Abstract
BackgroundIn humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery: in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs. no rotation using ultrasound and semi-variogram analyses.Results3-D renditions of ultrasound images showed longitudinal echogenic sheets that matched with collagenous sheets seen in histological preparations. Rank correlations between serial 2-D ultrasound and corresponding histology images resulted in high positive correlations for semi-variogram ranges computed parallel (r = 0.79, p < 0.001) and perpendicular (r = 0.63, p < 0.001) to the surface of the skin, indicating concordance in spatial structure between the two data sets. Needle rotation caused tissue displacement in the area surrounding the needle that was mapped spatially with ultrasound elastography and corresponded to collagen bundles winding around the needle on histological sections. In semi-variograms computed for each ultrasound frame, there was a greater change in the area under the semi-variogram curve across successive frames during needle rotation compared with no rotation. The direction of this change was heterogeneous across subjects. The frame-to-frame variability was 10-fold (p < 0.001) greater with rotation than with no rotation indicating changes in tissue structure during rotation.ConclusionThe combination of ultrasound and semi-variogram analyses allows quantitative assessment of dynamic changes in the structure of human connective tissue in vivo.
Highlights
In humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions
The complementary techniques used in this study show that the laminar collagenous structures seen with ultrasound reorganized during rotation of an inserted needle
The combination of ultrasound and semi-variogram analysis used in this study is novel in biology
Summary
Connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. Modern understanding of complex systems suggests that, given these two types of interconnections, the dynamic responsiveness of fibroblasts within connective tissue may be affected by the structural characteristics of the collagenous network both locally and at a distance [15,16] Understanding these potentially important phenomena requires non-invasive measurements of both collagen network structure and cell function that can be performed in live animals or humans. A technique allowing quantitative evaluation of both superficial and deep connective tissue network structure may open up a new area of investigation in systems biology
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