Researchers have created a novel molecule imaging technique for seeing mRNA molecules in live mouse brains. The study offers a fresh understanding of how memories are created and retained in the brain and may one day help researchers better understand conditions like Alzheimer’s. The study was published in the Proceedings of the National Academy of Sciences (PNAS).

The method by which memory is really produced and stored in the brain is still shrouded in a great deal of uncertainty. It is generally known that the process of creating and storing memories causes the production of mRNA, a kind of RNA involved in the production of proteins, but the technology for investigating this process at the cellular level has been limited. In earlier research, the brains of mice were frequently dissected and examined.

The new molecule imaging technique provides scientists with a window into RNA creation in a mouse’s brain while the animal is still alive was created by a research team under the direction of a faculty member from the University of Minnesota Twin Cities.

“We still know very little about memories in the brain,” explained Hye Yoon Park, the study’s lead author and an associate professor in the University of Minnesota Department of Electrical and Computer Engineering. “It’s well known that mRNA synthesis is important for memory, but it was never possible to image this in a live brain. Our work is an important contribution to this field. We now have this new technology that neurobiologists can use for various different experiments and memory tests in the future.”

The procedure used by the team, which was directed by the University of Minnesota, included genetic engineering, two-photon excitation microscopy, and improved image processing software. The researchers were able to determine when and where the mouse’s brain released Arc mRNA by genetically altering the mouse to create mRNA that was tagged with green fluorescent proteins taken from a jellyfish.

The fact that the mouse is alive allowed the researchers to observe it for a longer amount of time. Using this novel molecule imaging technique, the researchers carried out two studies on the mouse in which they could observe in real time what the neurons, or nerve cells, were doing over the course of a month while the mouse developed and stored memories.

Neuroscientists have long hypothesized that certain neural networks fire in the brain during the formation of memories and then again during recall of those memories. But in both studies, the researchers discovered that separate neural networks activated on various days to activate the mouse’s memory.

In the retrosplenial cortex (RSC) region of the brain, they were able to identify a small cluster of cells that overlapped or consistently produced the Arc mRNA over the course of several days after the mouse formed this memory. They believe this cluster is in charge of the long-term storage of that memory.

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Wearable technology has become an essential component of our daily life, especially for chronic diseases such as diabetes and hypertension. Driven by advances in communications and computing and improved sensor accuracy, smartwatches have become real diagnostic tools capable of measuring vital signs while providing insights into our medical conditions. Efficiently measuring blood pressure with clinically proven accuracy has been a daunting task for smartwatch manufacturers. Many fitness trackers and smartwatches available on the market have developed such capability using the array of embedded sensors, however most of them did not get the Food and Drug Administration (FDA) approval. To this end, LiveMetric has recently announced receiving the FDA clearance for its watch-like wearable blood pressure monitoring solution, the LiveOne. The announced news is a potential bliss for chronic hypertension patients, notably as far as managing their conditions continuously with time.

The LiveOne Solution

Traditional medical grade blood pressure monitoring technology relies on cuffs that wrap around the arm. The cuff is then inflated manually or automatically until it fits tightly around the arm. Once it starts deflating, systolic and diastolic pressures are recorded giving the patient the two known readings used to estimate his condition.

The LiveOne wearable provides the same accuracy without the need for the bulky cuff, but also allowing continuous measurements that are taken every 10 seconds. According to the company’s press release, the pressure waveform out of the radial artery, the blood vessel that supplies blood to the hand, is recorded. The new design allows 24-hour ambulatory blood pressure measurements (ABPM) in addition to longer period blood pressure monitoring.

The blood pressure wearable relies on an array of nano-sensors built using microelectromechanical systems (MEMS) technology.  The output from these miniaturized sensing devices is processed by machine learning algorithms to determine the blood pressure values.

The results of a study involving the LiveOne device were published in article in the American Journal of Hypertension. The measurements collected from the device were compared to A-line measurements, that is, where blood pressure is measured through a radial artery intra-arterial catheter. Measurements using both techniques showed high correlation which indicates a notable accuracy in the readings of the wearable device.

A Promise to Hypertension Patients

The new device provides high hopes for individuals suffering from hypertension. Hypertension is a silent disease which means that not everyone having it, actually know they do. According to the world health organization (WHO), less than half of the adults with hypertension are diagnosed and treated. Besides its impact on the heart, brain, and kidneys, hypertension is one of the causes of premature death.

The possibility of having a wearable device that provides continuous blood pressure measurements is important towards discovering hypertension issues at the earliest. In the case of individuals with confirmed hypertension, the device allows a proper management of the medical condition including the efficiency of the administered medical treatment. In a nutshell, with the FDA-approval and the reported accuracy, the LiveOne device is a bliss for hypertension patients.

