Indocyanine Green Fluorescence Imaging for Evaluation of Uterine Blood Flow in Cynomolgus Macaque

Abstract

BackgroundUterine blood flow is an important factor in uterine viability, but the number of blood vessels required to maintain viability is uncertain. In this study, indocyanine green (ICG) fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque.MethodsThe uterus of a female cynomolgus macaque was cut from the vaginal canal to mimic a situation during trachelectomy or uterine transplantation surgery in which uterine perfusion is maintained only with uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed using ICG fluorescence imaging under conditions in which various nutrient vessels were selected by clamping of blood vessels. A time-intensity curve was plotted using imaging analysis software to measure the Tmax of uterine perfusion for selected blood vessel patterns. Open surgery was performed with the uterus receiving nutritional support only from uterine vessels on one side. The size of the uterus after surgery was monitored using transabdominal ultrasonography.ResultsThe resulting time-intensity curves displayed the average intensity in the regions of the uterine corpus and uterine cervix, and in the entire uterus. Analyses of the uterine hemodynamics in the cynomolgus macaque showed that uterine vessels were significantly related to uterine perfusion (P = 0.008), whereas ovarian vessels did not have a significant relationship (P = 0.588). When uterine vessels were clamped, ovarian vessels prolonged the time needed to reach perfusion maximum. Postoperative transabdominal ultrasonography showed that the size of the uterus was not changed 2 months after surgery, with recovery of periodic menstruation. The cynomolgus macaque has got pregnant with favorable fetus well-being.ConclusionUterine vessels may be responsible for uterine blood flow, and even one uterine vessel may be sufficient to maintain uterine viability in cynomolgus macaque. Our results show that ICG fluorescence imaging is useful for evaluation of uterine blood flow since this method allows real-time observation of uterine hemodynamics.

Recent advances in the molecular mechanisms of Mayer-Rokitansky-Küster-Hauser syndrome

“…Uterine blood flow is significant in uterine viability, therefore two technical proedures were examined in the cynomolgus monkeys. The first method was indocyanine green (ICG) fluorescence imaging for evaluation of uterine blood flow (37,38). ICG fluorescence imaging, an angiographic technique that is simple to use and minimally invasive, enabled intraoperative real-time evaluation of uterine hemodynamics.…”

“…The second method involves use of the ovarian vein rather than the uterine vein as an anastomosis blood vessel (38). The ovarian vein is a thick vessel that runs along the upper part of the pelvis, and previous reports demonstrate that the ovarian vein may contribute to drainage of the uterus to a great extent (37)(38)(39)(40)(41). The vascular anastomosis with larger diameter leads to less complicated surgery, and the warm ischemic time is effectively reduced (39).…”

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“…26,27 Fluorescence imaging is used during surgery to assess patency of blood vessels and ureters. 28 Near-infrared (NIR) fluorescence (700 to 900nm) is often preferred for deep tissue imaging due to its higher depth of penetration and lower background fluorescence. 25,28 However, NIR fluorescence is invisible to the human eye, and emitted light levels are typically low for the human eye to see, requiring camera-based detection.…”

“…28 Near-infrared (NIR) fluorescence (700 to 900nm) is often preferred for deep tissue imaging due to its higher depth of penetration and lower background fluorescence. 25,28 However, NIR fluorescence is invisible to the human eye, and emitted light levels are typically low for the human eye to see, requiring camera-based detection. Clinical optical imaging systems typically consist of highly sensitive, scientific digital cameras with appropriate illumination source and optical filters for fluorescence detection.…”

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“…1,2 Fluorescence imaging is used during surgery to assess patency of blood vessels and ureters. 3 Near-infrared (NIR) fluorescence (700 to 900 nm) is often preferred for deep tissue imaging due to its higher depth of penetration and lower background fluorescence. 1,4 However, NIR fluorescence is invisible to the human eye, and emitted light levels are typically low for the human eye to see, requiring camera-based detection.…”