Can Ultrasound be Used to Improve Prosthetic Device Function?

Ultrasound technology has continued to be miniaturized at a rapid pace for the past several decades. Recently, handheld smartphone-sized ultrasound systems have emerged and are enabling point-of-care imaging in austere environments and resource-poor settings. With further miniaturization, one can imagine that wearable smartwatch-sized imaging systems may soon be possible. What new opportunities can you imagine with wearable imaging? My research group has been pondering this question for a while, and we have been working on an unexpected application: using ultrasound imaging to sense muscle activity and volitionally control robotic devices.Bebionic

Since antiquity, humans have been working on developing articulated prosthetic devices to replace limbs lost to injury. One of the earliest designs of an articulated mechanical prosthetic hand dates from the Second Punic War (218–201 BC). However, robust and intuitive volitional control of prosthetic hands has been a long-standing challenge that has yet to be adequately solved. Even though significant research investments have led to the development of sophisticated mechatronic hands with multiple degrees of freedom, a large proportion of amputees eventually abandon these devices, often citing limited functionality as a major factor.

A major barrier to improving functionality has been the challenge of inferring the intent of the amputee user and to derive appropriate control signals. Inferring the user’s intent has primarily been limited to noninvasively sensing electrical activity of muscles in the residual limbs or more invasive sensing of electrical activity in the brain. Commercial myoelectric prosthetic hands utilize 2 skin-surface electrodes to record electrical activity from the flexor and extensor muscles of the residual stump. To select between multiple grips with just these 2 degrees of freedom, users often have to perform a sequence of non-intuitive maneuvers to select among pre-programmed grips from a menu. This rather unnatural control mechanism significantly limits the potential functionality of these devices for activities of daily living.

Recently, systems with multiple electrodes that utilize pattern recognition algorithms to classify the intended grasp end-state from recorded signals have shown promise. However, the ability of amputees to translate end-state classification to intuitive real-time control with multiple degrees of freedom continues to be limited.

To address these limitations, invasive strategies, such as implanted myoelectric sensors are being pursued. Another approach, known as targeted muscle reinnervation, involves surgically transferring the residual peripheral nerves from the amputated limb to different intact muscle targets that can function as a biological amplifier of the motor nerve signal.  While these invasive strategies have exciting promise, there continues to be a need for better noninvasive sensing.

Recently, our research group has demonstrated that ultrasound imaging can be used to resolve the activity of the various muscle compartments in the residual forearm. When amputees imagine volitionally controlling their phantom limb, the innervated residual muscles in the stump contract, and this mechanical contraction can be visualized clearly on ultrasound. Indeed, one of the major strengths of ultrasound is the exquisite ability to quantify even minute tissue motion. Contractions of both superficial and deep-seated functional muscle compartments can be spatially resolved enabling high specificity in differentiating between different intended movements.

Our research has shown that sonomyography can exceed the grasp classification accuracy of state-of-the-art pattern recognition, and crucially enables intuitive proportional position control by utilizing mechanical deformation of muscles as the control signal. In studies with transradial amputees, we have demonstrated the ability to generate robust control signals and intuitive position-based proportional control across multiple degrees of freedom with very little training, typically just a few minutes.

We are now working on miniaturizing this technology to a low-power wearable system with compact electronics that can be incorporated into a prosthetic socket and developing prototype systems that can be tested in clinical trials. The feedback we have received so far from our amputee subjects and clinicians indicates that this ultrasound technology can overcome many of the current challenges in the field, and potentially improve functionality and quality of life of amputee users.

Now, if only noninvasive ultrasound neuromodulation can be used to provide haptic and sensory feedback to amputee users in a closed loop ultrasound-based sensing and stimulation system, we will be a step closer to restoring sensorimotor functionality to amputee users, and a grand challenge in the field of neuroprosthetics may be within reach. That will, of course, require some more research.

I was attracted to ultrasound research as a graduate student because of the nearly limitless possibilities of ultrasound technology beyond traditional imaging applications. As wearable sensors revolutionize healthcare, perhaps wearable ultrasound may have a role to play. One can only imagine what other novel applications may be enabled as the technology continues to be miniaturized. I think it is an exciting time to be an ultrasound researcher.

