Abstract
Pre-clinically, High Intensity Focused Ultrasound (HIFU) has been shown to safely and effectively occlude placental blood vessels in the acute setting, when applied through the uterus. However, further development of the technique to overcome the technical challenges of targeting and occluding blood vessels through intact skin remains essential to translation into human studies. So too does the assessment of fetal wellbeing following this procedure, and demonstration of the persistence of vascular occlusion. At 115 ± 10 d gestational age (term~147 days) 12 pregnant sheep were exposed to HIFU (n = 6), or to a sham (n = 6) therapy through intact abdominal skin (1.66 MHz, 5 s duration, in situ ISPTA 1.3–4.4 kW.cm−2). Treatment success was defined as undetectable colour Doppler signal in the target placental vessel following HIFU exposures. Pregnancies were monitored for 21 days using diagnostic ultrasound from one day before HIFU exposure until term, when post-mortem examination was performed. Placental vessels were examined histologically for evidence of persistent vascular occlusion. HIFU occluded 31/34 (91%) of placental vessels targeted, with persistent vascular occlusion evident on histological examination 20 days after treatment. The mean diameter of occluded vessels was 1.4 mm (range 0.3–3.3 mm). All pregnancies survived until post mortem without evidence of significant maternal or fetal iatrogenic harm, preterm labour, maternal or fetal haemorrhage or infection. Three of six ewes exposed to HIFU experienced abdominal skin burns, which healed without intervention within 21 days. Mean fetal weight, fetal growth velocity and other measures of fetal biometry were not affected by exposure to HIFU. Fetal Doppler studies indicated a transient increase in the umbilical artery pulsatility index (PI) and a decrease in middle cerebral artery PI as a result of general anaesthesia, which was not different between sham and treatment groups. We report the first successful application of fully non-invasive HIFU for occlusion of placental blood flow in a pregnant sheep model, with a low risk of significant complications. This proof of concept study demonstrates the potential of this technique for clinical translation.
Highlights
High Intensity Focused Ultrasound (HIFU) is an established non-invasive therapeutic technique with applications in in oncology and neurosurgery
Consistently occlude placental vessels in a pregnant sheep model using a transuterine approach via laparotomy. This demonstrated short term placental vascular occlusion and fetal survival following the application of HIFU; cardiovascular and metabolic invasive assessment of fetal responses suggested that the technique was safe in the acute setting[3]
In 2 of the 5 HIFU exposure series which resulted in failed occlusion, problems with control of movement of the mechanised gantry arm resulted in HIFU not being delivered as planned, a situation which had previously resulted in vessel haemorrhage
Summary
High Intensity Focused Ultrasound (HIFU) is an established non-invasive therapeutic technique with applications in in oncology and neurosurgery. Consistently occlude placental vessels in a pregnant sheep model using a transuterine approach via laparotomy This demonstrated short term (up to 4 hours) placental vascular occlusion and fetal survival following the application of HIFU; cardiovascular and metabolic invasive assessment of fetal responses suggested that the technique was safe in the acute setting[3]. It remains important to demonstrate that a HIFU treatment protocol can safely deliver sufficient energy into the intrauterine space to achieve successful vascular occlusion with transducers placed external to the skin, not just the uterus, to justify its description as a non-invasive technique. In this next-stage study, the objective was to further develop the techniques used previously. We describe maternal and fetal recovery from HIFU placental vascular occlusion and describe side-effects
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