680 - Photoacoustic imaging to detect intestinal tissue oxygenation in a translational nonhuman primate model

Publication Number: 1657.680

Sarah N. Cilvik, Wake Forest Baptist Health - Brenner Children's Hospital, Winston-Salem, NC, United States; Paulina Wright, Wake Forest School of Medicine of Wake Forest Baptist Medical Center2, Winston-Salem, NC, United States; Victoria Weis, Wake Forest University School of Medicine, Winston Salem, NC, United States; Jared A. Weis, Wake Forest University School of Medicine, Winston-Salem, NC, United States

Background: Gastrointestinal complications are common among premature and growth-restricted infants due to underdeveloped vasculature, difficulty regulating oxygen delivery, and increased oxygen requirement from high nutrient demand and ongoing intestinal growth. This mismatch in oxygen supply and demand in the intestines can lead to reduced nutrient absorption, disruption of barrier function, and severe complications such as necrotizing enterocolitis. At present, few tools exist to assess intestinal oxygenation in real time.

Objective: Photoacoustic imaging (PAI) combines ultrasound and laser optical excitation to visualize tissue oxygenation. The objective of our translational study was to evaluate the feasibility and utility of intestinal PAI in a juvenile nonhuman primate model that is the equivalent size of a low birthweight human infant ( < 2.5kg). Furthermore, we sought to test the hypothesis that offspring from pregnancies complicated by hypertension or fetal growth restriction (FGR) would have lower intestinal oxygenation compared to offspring from healthy pregnancies.

Design/Methods: We selected 12 male vervet monkeys (Chlorocebus aethiops sabaeus), approximately 1-2 years old with body weight 1.5-2.5kg, in three cohorts: offspring from healthy (n=4), hypertensive (n=4), or FGR pregnancies (n=4). We anesthetized monkeys with isoflurane, then used an iThera MSOT Acuity scanner to acquire ultrasound and PAI data in four locations across the abdomen visualizing the intestines. We conducted scans twice: first while breathing 100% oxygen and again on 21% oxygen. We drew regions of interest to indicate the intestine in each scan and recorded mean intestinal oxygen saturation (sO2) for each animal.

Results: Intestinal sO2 was decreased in control animals breathing 21% compared to 100% oxygen (53.74±2.04% vs 57.16±1.20%, p< 0.01, Fig 1), validating the sensitivity of PAI to detect changes in intestinal tissue oxygenation. Additionally, intestinal sO2 was lower in FGR offspring compared to healthy controls breathing 100% oxygen (53.21±3.17% vs 57.16±1.20%, p< 0.05, Fig 2&3).

Conclusion(s): PAI is sensitive to detect changes in intestinal oxygenation during the oxygen reduction challenge in this translational NHP model. Furthermore, FGR offspring showed alterations in oxygen delivery beyond 1 year of age, likely reflective of impaired intestinal vascular development. These findings provide strong evidence that adverse pregnancies have lasting consequences on GI physiology, while also highlighting the feasibility of PAI as a non-invasive imaging method to assess intestinal oxygenation in a low birthweight population.

Figure 1. PAI oxygen reduction challenge.
Intestinal tissue sO2 of control NHPs (n=4) breathing 100% oxygen versus 21% oxygen shows a significant reduction in sO2 at 21% oxygen, validating the sensitivity of PAI for detecting physiologically relevant changes in intestinal tissue oxygenation. ** denotes p<0.01 using a paired t-test.

Figure 2. PAI of intestinal tissue oxygenation in NHP offspring of healthy (control) vs unhealthy (hypertensive, FGR) pregnancies.
FGR NHPs (n=4) breathing 100% oxygen show significantly lower sO2 compared to controls (n=4). * denotes p<0.05 using a one-way ANOVA with post-hoc Fisher's LSD.

Figure 3. Representative ultrasound (US) and PAI sO2 images from control and FGR NHPs.
Color scale provided to the right of the PAI images, with darkest red representing 100% sO2 and darkest blue representing 0% sO2. Scale bar = 5mm.