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.

中文翻译：

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通过无创光声显微活检对皮肤血管病变进行定量和解剖成像

无创获取深层组织精细结构的能力非常有价值，但仍然是一个挑战。在这里，开发了一种光声显微活检 (PAMB) 将可切换空间尺度光激发与单元素深度分辨声学检测模式相结合，有效地协调了空间分辨率和穿透深度，以可视化皮肤分层和发色团结构直至网状结构。真皮深度，横向分辨率为 1.5 至 104 μm，轴向分辨率为 34 至 57 μm。PAMB 获得了表皮内色素分布和深层真皮组织血管模式的解剖成像，无需外源性造影剂即可量化血管病变的形态异常。健康皮肤和疤痕皮肤的特点，并且首先通过 PAMB 显示的多层成像精确显示了葡萄酒色斑 (PWS) 皮肤中真皮血管系统的异常改变。此外，PWS的定量血管参数评估是通过174名患者的详细临床PAMB数据进行的，揭示了不同皮肤类型之间的明显差异。PAMB 捕获毛细血管环深度、直径和血管容积的 PWS 变化，从而可以对 PWS 的严重程度进行客观的临床评估。所有结果表明PAMB可以无创地提供深入真皮皮肤的血管活检和新指标，对及时评估皮肤病的病理类型和治疗反应具有重要意义。这为皮肤血管病的无标记和非侵入性活检开​​辟了新的视角。