MICA: A Non-invasive Ultrasound-guided High Intensity Focused Ultrasound system for placental and fetal vascular ablation

双胞胎输血综合征(TTTS)影响10%-15%的同卵双胞胎共享胎盘。在英国，这可能需要对每年约400-600名婴儿进行高风险的治疗。在TTTS中，血液通过胎盘中被称为吻合口的异常血管连接从一个双胞胎转移到另一个，这些血管直接连接双胞胎的血液供应。这些吻合术可能会导致双胞胎中的一人血液和羊水减少，而另一人的血液和羊水过多。TTTS是导致同卵双胞胎早产、死亡或残疾的最大原因。TTTS可以通过专业的超声波扫描进行检查。患有严重TTTS的女性结局最差，建议进行一种治疗，通过阻断导致TTTS的异常血管连接来分割双胞胎的胎盘。目前，这是使用一种名为胎儿镜激光的技术完成的，这是一种外科手术，将2-4毫米宽的器械放入子宫，这样它就可以到达胎盘。由于激光必须放在子宫内，这种治疗方法有风险，可能会导致流产、子宫出血或感染，或者子宫液体泄漏，这可能会影响双胞胎的发育。这就是为什么胎儿镜下激光只用于严重的病例；风险太高，不能用于不那么严重的病例。在英国，每年约有100-150名妇女在18周前被诊断为严重的TTTS。即使他们需要治疗，也不能使用胎儿激光，因为风险太高，仪器太大。这是一群妇女，她们的孩子在所有被诊断为TTTS的人中结局最差，但我们没有好的、安全的治疗方法。我们的研究小组使用高强度聚焦超声(HIFU)，它使用非常强大的超声波，可以阻塞胎盘中的血管，而不需要在子宫上钻一个洞。由于HIFU不需要进行侵入性手术，我们可以用它来治疗妊娠18周以下的重度TTTS。到目前为止，我们已经在怀孕的绵羊身上测试了这种治疗方法，这与人类怀孕有相似之处。根据这些实验，HIFU似乎效果良好，是一种安全的阻断胎盘血管的方法。在伦敦夏洛特女王和切尔西医院，我们将与来自伦敦癌症研究所的HIFU专家、国际胎儿医学专家、妊娠支持组织和具有TTTS经验的患者志愿者一起设计一项临床研究。作为一项精心设计的研究的一部分，我们将为大约13名在18周前被诊断为TTTS的妇女和婴儿提供HIFU治疗。在这项非常早期的研究中，主要观察这项技术对母亲和婴儿是否安全，以及我们是否能阻止血液通过连接胎盘两半的异常血管流动。如果HIFU是安全有效的，它将避免在怀孕18周时进行风险更高的激光治疗，并很可能导致进一步的更大规模的临床试验。作为这项研究的一部分，我们将建立一个特殊的超声引导HIFU系统，它结合了可用的最佳婴儿和胎盘血管超声成像和专门设计的HIFU系统，将治疗准确地引导到胎盘中正确的区域。我们还将设计一个特殊的计算机程序来控制整个系统。在不伤害母亲或婴儿的情况下修复异常的胎盘血管是困难的。我们在绵羊身上做的实验已经向我们展示了可能发生的一些问题。没有地方可以买到HIFU系统，它可以拍出足够好的图像，或者允许准确地治疗异常血管。因此，我们需要构建一个用于此研究的模型。我们建立的HIFU系统在未来也可能用于治疗怀孕期间可能发生的其他问题或癌症治疗，在这些问题上，它可能会阻塞供肿瘤生长的血管。

Twin-Twin Transfusion Syndrome (TTTS) affects 10-15% of identical twins who share a placenta. This may need treatment that is high risk for around 400-600 babies every year in the UK. In TTTS, blood moves from one twin to the other through abnormal blood vessel connections in the placenta called anastomoses, which directly link the blood supplies of the twins. These anastomoses may cause one twin to get less blood and amniotic fluid and the other twin too much blood and amniotic fluid. TTTS is the biggest cause of premature birth, death or disability in identical twin pregnancies.TTTS can be seen with a specialist ultrasound scan. Women who have severe TTTS have the worst outcomes, and are recommended to have a treatment which can divide the twins' placenta by blocking the abnormal blood vessel connections that cause TTTS. At the moment this is done using a technique called fetoscopic laser, a surgical procedure where a 2-4 mm wide instrument is placed into the womb so it can reach the placenta. As the laser must be put inside the womb, this treatment is risky and can cause miscarriage, bleeding or infection in the womb, or leakage of fluid from the womb which can affect the twins' development. This is why fetoscopic laser is only used in serious cases; the risks are too high to for it to be used in cases that are not as serious.In the UK about 100-150 women per year have severe TTTS diagnosed before 18 weeks. Even though they need treatment, fetoscopic laser cannot be used because the risks are too high and instruments too big. This is a group of women whose babies have the worst outcomes of all those diagnosed with TTTS, but we have no good, safe treatments for them. Our research group works with High Intensity Focused Ultrasound (HIFU), which uses very powerful ultrasound waves that can block blood vessels in the placenta without needing to make a hole in the womb. As HIFU does not require invasive surgery to be done, we could use it to treat severe TTTS in pregnancies below 18 weeks. So far, we have tested this treatment in pregnant sheep, which share similarities to human pregnancies. Based on these experiments HIFU seems to be work well and is a safe way to block placental blood vessels.At Queen Charlotte's and Chelsea Hospital, London, we will work with experts in HIFU from the Institute of Cancer Research, London, international fetal medicine experts, pregnancy support groups and patient volunteers with experience of TTTS to design a clinical study. We will offer around 13 women and babies diagnosed with TTTS before 18 weeks the HIFU treatment as part of a carefully designed study. In this very early stage study look primarily at whether the technique is safe for mothers and babies and if we can stop blood flowing through the abnormal vessels connecting the two halves of the placenta. If HIFU is safe and effective, it would prevent the need for riskier laser treatment when these pregnancies reach 18 weeks and will most likely lead on to further, larger clinical trials.As part of this study, we will build a special ultrasound guided HIFU system that combines the best available ultrasound imaging of the babies and placental blood vessels with a HIFU system specially designed to direct the treatment to exactly the right area in the placenta. We will also design a special computer program to control the whole system. Fixing the abnormal placental blood vessels without harming the mother or the babies is difficult. The experiments we have done in sheep has shown us some of the problems that might happen. There are no places to buy a HIFU system that makes good enough pictures or allows accurate treatment of the abnormal blood vessels. Therefore we need to build a one to use in this study. The HIFU system we build may also be used in the future for treating other problems that can happen in pregnancy or for cancer treatment, where it could block the blood vessels that feed tumours.