 

What new opportunities can you imagine with wearable imaging? Are you working on something using miniaturized ultrasound? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Siddhartha Sikdar, PhD, is a Professor in the Bioengineering Department in the Volgenau School of Engineering at George Mason University.

The Future of Point-of-Care Ultrasound in Pediatric Emergency Medicine

Pediatrics entices practitioners with its focus on treating illness in the youngest patients, for long-term outcomes of future growth and development. When I reflect on my own journey through Pediatrics and Pediatric Emergency Medicine, helping patients in real-time through providing the best quality care given limited information, drew me to Pediatric Emergency Medicine.

Lianne Profile FinalPediatric Emergency Medicine (PEM) focuses on providing acute care to patients from the newest newborns to teenagers. With this breadth of ages comes differing pathology, physiology, and of course differences in relative and absolute size. Integration of point-of-care ultrasound (POCUS) into PEM practice offers the clinician an added tool to provide the best possible care. Children are ideal patients for POCUS scanning as they often have slimmer body habitus, fewer comorbidities, and there is increasing interest in limiting ionizing radiation amongst all patients, especially the very young.

POCUS offers direct visualization for procedures such as endotracheal tube airway confirmation, central-line insertion, and intravenous and intraosseous access. Utilizing this clinical adjunct allows for accuracy in nerve block administration, reducing the volume used of local anesthetic and decreasing the need for systemic sedation. Visualizing fractures following reduction and assessing joints and soft tissue infections prior to decision of incision and drainage or aspiration can all be achieved using POCUS.

Because our patients vary in size, optimizing planning prior to starting procedures can help to maximize success. Risk in pediatric procedures are heightened due to variable sizing, risking too-deep insertion of needles and endotracheal tubes. Direct visualization helps to support the provider in making safe choices.

Beyond procedures, POCUS allows PEM providers to optimize resuscitation, through real-time monitoring of volume status, cardiac function, and pulmonary edema. Reassessment throughout resuscitation adds additional information to vital signs and end-organ markers as patients are treated.

As machines become increasingly accurate at more portable sizes, and as cloud storage is increasingly popular among organizations, the future of POCUS offers providers along the care-continuum the opportunity to share information and images. My hope for the future of acute POCUS would be to have pre-hospital POCUS, emergency POCUS, consultative radiology imaging, and follow-up POCUS imaging in community clinics on an integrated system allowing for shared images and progressive monitoring for long-standing conditions.

The future of POCUS is bright as innovation and technology disruption move ultrasound outside of the walls of the hospital, placing transducers in the hands of those at the bedside from the helicopter to the remote health clinic. For countries such as Canada, increased portability means increasing access for those populations most at risk of health inequity, those living in the far North and remote regions of my country, who have limited access to urban care. POCUS with added portability and technological integration can help improve access, and shared decision making between urban centers and remote regions with patient safety and privacy as a priority.

I’m excited to see where POCUS integration moves in the course of the rest of my medical career, as I look forward to being an advocate for access and clinical education in addition to being an expert that maintains clinical accountability, safety, and privacy. The promotion of these critical pillars will help determine the success of the POCUS-empowered clinical experience.

 

Do you use point-of-care ultrasound in pediatric practice? If so, how has it helped you? Is there another medical field you think should use ultrasound more? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Lianne McLean, MB BCh, BAO, FRCPC, is Assistant Professor at the University of Toronto; and Staff Physician and Chair of the Council of Informatics & Technology in the Division of Emergency Medicine at the Hospital for Sick Children in Toronto, Canada.

SonoBowl: A Game, A Challenge, An Education

SonoBowlOn July 12, 2018, 4 teams of 4 sonography students each competed in the inaugural SonoBowl, a game pitting the students’ ultrasound knowledge and skills against each other. Howard Community College (HCC) hosted the event, which the American Institute of Ultrasound in Medicine (AIUM) sponsored, and teams from Howard Community College; Montgomery College; Pennsylvania College of Health Sciences; and University of Maryland, Baltimore County participated. Although only 4 students from each team could participate, many more attended to observe.

