Non‐invasive high‐intensity focused ultrasound treatment of the placenta: a preliminary in‐vivo study using a simian model

Abstract

This study demonstrates the feasibility of HIFU applied non-invasively to the placental unit in an in-vivo pregnant monkey model. The technique is safe in the immediate short term and is potentially translatable to human pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Noninvasive ablation of rabbit fetal and placental tissue targets in utero using magnetic resonance‐guided high‐intensity focused ultrasound

“…There was no effect on adjacent fetuses and when elbow or rib heating occurred, it was corrected for in subsequent sonications by increasing cooling time between sonications, stopping sonications prior to 20 seconds when they reach necrotic temperatures, verifying that test sonications were on target, and reducing movement using rocuronium bromide or excluding a potential HIFU tissue target because of excess movement. The lesions observed in the uterus were also seen in previous monkey studies . They did not span the width of the uterine wall nor were they verified on histologic examination as an irreversible change but simply as disruption in smooth muscle fiber patterns.…”

“…The high‐resolution MRI images provided sufficient resolution of small soft tissue targets to plan a HIFU beam path without acoustic‐field obstructions, including other fetuses or fetal boney structures (fetal limbs), aiming at targets that were smaller than those targeted using ultrasound guided studies . Ultrasound guided HIFU ablation in the monkey placenta and a second study in sheep used a hyper echoic area in posttreatment ultrasound images and confirmed as necrotic after postmortem histological examination . Posttreatment MRI images has a similar intrinsic change in grey scale after HIFU, corresponding to a change in vascular perfusion at the sonication point.…”

“…Our future studies include a 48‐hour time point to examine fully matured ablation zones. Protocols for placental HIFU as a noninvasive treatment for twin‐twin transfusion syndrome (TTTS) need to be established, as begun by Shaw et al and continued with others in the area of placental HIFU . As well as specific occlusion of vessels in larger organ models relevant for high perfusion congenital anomalies clinically in utero with HIFU …”

“…Treatments were either a single‐cell sonication or a line of sonications, attempting to cause necrosis in a larger area of tissue. Successful sonications achieved both temperature changes at necrotic levels as measured with MRI thermometry and in posttreatment scans as an intrinsic hyperintense area, similar to the hyperechoic area seen via ultrasound‐guided HIFU . The HIFU treatment sonication power applied to a target tissue was averaged over all treatment cells and presented as average acoustic power applied for the total cells +/− standard deviation.…”

“…There is limited preclinical research exploring the use of HIFU treatment in utero. Early studies indicate feasibility of HIFU delivery in utero using ultrasound imaging for guidance and confirmation of treatment effect with histology to confirm focal necrotic points . Placental HIFU ablation studies were able to achieve single‐spot necrosis in monkey, sheep, and rabbit placentas; as confirmed with a hyperechoic area in ultrasound imaging posttreatment, Doppler ultrasound flow changes, and then follow‐up histology .…”