This Sticker Looks Inside the Body

2022-07-30 14:43:32
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Ultrasound scanners, which image the inside of the human body, are a life-saving medical tool. Now researchers have shrunk the handheld ultrasound probe—which typically requires a highly trained technician to move over the skin—down to a flat chip that is the size of a postage stamp and sticks to the skin with a special bioadhesive. The new device can record high-resolution videos for two days at a stretch, capturing blood vessels and hearts laboring during exercise or stomachs expanding and shrinking as test subjects gulp juice and then digest it.

“The beauty of this is, suddenly, you can adhere this ultrasound probe, this thin ultrasound speaker, to the body over 48 hours,” says Xuanhe Zhao, a mechanical engineer at the Massachusetts Institute of Technology and co-author of a paper describing the new device, which was published in Science on Thursday. By recording still pictures and videos of internal organs during this time, a wearable imaging device could be used to diagnose heart attacks and malignant tumors, test the effectiveness of medications and assess general heart, lung or muscle health. “This can potentially change the paradigm of medical imaging by empowering long-term continuous imaging,” Zhao adds, “and it can change the paradigm of the field of wearable devices.”

Traditional ultrasounds are great at peering beneath the skin without causing damage to the body, but access to such scans is limited. “The conventional handheld ultrasound requires well-trained technicians to put the probe properly on the skin and apply some liquid gel between the probe and skin,” says Nanshu Lu, a mechanical engineer at the University of Texas at Austin, who was not involved in the new research but co-wrote an accompanying analysis in Science. “And as you can imagine, it’s quite tedious and very short-term, very constrained.” Because they require an experienced human operator, Lu explains, these scans are expensive, and they cannot be used in tests where the subject is exercising or putting their body under stress from heat or extreme environments. “Conventional ultrasounds have a lot of limitations,” she says. “If we can make ultrasound sensors wearable and mobile and accessible, it will open a lot of new possibilities.”

Thanks to their potential versatility, other researchers have attempted to make stick-on ultrasound patches. But in order to adhere to soft, stretchy skin, earlier devices were designed to be stretchable themselves. This form factor weakened image quality because it could not accommodate as many transducers—units that, in this case, transform electrical power into sound waves with frequencies too high for human ears to detect. An ultrasound probe sends these waves through a layer of gooey gel into the human body, where they bounce off organs and other internal structures and then return to the transducer array. This converts the mechanical waves back to electrical signals and sends them to a computer for translation into images.

The more transducers, the better the image quality. “It’s very similar to a camera,” explains Philip Tan, an electrical engineer and a graduate student at Lu’s lab at U.T. Austin, who was also not involved with the new study but co-wrote the analysis piece. A stretchy stick-on ultrasound probe, which must be able to flex every time the skin moves, cannot pack as many transducers into the array—and when the wearer moves, the configuration of transducers shifts and makes it difficult to capture stable images.

Instead of making the device itself stretchy, Zhao and his team attached a rigid probe, just three millimeters thick, to a flexible layer of adhesive. This adhesive replaces the gooey liquid placed between a traditional ultrasound wand and the skin, and it is a hybrid of a water-rich polymer called a hydrogel and a rubberlike material called an elastomer. “It is a piece of solid hydrogel containing over 90 percent water, but it is in a solid state like Jell-O,” Zhao says. “We cover the surface of this Jell-O with this very thin membrane of elastomer so that the water inside the Jell-O will not evaporate out.” This bioadhesive not only stuck the probe firmly to the skin for 48 hours, but it also provided a cushioning layer that protected the rigid electronics from the flexing of skin and muscles.

To image different body systems, Zhao’s team tested versions of the probe that produce waves at different frequencies and thus penetrate the body to different depths. For instance, a high frequency such as 10 megahertz might make it to a couple of centimeters beneath the skin. The researchers used this frequency to capture the action of blood vessels and muscles as test subjects shifted from sitting to standing or exercised vigorously. A lower frequency of three megahertz goes deeper, more like six centimeters, to capture internal organs. Using this frequency, the researchers imaged the four chambers of a subject’s heart, and recorded the stomach of another emptying out as their system processed a couple of cups of juice. The researchers also compared the images gathered with their rigid ultrasound probe with those captured by a stretchable ultrasound device, Zhao says. “You can see the resolution of ours is almost one order of magnitude [10 times] higher than the stretchable ultrasound,” he adds.