IMG_0534

SonoBowl teams: HCC Sound Dragons are in red (as is their dragon), UMBC Dopplergangers are in black, PA Penguins are in white (4 in front), and MC Ultrasonic are in white (middle and back rows). AIUM staff are in blue.

If you are interested in hosting your own SonoBowl, you’re in luck. AIUM will be sharing instructions on recreating it, enabling schools around the country and abroad to create their own SonoBowl, where sonography students can come together to compete in ultrasound with question-and-answer sessions, scanning, and case challenges. The following is a review of the inaugural  SonoBowl. If you want all of the details, you’ll need a copy of the SonoBowl Playbook. If you are interested in receiving a copy of the SonoBowl Playbook, please let us know.

HCC and AIUM worked together to quickly pull this event together in just 2 months, including 6 conference calls and meetings—planning the itinerary, developing questions and case challenges, inviting teams and registering them, and setting up the event. Development began in May and concluded with the event, which included:

  • Round 1, Who Gives a Kahoot?: 30 multiple-choice questions and 1 bonus multiple-choice question on Kahoots;20180712_094549
  • Round 2, Mission I’m Possible: 3 rounds of scanning testing vascular, obstetric, and abdominal knowledge; and
  • Round 3, Have You Hertz About My Case Study?: A case challenge.

Round 1 was a question-and-answer session. Each team was supplied (by HCC) with a tablet to use for answering the questions as quickly as they could, as wins were based on speed as well as accuracy. The questions were developed by AIUM with input from Directors and faculty from the schools.

IMG_0591Round 2, which can be seen in this video, was a hands-on demonstration of the students’ skills. The teams were given 15 minutes at each station, equipped with an ultrasound machine and a model, to complete their task and answer the questions, which were provided on a form in an envelope and could be completed on a provided clipboard. A proctor at each station reviewed the image obtained for the task and indicated on the form whether it was correct and whether the answers to the question were each correct. After 15 minutes, the teams would rotate stations until all teams had competed at each station.

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For those students who attended but were not participating, a scavenger hunt was developed to fill this time. The students were randomly divided into 4 teams, each of which included students from each of the schools. Each team was given a campus map and a list hinting at 15 things to find around the campus. They were tasked with answering questions for some and taking a selfie at each to prove they found them. For example, one such hint was “Orange is definitely your color! Take a selfie with your face in the circle,” referring to a sculpture outside one of the buildings. Once Round 2 was complete, a lunch was provided.

Round 3 began with an announcement of where each team stood in the competition; HCC DMS Sound Dragons were in 4th place with 58 points, MC Ultrasonic was in 3rd with 66 points, and
UMBC Dopplergangers and PA Penguins were tied with 74 points each. Knowing how many points they had and the topic of the case study (gynecologic ultrasound), each team then indicated how many points they were willing to wager for the final round. All teams wagered their full points balance.

The teams were given a brief history for a case and shown the ultrasound images associated with it, then were given 1 minute to indicate which of 4 diagnoses was the correct one. After time was up, each team was asked to show their wager, beginning with the last place team, and the scores were adjusted based on their wager and whether they answered correctly. For this inaugural SonoBowl, MC Ultrasonic won the day with 132 points and was awarded the trophy to hold onto until next year’s SonoBowl, when it will be back up for grabs. Each of the winning team’s members also won a free AIUM student membership for a year and an insulated lunch bag containing AIUM gifts.

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If you are interested in receiving a copy of the SonoBowl Playbook, please let us know.

The American Institute of Ultrasound in Medicine is a multidisciplinary medical association of more than 9000 physicians, sonographers, scientists, students, and other health care providers. Established in the early 1950s, the AIUM is dedicated to advancing the safe and effective use of ultrasound in medicine through professional and public education, research, development of guidelines, and accreditation.

