Maternal and fetal cardiometabolic recovery following ultrasound-guided high-intensity focused ultrasound placental vascular occlusion

Author:

Shaw Caroline J.12ORCID,Rivens Ian3ORCID,Civale John3ORCID,Botting Kimberley J.14ORCID,Allison Beth J.1ORCID,Brain Kirsty L.1,Niu Y.14ORCID,ter Haar Gail3ORCID,Giussani Dino A.14ORCID,Lees Christoph C.25ORCID

Affiliation:

1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK

2. Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK

3. Joint Department of Physics, Institute of Cancer Research, Sutton SM2 5NG, UK

4. Cardiovascular Strategic Research Initiative, University of Cambridge, Cambridge, UK

5. Department of Obstetrics and Gynaecology, University Hospitals Leuven, 3000 Leuven, Belgium

Abstract

High-intensity focused ultrasound (HIFU) is a non-invasive method of selective placental vascular occlusion, providing a potential therapy for conditions such as twin–twin transfusion syndrome. In order to translate this technique into human studies, evidence of prolonged fetal recovery and maintenance of a healthy fetal physiology following exposure to HIFU is essential. At 116 ± 2 days gestation, 12 pregnant ewes were assigned to control ( n = 6) or HIFU vascular occlusion ( n = 6) groups and anaesthetized. Placental blood vessels were identified using colour Doppler ultrasound; HIFU-mediated vascular occlusion was performed through intact maternal skin (1.66 MHz, 5 s duration, in situ I SPTA 1.8–3.9 kW cm −2 ). Unidentifiable colour Doppler signals in targeted vessels following HIFU exposure denoted successful occlusion. Ewes and fetuses were then surgically instrumented with vascular catheters and transonic flow probes and recovered from anaesthesia. A custom-made wireless data acquisition system, which records continuous maternal and fetal cardiovascular data, and daily blood sampling were used to assess wellbeing for 20 days, followed by post-mortem examination. Based on a comparison of pre- and post-treatment colour Doppler imaging, 100% (36/36) of placental vessels were occluded following HIFU, and occlusion persisted for 20 days. All fetuses survived. No differences in maternal or fetal blood pressure, heart rate, heart rate variability, metabolic status or oxygenation were observed between treatment groups. There was evidence of normal fetal maturation and no evidence of chronic fetal stress. There were no maternal injuries and no placental vascular haemorrhage. There was both a uterine and fetal burn, which did not result in any obstetric or fetal complications. This study demonstrates normal long-term recovery of fetal sheep from exposure to HIFU-mediated placental vascular occlusion and underlines the potential of HIFU as a potential non-invasive therapy in human pregnancy.

Funder

Focused Ultrasound Foundation Centre of Excellence

Isaac Newton Trust

Genesis Research Trust

Action Medical Research

British Heart Foundation

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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