This Sticker Looks Inside the Body

2022-07-30
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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
对人体内部进行成像的超声波扫描仪是一种救命的医疗工具。现在,研究人员已经缩小了这种手持超声探头,这种探头通常需要一名训练有素的技术人员从皮肤上方向下移动到邮票大小的平面芯片上,并用一种特殊的生物粘合剂粘在皮肤上。这种新设备可以连续两天记录高分辨率视频,捕捉在运动中血管和心脏的活动,或在被试者吞咽果汁然后消化时胃的扩张和收缩。麻省理工学院(Massachusetts Institute of Technology)的机械工程师赵宣和(音译)说:“它的美妙之处在于,突然之间,你可以将这种超声探头、这种薄的超声扬声器粘附在身体上超过48小时。”赵宣和是一篇描述这种新设备的论文的合著者,该论文于周四发表在《科学》(Science)杂志上。通过在这段时间内记录内脏器官的静态图像和视频,可穿戴成像设备可以用于诊断心脏病发作和恶性肿瘤,测试药物的有效性,评估一般的心脏、肺或肌肉健康状况。“这可能会通过增强长期连续成像技术来改变医学成像的范式,”Zhao补充道,“它也可能会改变可穿戴设备领域的范式。”传统的超声波技术能够在不伤害身体的情况下观察皮肤下的情况,但这种扫描的途径有限。“传统的手持超声波需要训练有素的技术人员将探头正确地放在皮肤上,并在探头和皮肤之间涂上一些液体凝胶,”德克萨斯大学奥斯汀分校的机械工程师卢南树(音译)说。他没有参与这项新研究,但与人合著了《科学》杂志上的一篇分析报告。“你可以想象,这是非常乏味的,非常短期,非常有限的。”卢解释说,因为它们需要有经验的操作员,这些扫描是昂贵的,而且不能用于测试对象正在锻炼或让他们的身体承受高温或极端环境的压力。“传统的超声波检查有很多局限性,”她说。“如果我们能使超声波传感器可穿戴、可移动、可访问,这将打开许多新的可能性。”由于其潜在的多功能性,其他研究人员已经尝试制作粘贴在超声波贴片。但为了粘住柔软有弹性的皮肤,早期的设备本身就被设计成有弹性的。这种外形因素削弱了图像质量,因为它无法容纳那么多的传感器——在这种情况下,传感器是将电能转换成声波的,其频率太高,人耳无法探测到。超声波探头将这些波通过一层粘稠的凝胶送入人体,在那里它们被器官和其他内部结构反射,然后返回到换能器阵列。该系统将机械波转换回电信号,并将其发送到计算机上转换成图像。传感器越多,图像质量越好。“它与相机非常相似,”卢在德州大学奥斯汀分校实验室的电气工程师、研究生菲利普·谭(Philip Tan)解释道,他也没有参与这项新研究,但参与了分析文章的撰写。一种弹性的粘贴式超声波探头必须能够在皮肤每次移动时弯曲,它不能在阵列中装入太多的换能器——当佩戴者移动时,换能器的配置会发生变化,从而难以捕捉稳定的图像。 赵和他的团队没有让设备本身具有弹性,而是将一个只有三毫米厚的刚性探针连接到一层灵活的粘合剂上。这种粘合剂取代了传统超声棒和皮肤之间的粘稠液体,它是一种富含水的聚合物(水凝胶)和一种类似橡胶的材料(弹性体)的混合物。“它是一块固体水凝胶,含水量超过90%,但它像果冻一样处于固体状态,”赵说。“我们用这种非常薄的弹性体薄膜覆盖在果冻的表面,这样果冻内的水就不会蒸发掉。”这种生物粘合剂不仅能将探针牢牢地粘在皮肤上48小时,还能提供一层缓冲层,保护坚硬的电子设备不受皮肤和肌肉弯曲的影响。为了对不同的身体系统进行成像,赵的团队测试了能产生不同频率的波,从而穿透身体不同深度的探测器。例如,10兆赫兹这样的高频可能会传到皮肤下几厘米的地方。研究人员利用这一频率来捕捉受试者从坐着到站着或剧烈运动时血管和肌肉的活动。3兆赫的较低频率更深入,大约6厘米,以捕捉内部器官。利用这个频率,研究人员拍摄了一个受试者心脏的四个腔室的图像,并记录了另一个人的胃在他们的系统处理几杯果汁时排空的情况。赵说,研究人员还将用刚性超声探头采集到的图像与用可伸缩超声设备采集到的图像进行了比较。“你可以看到,我们的分辨率几乎比可拉伸超声波高出一个数量级(10倍),”他补充说。一种持续监控身体特定部位的成像设备可用于监测和诊断各种疾病。医生可以随着时间的推移密切关注肿瘤的生长。高血压高危人群可能会佩戴超声波贴片来测量他们的血压,在血压飙升时发出警报,或跟踪药物是否有帮助。COVID - 19患者可以呆在家里,知道如果他们的疾病导致肺部感染严重到需要住院治疗,成像设备会提醒他们。也许最重要的应用是检测和诊断心脏病发作。“心血管疾病是……在全世界,在美国也是如此。”其他可穿戴设备开发商也在关注心脏健康。例如,苹果手表等智能手表能够通过所谓的心电图(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——至少在某些情况下是这样。“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,大多数心脏病发作都需要成像手段来诊断,比如超声成像。”病人心脏的连续成像可以捕捉他们的症状并提供早期诊断。谭说:“这款新设备的最大卖点在于,它开启了在静态环境下无法完成的新型医疗诊断。”例如,要评估心脏健康状况,在运动时测量该器官的活动是有帮助的,但要拿着超声棒对着跑步的受试者粘在一起的胸部很难。谭补充说:“通过可穿戴超声波贴片,你不需要把换能器放在身上,他们实际上能够显示,即使在运动中,你也能够获得非常高质量的心脏图像。” 然而,这种生物粘附装置还没有准备好投入使用。首先,它还必须被物理连接到一台能够收集和分析探测器产生的数据的计算机上。“我们通过一根电线将这个探针连接到一个数据采集系统上,”赵说。“但我的团队正在努力将所有东西小型化,并集成到我们的无线设备中。”他最终计划用一个小型化的电源和一个无线数据传输系统来升级补丁。Lu和Tan认为,这是一个可行的目标,这要归功于缩小电子元件和制造方法,使这些特性能够组合成“芯片上的超声波”。卢建议,如果该领域能够吸引联邦和私人投资,这种设备将在五年内实现,尽管它仍需获得联邦监管机构的批准。最终,超声波贴纸可能会加入监测人类健康的可穿戴设备的行列,包括现有的收集心率、睡眠质量甚至压力信息的设备。“我们的身体辐射出很多关于我们的健康、情绪、注意力、准备等的高度个性化、高度连续、分布式和多模态数据。所以我们有大量的数据。”“问题是如何可靠地、持续地获得它们。”
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