Ultrasound in Orthopedic Practice

Point-of-care ultrasound brings great value to patient care in orthopedic practice, especially for soft tissue problems. It offers safe, cost effective, and real-time evaluation for soft tissue pathologies and helps narrow down the differential diagnosis.Pic1

There are variety of soft tissue lesions in orthopedic practice with classic clinical presentation that may not necessitate ultrasound examination for confirmation of diagnosis, for example ganglion cyst. However, there is value in performing an ultrasound scan for these common soft tissue lesions.

Ganglion cyst on the dorsum of the wrist or radial-volar aspect of the wrist are confirmed based on clinical examination and presentation. Adding ultrasound examination can help differentiate classic ganglion cyst from some rare findings like Lipoma, anomalous muscles, or soft tissue tumors. Ultrasound examination may also be helpful in finding the source of the ganglion cyst or the stalk of the ganglion cyst. This can help pre-surgical planning if resection of the ganglion cyst is desired by the patient and recommended by the surgeon, because arthroscopic or traditional surgical approach may be needed based on the location of the stalk or neck of the cyst.

Images 1 and 2 show examples of two different patients with similar presentation of slow growing mass on the digit. Image 1 from patient 1 shows a solid tumor overlying the flexor tendons of the digit, where the mass was palpated. Image 2 from patient 2, shows a cystic mass overlying the tendons of the digit. In both of the cases, masses were painless and slow growing with minimal to no discomfort. Ultrasound is a great tool in differentiating solid vs cystic lesions and can help avoid attempted aspiration of a solid mass when the mass is presented in an area of classic ganglion cyst’s usual presentation.

Another soft tissue problem, where ultrasound is a superior imaging tool is tendon pathology. Ultrasound can help differentiate tendinosis, tenosynovitis, or tendon tears.

In tenosynovitis, tendon by itself shows normal echotexture and uniform appearance but the tenosynovium that surrounds the tendon gets inflamed and appears as hypoechoic halo around the tendon, for example, in image 3, tendons of the first dorsal compartment of the wrist show uniform thickness and fibrillar echotexture, however there is hypoechoic swelling around the tendons, this is an example of tenosynovitis of first dorsal compartment of the wrist.

In tendinosis, tendon loses its fibrillar pattern and appears swollen and may show vascularity on color ultrasound, which is suggestive of neoangiogenesis or angiofibroblastic proliferation. For example, in Image 4, the tendons of the first dorsal compartment of the wrist show focal enlargement, hypoechoic swelling, and loss of normal fibrillar echotexture and tendon appears disorganized with evidence of increased vascularity on color ultrasound. This is an example of tendinopathy or tendinosis.

Focal tendon tears appear as anechoic or hypoechoic focal defects in tendon substance. Image 5 shows partial tear of the triceps tendon from the olecranon process. The partial tear appears as a focal hypoechoic defect in the tendon, which is confirmed in the long and short axis scan of the tendon.

In full thickness tears, the tendon is seen retracted proximally with no fiber attachment at the tendon foot print. Image 6 shows example of a full thickness complete tear of the supraspinatus tendon from its bony attachment at the greater tubercle. The tendon has retracted proximally and the retracted stump is not visible on ultrasound examination.

Image 6

Point-of-care ultrasound adds significant value to clinical examination in orthopedic setting. It enhances the understanding of a patient’s problem, increases confidence in care provided, and high patient satisfaction is reported.

 

In what unexpected ways do you find ultrasound to be useful? Do you have additional tips for using ultrasound in orthopedics?  Comment below or let us know on Twitter: @AIUM_Ultrasound.

Mohini Rawat, DPT, MS, ECS, OCS, RMSK, is program director of Fellowship in Musculoskeletal Ultrasonography at Hands On Diagnostics and owner of Acumen Diagnostics. She is ABPTS Board-Certified in Clinical Electrophysiology; ABPTS Board-Certified in Orthopedics; registered in Musculoskeletal Sonography, APCA; and has an added Point-of-Care MSK Soft Tissue Clinical Certificate.

