Abstract
Functional intestinal imaging holds importance for the diagnosis and evaluation of treatment of gastrointestinal diseases. Currently, preclinical imaging of intestinal motility in animal models is performed either invasively with excised intestines or noninvasively under anesthesia, and cannot reveal intestinal dynamics in the awake condition. Capitalizing on near-infrared optics and a high-absorbing contrast agent, we report the Trans-illumination Intestine Projection (TIP) imaging system for free-moving mice. After a complete system evaluation, we performed in vivo studies, and obtained peristalsis and segmentation motor patterns of free-moving mice. We show the in vivo typical segmentation motor pattern, that was previously shown in ex vivo studies to be controlled by intestinal pacemaker cells. We also show the effects of anesthesia on motor patterns, highlighting the possibility to study the role of the extrinsic nervous system in controlling motor patterns, which requires unanesthetized live animals. Combining with light-field technologies, we further demonstrated 3D imaging of intestine in vivo (3D-TIP). Importantly, the added depth information allows us to extract intestines located away from the abdominal wall, and to quantify intestinal motor patterns along different directions. The TIP system should open up avenues for functional imaging of the GI tract in conscious animals in natural physiological states.
Highlights
Functional intestinal imaging holds importance for the diagnosis and evaluation of treatment of gastrointestinal diseases
This study introduces Trans-illumination Intestine Projection (TIP) imaging, which we have developed the intestinal imaging system for free-moving mice (2D-TIP, Fig. 1a; left and Supplementary Fig. 1) and the 3D light-field-based intestinal imaging system (3D-TIP, Fig. 1a; right)
At different time points post gavage, spatial-temporal maps of the intestine clearly showed the transition of motor patterns over time after filling of the stomach, from peristalsis in the proximal intestine followed by segmentation in the remainder of the intestine to facilitate absorption
Summary
Functional intestinal imaging holds importance for the diagnosis and evaluation of treatment of gastrointestinal diseases. Many studies used mice to uncover the mechanims underlying intestinal motility involving the nervous systems and intestinal pacemaker activities[6,7,8] Invasive methods, such as in vitro imaging modalities of intestine[9,10], have been extensively used. 2D-TIP enables the visualization of peristalsis and segmentation motor patterns of free-moving mice, which has never been reported before. This unique imaging ability of 2D-TIP allows the in vivo demonstration that the anesthetized mice exhibited a much slower intestinal motility rate than the awake mice, highlighting its ability to study central nervous system regulation. We anticipate that TIP method will open up more avenues for functional imaging of the GI tract in animal models
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