Soumik Saha Pranto, Yan Jing, Zhu Caigang
University of Kentucky, Department of Biomedical Engineering, Lexington, Kentucky, United States.
J Biomed Opt. 2025 Feb;30(Suppl 2):S23905. doi: 10.1117/1.JBO.30.S2.S23905. Epub 2025 Apr 23.
Precise imaging of tumor metabolism with its vascular microenvironment becomes emerging critical for cancer research because increasing evidence shows that the key attribute that allows a tumor to survive therapies is metabolic and vascular reprogramming. However, there are surprisingly few imaging techniques available to provide a systems-level view of tumor metabolism and vasculature on small animals for cancer discoveries.
We aim to develop a new multi-parametric microscope that can faithfully recapitulate metabolic and vascular changes with a wide field of view and microscope-level resolution to advance cancer-related investigations. To maximize the ease and accessibility of obtaining tissue metabolism and vasculature measurements, we aim to develop our new metabolic imaging tool with minimal cost and size, allowing one to easily quantify tissue metabolic and vascular endpoints together , advancing many critical biomedical inquiries.
We have combined fluorescence microscopy and dark-field microscopy in a re-emission geometry into one portable microscope to image the key metabolic and vascular endpoints on the same tissue site. The portable microscope was first characterized by tissue-mimicking phantoms. Then the multi-parametric system was demonstrated on small animals to image glucose uptake (using 2-NBDG) and mitochondrial membrane potential (using TMRE) along with vascular parameters (oxygen saturation and hemoglobin contents) of orthotopic tongue tumors .
Our phantom studies demonstrated the capability of the portable microscope for effective measurements of several key vascular and metabolic parameters with a comparable accuracy compared with our former reported benchtop spectroscopy and imaging systems. Our animal studies revealed increased glucose uptake and mitochondrial membrane potential along with reduced vascular oxygenation in tongue tumors compared with normal tongue tissues. The spatial analysis of metabolic and vascular images showed a more heterogeneous metabolic and oxygenation profile in tongue tumors compared with normal tongue tissues.
Our animal studies demonstrated the capability of our portable multi-parametric microscope for imaging the key metabolic and vascular parameters at the same tissue site with about one hour delay using an orthotopic tongue tumor model . Our study showed the potential of a portable functional microscope to noninvasively evaluate tumor biology using orthotopic tongue cancer models for future head and neck cancer research.
随着越来越多的证据表明肿瘤能够在治疗中存活的关键属性是代谢和血管重编程，对肿瘤代谢及其血管微环境进行精确成像在癌症研究中变得愈发关键。然而，令人惊讶的是，几乎没有成像技术能够在小动物身上提供肿瘤代谢和脉管系统的系统级视图，以用于癌症发现。
我们旨在开发一种新的多参数显微镜，它能够在宽视野和显微镜级分辨率下忠实地再现代谢和血管变化，以推进与癌症相关的研究。为了最大限度地提高获取组织代谢和脉管系统测量值的便捷性和可及性，我们旨在以最低的成本和尺寸开发我们的新代谢成像工具，使人们能够轻松地同时量化组织代谢和血管终点，推进许多关键的生物医学研究。
我们将荧光显微镜和暗场显微镜以再发射几何结构组合到一台便携式显微镜中，以对同一组织部位的关键代谢和血管终点进行成像。该便携式显微镜首先通过组织模拟体模进行表征。然后在小动物身上展示了该多参数系统，以成像原位舌肿瘤的葡萄糖摄取（使用2-NBDG）和线粒体膜电位（使用TMRE）以及血管参数（氧饱和度和血红蛋白含量）。
我们的体模研究证明了该便携式显微镜能够有效地测量几个关键的血管和代谢参数，其准确性与我们之前报道的台式光谱和成像系统相当。我们的动物研究表明，与正常舌组织相比，舌肿瘤中的葡萄糖摄取和线粒体膜电位增加，同时血管氧合减少。代谢和血管图像的空间分析表明，与正常舌组织相比，舌肿瘤中的代谢和氧合分布更加不均匀。
我们的动物研究证明了我们的便携式多参数显微镜能够使用原位舌肿瘤模型在大约一小时的延迟后对同一组织部位的关键代谢和血管参数进行成像。我们的研究显示了便携式功能显微镜在使用原位舌癌模型无创评估肿瘤生物学方面的潜力，可为未来的头颈癌研究提供帮助。
