Mapping Organizational Changes of Fiber‐Like Structures in Disease Progression by Multiparametric, Quantitative Imaging

Abstract

With the progression of diseases, modified cell–matrix interactions have major effects not only upon key cellular functions but also upon the structure of extracellular matrix and vasculature, which are two of the most prevalent fiber‐like structures in biological tissues. Unfortunately, quantitative approaches to assessing these structural changes are lacking. Herein, a multiparametric imaging system is established to resolve subtle organizational changes of collagen fibers and vasculature in disease progression. The pixel‐wise, automated waviness (paWav) is developed as a novel biomarker, and a multimodal analysis system combining paWav with orientation and alignment assessments is constructed. Aggregation‐induced emission luminogens (AIEgens) with second near‐infrared excitation or emission are developed for in vivo deep‐penetration vasculature imaging. The organization remodeling of cortical blood vessels in stroke in marmosets is quantitatively characterized using biologically excretable AIE dots that highlight the clinical translation potential, and a distance dependence law in vessel morphological remodeling is identified. Finally, the multiparametric analysis relying completely on collagen fiber signatures successfully differentiates cancerous from normal pancreatic tissues using a predictive classification approach. Collectively, the combined use of these structural changes in fibrillar tissue components may enable a better understanding of cell–matrix interactions in pathogenesis and identification of new potential treatment targets.

Aggregation-Induced Emission (AIE), Life and Health

“…Centimeter-deep and three-photon fluorescence NIR-II vascular imaging in nonhuman primates has also been realized. , Further, a series of quantitative approaches have been developed to assess the structural changes of deep vessels using biocompatible AIE dots . The morphological changes and organization remodeling of cortical blood vessels in marmosets during stroke have been fully and accurately analyzed. , …”

Mapping the 3D remodeling of the extracellular matrix in human hypertrophic scar by multi-parametric multiphoton imaging using endogenous contrast

“…The general process of MFM analysis is shown in Fig. 1 C. Based on the voxel-wise 3D orientation, directional variance and waviness, quantified in a truly 3D context, were calculated to measure the fiber alignment and bending degree [ [41] , [42] , [43] , [44] ], with both metrics ranging from 0 to 1. For directional variance, a lower variance value corresponded to more highly aligned fibers while a higher readout revealed more random fiber alignment.…”

“…Based on voxel-wise quantities, we were able to generate color-coded maps to visually display each metric. Algorithm details of these metrics mentioned above could be found in our previous study [ [40] , [41] , [42] , [43] , [44] ] and all the calculations were performed using MATLAB software.…”

“…The weighted vector summation algorithm proposed in our previous study enabled highly-accurate, truly 3D characterization of spatial orientation for fiber-like structures with a high sensitivity [ 40 ]. Based on orientation information, we further proposed optical metrics, named directional variance and waviness, respectively, as quantitative measures of alignment and bending degree of fibers, and applied them to mapping physiological and pathological functions of collagen fibers in articular cartilage, mammary glands, breast tissues, ovarian tissues and pancreas, in the context of diseases including osteoarthritis and cancer [ [41] , [42] , [43] , [44] ]. Besides, we developed an algorithm for the quantification of morphologically localized distribution of fiber-like structures, termed local coverage, which provided new insights into the spatial organization of fibrous tissues [ 45 ].…”

Mapping variation of extracellular matrix in human keloid scar by label-free multiphoton imaging and machine learning

“… 19 , 20 In addition, alterations in morphology and organization of collagen and elastin fibers, the major components of the ECM, are closely associated with physiologic and pathologic status of biological tissues. 21 – 25 Compared with traditional pathological methods, multiphoton imaging technology has great benefits in simplifying sample preparation. In the pathological method, it requires fixing the tissue sections with paraffin and staining them.…”