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dc.contributor.authorShaw, Caroline J
dc.contributor.authorRivens, Ian
dc.contributor.authorCivale, John
dc.contributor.authorBotting, Kimberley
dc.contributor.authorTer Haar, Gail
dc.contributor.authorGiussani, Dino
dc.contributor.authorLees, Christoph C
dc.date.accessioned2018-11-23T00:32:25Z
dc.date.available2018-11-23T00:32:25Z
dc.date.issued2018-09-11
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285818
dc.description.abstractPre-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.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectUterus
dc.subjectBlood Vessels
dc.subjectMiddle Cerebral Artery
dc.subjectUmbilical Arteries
dc.subjectFetus
dc.subjectPlacenta
dc.subjectAnimals
dc.subjectSheep
dc.subjectHumans
dc.subjectDisease Models, Animal
dc.subjectHemorrhage
dc.subjectUltrasonography, Prenatal
dc.subjectBlood Flow Velocity
dc.subjectPregnancy
dc.subjectFemale
dc.subjectHigh-Intensity Focused Ultrasound Ablation
dc.titleTrans-abdominal in vivo placental vessel occlusion using High Intensity Focused Ultrasound.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameSci Rep
prism.startingPage13631
prism.volume8
dc.identifier.doi10.17863/CAM.33162
dcterms.dateAccepted2018-06-28
rioxxterms.versionofrecord10.1038/s41598-018-31914-4
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-09-11
dc.contributor.orcidGiussani, Dino [0000-0002-1308-1204]
dc.contributor.orcidLees, Christoph C [0000-0002-2104-5561]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-09-11


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International