple layers of the skin.
Performance tradeoffs among the spatial resolution, imaging depth, and the FOV of various PAI modalities
In the papers reviewed here, both imaging depth and lateral FOV showed a trade-off relationship with spatial resolution. Least squares line fitting showed the general tradeoff that "imaging depth ≈ 92.6 × spatial resolution" and "lateral FOV ≈ 236 × spatial resolution". These relations can provide guidance on selecting an appropriate PAI modality for the skin imaging application of interest, depending on the desired precision and the size of the target.
Overall, PAI technology can diagnose human skin non-invasively and potentially meet a variety of needs in dermatology such as staging, progression, and treatment monitoring. PAI also provides quantifiable metrics by analyzing the PA signal amplitudes that represent Hb or melanin contents observed in various scales using PAM, PAMes, or PAT. By adopting a fit-for-purpose PAI system, dermatologists will be able to effectively diagnose and test skin diseases, and reduce the number of repetitive treatments.
