Abstract
The ability to noninvasively acquire the fine structure of deep tissues is highly valuable but remains a challenge. Here, a photoacoustic microscopic biopsy (PAMB) combined switchable spatial-scale optical excitation with single-element depth-resolved acoustic detection mode was developed, which effectively coordinated the spatial resolution and the penetration depth for visualizations of skin delamination and chromophore structures up to reticular dermis depth, with the lateral resolution from 1.5 to 104 μm and the axial resolution from 34 to 57 μm. The PAMB obtained anatomical imaging of the pigment distribution within the epidermis and the vascular patterns of the deep dermal tissue, enabling quantification of morphological abnormalities of angiopathy without the need for exogenous contrast agents. The features of healthy skin and scar skin, and the abnormal alteration of dermal vasculature in port wine stains (PWS) skin were first precisely displayed by PAMB-shown multi-layered imaging. Moreover, the quantitative vascular parameters evaluation of PWS were carried out by the detailed clinical PAMB data on 174 patients, which reveals distinct differences among different skin types. PAMB captured the PWS changes in capillary-loop depth, diameter, and vascular volume, making it possible to perform an objective clinical evaluation on the severity of PWS. All the results demonstrated the PAMB can provide vascular biopsy and new indexes deep into the dermal skin noninvasively, which should be meaningful to timely evaluate the pathological types and treatment response of skin diseases. This opens up a new perspective for label-free and non-invasive biopsies of dermal angiopathy.
Highlights
Detailed visualisation of the external and internal structures of tissue is always the key to perform a comprehensive examination and make an accurate diagnosis [1,2,3]
In terms of the pathological features and the clinical demand of skin diseases, in this paper, we developed a noninvasive photoacoustic microscopic biopsy (PAMB) system attached with a featured photoacoustic index and a clinical application scheme by using an adjustable confocal opto-sono objective
photoacoustic microscopy (PAM) opens a new chapter in the morphological examination of pigmented and vascular dermatosis as it can improve the accurate diagnoses of skin disease and can be used to quantitatively evaluate the curative effect of treatment in clinical practice and studies [46,47,48,49,50,51,52,53,54,55,56]
Summary
Detailed visualisation of the external and internal structures of tissue is always the key to perform a comprehensive examination and make an accurate diagnosis [1,2,3]. Despite many years of development, it remains a challenge to visualise the internal fine structure of skin tissue with high spatial resolution, deep penetration, and strong contrast in a non-invasive manner [6,7,8]. In view of the limitations of current diagnostic techniques, clinicians face great difficulties in making accurate classifications, optimising therapeutic regimens, and quantifying and evaluating therapies for skin diseases, such as port wine stains (PWS) – A kind of congenital and non-self-healing dermal vascular malformations with a high incidence of 3%0-5%0 [15], gradually expands with age and deteriorates into deep tissue infiltration. Since 1980s, cryotherapy, intense pulsed laser therapy and photodynamic therapy have been used in the clinical treatment of this disease, but so far, the complete cure rate of PWS is still less than 20% [16], which mainly lies in the inability to non-invasively identify the microvessels (tens of microns in diameter) in the lesion dermis in-situ, and to accurately control the dose and duration of treatment, often leading to longtime treatment or ineffective treatment
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