An imaging device that maintains a continuous watch over specific parts of the body could be used to monitor and diagnose a variety of ailments. Doctors could keep a close eye on the growth of a tumor over time. Someone at high risk of hypertension might wear an ultrasound patch to measure their high blood pressure, alerting them when the pressure spikes or tracking whether a medication is helping. A COVID patient could stay home, knowing that an imaging device would alert them if their illness caused a lung infection severe enough to require hospitalization. Perhaps the most important application could be in the detection and diagnosis of heart attacks. “Cardiovascular disease is ... the leading cause of death in the whole world, also in the U.S.,” Zhao says. Heart health is on the radar of other wearable device developers. For instance, smart watches such as the Apple Watch are capable of tracking the electrical signals that indicate heart activity with a so-called electrocardiogram (ECG or EKG). This can be used to diagnose heart attacks—at least in some cases. “There are already studies showing that EKG can only diagnose around 20 percent of heart attacks. The majority of heart attacks actually require imaging modalities, such as ultrasound imaging, to diagnose,” Zhao says. Continuous imaging of a patient’s heart could capture their symptoms and provide an early diagnosis.

“The big selling point of this new device is that it opens new types of medical diagnosis that can’t be done in a static setting,” Tan says. To assess heart health, for instance, it’s helpful to measure the organ’s activity while exercising—but it’s hard to hold an ultrasound wand against a running subject’s goo-covered chest. “With a wearable ultrasound patch, where you wouldn’t have to hold the transducer on the person, they were actually able to show that you’re able to get very high-quality images of the heart even during motion,” Tan adds.

The bioadhesive device is not ready for action yet, however. For one thing, it still has to be physically plugged into a computer that can collect and analyze the data the probe produces. “We connect this probe through a wire to a data acquisition system,” Zhao says. “But my group is working very hard to miniaturize and integrate everything into our wireless device.” He ultimately plans to upgrade the patch with a miniaturized power source and a wireless data-transmission system. This is a feasible goal, Lu and Tan agree, thanks to shrinking electronic components and fabrication methods that allow these features to be combined into an “ultrasound on a chip.” Lu suggests that if the field can attract federal and private investments, such a device could be feasible within five years, although it would still have to earn approval from federal regulators.

Ultimately, ultrasound stickers could join the ranks of wearables that monitor human health, including existing devices that gather information about heart rate, sleep quality and even stress. “Our human body is radiating a lot of a highly personal, highly continuous, distributed and multimodal data about our health, our emotion, our attention, our readiness, and so on. So we’re full of data,” Lu says. “The question is how to get them reliably and continuously.”