The Omron HeartGuide: An FDA-Approved Competitor

The LiveOne wearable blood pressure measuring device is not the only product with FDA-approval on the market. The Omron HeartGuide is another FDA-approved device that provides continuous blood pressure measurements. Omron tries to replicate oscillometry principles used in automatic cuff devices to a smartwatch. The key to this is the miniaturization of several components involved in traditional oscillometric measurements. The blood pressure measurements are recorded every 30 seconds compared to the 10 seconds of the LiveOne. However, the HeartGuide provides all the functionalities of a smartwatch including activity tracking, sleep monitoring and other additional features. The blood pressures measurements using the Omron requires the subject to raise the wrist to be at heart level, the embedded cuff will then inflate and the procedure continuous like traditional measurement techniques until the reading is displayed on the screen. When the LiveOne becomes commercially available,  the comparison with the Omron solution would be particularly interesting !

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The medical field has been benefiting a lot from technological advancements. The diagnostic, monitoring, and treatment tools have been getting smaller in size with ubiquitous usage capabilities and smarter decision-making. Ultrasound technology uses sound frequencies outside the human audible band, that is, above 20 kilohertz.  These safe waves are reflected from body structures, and processed by a computer to produce a picture of the intended organ or structure. Recently, portable ultrasound devices have emerged in the market allowing a practical usage of this popular technology.  As is the case with wireless electroencephalogram (EEG)  headsets or most recently earbuds, and other continuous measurements techniques that rely on sensors placed in contact with the body, numerous benefits can be achieved through an accurate and close follow-up of various medical conditions. The democratization of healthcare is another important side-effect as costly services can now be available to the public at affordable prices.

Can I Do My Ultrasound at Home?

 The advances of technology will soon allow solutions at home that do not require a specialist operating the machine. Think about it in a similar way to blood pressure measurement devices that can be worn on the wrist, or even diabetes management devices that are placed on the body surface or subcutaneously under the skin. The more plausible question is whether the measurements would be reliable and accurate. The aforementioned question is answered through technologies that allow the development of small electronic devices, such as transducers, that will faithfully capture data, similarly to large traditional machines and devices.  There has indeed been much progress in that direction. In 2019, a group of researchers in the university of British Columbia in Canada, have developed a portable ultrasound transducer, the size of a plaster, that can be woven into clothes or even integrated into small machines. The cost of the device has been estimated at a mere USD 100. The possibility of personal use depends on the advanced processing and analytics algorithms that can be applied. Processing of the data is needed to produce accurate representation of the organ or structure being investigated while advanced artificial intelligence are needed to interpret the collected data and give the individual a preliminary decision regarding his medical status. Finally, wireless connectivity is needed to connect the sensing devices to a smartphone to process and display the required information.

 Do Portable Ultrasound Systems Exist?

 Many unique devices are emerging in the market for a multitude of applications. A few years ago, General Electric has launched a portable ultrasound scanner, the Vscan. The device has been subsequently employed to tackle child mortality in Africa. Several other notable products are available on the market.

 Butterfly iQ+

Butterfly iQ+ is a portable ultrasound scanner device that can be directly connected to a smartphone or tablet through a proprietary Apple Lightning connection or USB type-C connection. The package comes with a myriad of services including various imaging possibilities, unlimited cloud storage, and a possibility for telemedicine services. The features of the device, which is priced at around USD 2400 have been tested for a large number of medical applications including anesthesiology, cardiology, emergency medicine, obstetrics, and many more. Additional analytics provide insights directly on the smart device.

 iiSono Health

iSono Health has recently obtained the Food and Drug Administration (FDA) approval for its wearable breast ultrasound imaging apparatus, named ATUSA. The system can be comfortably worn by the subject and images can be obtained in less than two minutes. Two- and three-dimensional images can further be analyzed through an AI-based software than can assist the physician with the decision-making process. This device is of notable importance for individuals genetically predisposed or having breast cancer as it allows screening at increased interval. This will further improve the control of the disease.

Coso

Male contraception is another application where ultrasound portable devices are used. Traditional approaches to contraception include male contraceptive pills, vasectomy, or the traditional condom usage. What Coso does is halting sperm regeneration through an ultrasound-based mechanism. The designed device is filled with water, which is then heated by the device to the required temperature. The subject’s testicles are then placed in water and subject to ultrasound waves which will induce the contraceptive effects which temporarily last for a couple of months, two weeks after the treatment is given. This indeed could be a solution that replaces hormonal-based pills or surgical-based vasectomies, providing a temporary contraceptive effect.

 Sustained Acoustic Medicine

Sustained acoustic medicine (SAM) is a therapeutic approach that uses low intensity long duration ultrasounds to heal soft tissues. This biomodulation technique has been used to treat chronic pain and other musculoskeletal injuries, notably for athletes. Many products have been released that use this ultrasound-based technology and some are already available on the market. Among other, companies such as Kinex and Zetroz have developed such projects using specially designed patches that could be placed on the injury location. Zetroz research and development  is supported by entities such as the US Department of Defense.

Summary

Ultrasound based treatments are no longer confined to hospitals and specialized centers. The advances in technology have paved the way for portable ultrasound devices, that can be used at a relatively low cost, everywhere. The addition of AI-based analytics and wireless connectivity further helps in monitoring medical conditions while assisting in the assessment process.

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