参考译文
这个贴纸看起来像身体内部
超声波扫描仪可以成像人体内部,是救命的医疗工具。现在研究人员将这种手持超声波探头——通常需要技术娴熟的专业人员在其皮肤上操作——缩小到一片邮票大小的平面芯片,并通过一种特殊的生物粘合剂附着在皮肤上。这个新设备可连续记录两天的高清视频,捕捉到测试对象在运动时血管和心脏的工作状态,以及他们在饮用果汁并消化时胃部的扩张与收缩。“这种装置的美妙之处在于,你突然就可以将这个超声波探头,这个超声波薄片扬声器,贴在身体上达48小时之久。”麻省理工学院的机械工程师赵宣和说道,他是描述这种新设备的研究论文的合著者,该论文周四发表在《科学》杂志上。通过在此期间记录内部器官的静态画面和视频,这种可穿戴的成像装置可用于诊断心脏病发作和恶性肿瘤、检测药物的效果,以及评估整体的心脏、肺部或肌肉健康状况。“这种装置有潜力通过实现长期连续成像而改变医学成像的范式,”赵宣和补充道,“它甚至可以改变可穿戴设备领域的范式。”传统超声波扫描仪在不损伤身体的情况下可以深入观察皮肤之下,但这种扫描的可及性非常有限。“传统的手持式超声波扫描仪需要经过良好训练的技术人员将探头正确放置在皮肤上,并在探头和皮肤之间涂抹一些液体凝胶,”德克萨斯大学奥斯汀分校的机械工程师陆南舒说道,她并未参与这项新研究,但与他人共同撰写了《科学》杂志上的分析文章。“你可以想象,这种操作非常繁琐,而且时间短暂,非常受限。”陆南舒解释说,因为这些扫描需要有经验的操作者,所以成本昂贵,而且不能用于受试者在运动或在高温或极端环境中承受身体压力的测试。“传统超声波扫描仪有很多限制,”她说,“如果我们能让超声波传感器变得可穿戴、可移动且易于获得,就会开启很多新的可能性。”由于其潜在的多功能性,其他研究人员也尝试开发可粘贴的超声波贴片。然而,为了附着在柔软、有弹性的皮肤上,早期设备设计成具有伸缩性。这种形状削弱了图像质量,因为它无法容纳足够的换能器——在本例中,这些换能器将电能转化为人耳无法听见的高频声波。超声波探头将这些声波通过一层粘稠凝胶发送进入人体,声波在器官和其它内部结构上反射后返回换能器阵列,再将其转化为电信号并发送至计算机生成图像。换能器越多,图像质量越好。“这非常类似于相机,”陆南舒实验室的电气工程师和研究生谭菲尔普说道,他也未参与这项新研究,但与他人共同撰写了该分析文章。可伸缩的贴片式超声波探头,每次皮肤移动都必须弯曲,因此无法在阵列中放入那么多换能器——当佩戴者移动时,换能器的排列会发生变化,使得稳定图像的捕捉变得困难。赵宣和的团队没有让装置本身具备伸缩性,而是将一个只有三毫米厚的刚性探头附着在一个柔软的粘合层上。这种粘合剂替代了传统超声波探头和皮肤之间使用的粘稠液体,它是一种由含水量高且富含水的聚合物(称为水凝胶)和类似橡胶的材料(称为弹性体)组合而成的混合物。“这是一种固体水凝胶,含水量超过90%,但它像果冻一样是固体的,”赵宣和说。“我们在果冻表面覆盖了一层非常薄的弹性膜,以防止果冻中的水分蒸发。”这种生物粘合剂不仅在48小时内将探头牢固地附着在皮肤上,还提供了一层缓冲,保护刚性的电子设备免受皮肤和肌肉的拉伸。为了成像不同的身体系统,赵宣和的团队测试了能够产生不同频率波的探头版本,从而穿透身体至不同的深度。例如,10兆赫的高频波可能仅能穿透到皮肤下几厘米处。研究人员用这种频率捕捉了测试对象从坐着到站立或剧烈运动时血管和肌肉的活动。3兆赫的低频波则可以深入大约6厘米,捕捉到内部器官。使用这种频率,研究人员成像了受试者心脏的四个腔室,并记录了另一个人在消化两杯果汁时胃部排空的过程。研究人员还比较了他们使用刚性超声波探头获得的图像与可伸缩超声波设备获得的图像,赵宣和说道。“你可以看到,我们的分辨率几乎是可伸缩超声波的十倍高,”他补充道。一种能够持续监控身体特定部位的成像装置可以用于监测和诊断各种疾病。医生可以持续关注肿瘤随时间的增长情况。高血压高风险人群可以佩戴超声波贴片测量血压,在血压飙升时及时提醒,或追踪药物是否有效。新冠患者可以在家中安心,知道若病情导致严重的肺部感染,需要住院治疗时,成像装置会及时提醒。也许最重要的应用是在心脏病发作的检测和诊断上。“心血管疾病是……全球和美国的主要死亡原因,”赵宣和说。其他可穿戴设备开发者也关注心脏健康。例如,苹果手表等智能手表可以通过所谓的心电图(ECG或EKG)跟踪显示心脏活动的电信号,这可以用于诊断心脏病发作——至少在某些情况下。“已经有研究表明,心电图只能诊断大约20%的心脏病发作。实际上,大多数心脏病发作需要成像方法,如超声波成像,才能进行诊断,”赵宣和说。对患者心脏进行连续成像可以捕捉到症状并提供早期诊断。“这种新设备最大的卖点在于,它可以开启无法在静态环境中完成的新类型医学诊断,”谭菲尔普说。例如,评估心脏健康时,在运动中测量器官的活动情况是有帮助的——但要在一个满是凝胶的人跑步时手持超声波探头是很难的。“有了可穿戴超声波贴片,不再需要手持换能器,他们实际上能够展示即使在运动过程中,也能够获得高质量的心脏图像,”谭菲尔普补充道。然而,这种生物粘合装置尚未准备好投入使用。一方面,它仍需连接到一台能收集和分析探头所产生数据的计算机。“我们通过一根电线将这个探头连接到数据采集系统,”赵宣和说。“但我所在的研究组正努力将所有东西小型化并集成到我们的无线设备中。”他最终计划升级贴片,增加一个微型电源和无线数据传输系统。陆南舒和谭菲尔普同意,这是一个可行的目标,得益于电子元件的小型化和制造方法的进步,这些功能可以集成到一种“芯片上的超声波”装置中。陆南舒表示,如果该领域能够吸引联邦和私人投资,这种设备可能在五年内变得可行,尽管它仍需获得联邦监管机构的批准。最终,超声波贴片可能加入监测人体健康的可穿戴设备行列,包括现有设备提供的信息如心率、睡眠质量,甚至压力等。“我们人体正在不断释放着关于我们健康、情绪、注意力和准备状态等高度个人化、持续、分布和多模态的数据。因此,我们充满了各种数据,”陆南舒说。“问题是如何可靠而持续地获取这些数据。”
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