Training Beyond Discipline – Developing Devotion in Ultrasound

Mathews Benji KA point-of-care ultrasound (POCUS) revolution is unfolding before our eyes, forever changing the way we interact with patients. It started with a revolution in specialties such as emergency medicine and critical care, and now it has entered into my sphere with internal medicine and hospital medicine. I see this whenever I’m on clinical service. A 3rd year medical student talks about diffuse B-lines as we stop antibiotics and start diuretics on a patient with pulmonary edema; a 3rd year resident asks to look at a patient’s kidney with ultrasound as we manage undifferentiated acute kidney injury; nursing staff curiously looking on as a patient is shown their weak heart as goals of care are discussed.

At the same time, we in internal medicine and hospital medicine are living in a medical world filled with many challenges towards implementation of POCUS. Though there are many devices in the emergency rooms and some in the critical care wards, there are not many in the inpatient wards nor in the clinics. Though numerous workshops and courses abound in POCUS, many attendees do not continue to use this skillset after training. Those that received initial training find it too challenging to discipline themselves to continue to scan.

It is that latter sentiment that caught my attention this last year. The concept of discipline and viewing POCUS through its lens. A quote by Luciano Pavarotti comes to mind,

“People think I’m disciplined. It is not discipline. It is devotion. There is a great difference.”

I’ve often heard the sentiments:

“It is so hard to learn POCUS, how do you find the time for it on a busy clinical service to get images?”

“I find it hard to set aside time during my non-clinical work days as other work and life piles up.”

I’m not sure about you, but the word discipline does not often carry an inspirational tone to it. There is a sense of drudgery, lack of passion surrounding the word. As an ultrasound director, that is the farthest from what I want my learners to experience with POCUS.

When I looked up the word discipline in the Oxford Dictionary there it was as well:

dis·ci·pline
noun
1.
the practice of training people to obey rules or a code of behavior, using punishment to correct disobedience.
“a lack of proper parental and school discipline”

2.
a branch of knowledge, typically one studied in higher education.
“sociology is a fairly new discipline”

Is it #1 that we were aiming for? Or at the very least, is that what people are sensing? Hopefully, we’re not using punishment to correct disobedience. The Pavorotti quote struck a chord in me. As a contrast to discipline, we have devotion.

The word “devotion” is defined by Oxford Dictionary as follows:

de·vo·tion
noun
1.  love, loyalty, or enthusiasm for a person, activity, or cause.
“Eleanor’s devotion to her husband”
synonyms: loyalty, faithfulness, fidelity, constancy, commitment, adherence, allegiance, dedication; More

•  religious worship or observance.
“the order’s aim was to live a life of devotion”
synonyms: devoutness, piety, religiousness, spirituality, godliness, holiness, sanctity
“a life of devotion”

•  prayers or religious observances.
plural noun: devotions
synonyms: religious worship, worship, religious observance

Devotion does have some concepts borne from religion or worship but that doesn’t make it an irrelevant word for the POCUS learner or teacher. The first definition of love, loyalty, or enthusiasm captures the essence of what most of us are hoping POCUS to be for our learners. As my good friend and POCUS enthusiast, Dr. Gordy Johnson, from Portland, Oregon, says, we need to remember “our first kiss.” What was the moment that grasped us with POCUS?

Don’t get me wrong, I’m not completely opposed to the word discipline, but it moves beyond that if we’re going to develop fully devoted clinicians in the realm of bedside ultrasound. Those that are equipped with the cognitive elements know when POCUS should be used, why it should be used, how to acquire images, and then how to clinically integrate it.

This post was originally intended as a follow-up of the AIUM webinar on the Comprehensive Hospitalist Assessment & Mentorship with Portfolios (CHAMP) Ultrasound Program with hopes to continue the conversation surrounding what makes for an effective training program. The program involved online modules, an in-person course with assessments, portfolio development, refresher training, and final assessments. The key lesson we have learned is that longitudinal training with deliberate practice of POCUS skills with individualized performance feedback is critical for skill acquisition. However, the intangible pieces of how people continued to scan was developing an enthusiasm and love surrounding ultrasound by seeing its impact in the marketplace. As they were continuing to scan, their patients, their students, the many nursing staff were partnering in a stronger way with this diagnostic powerhouse in their hands.

With all this, I cannot help but be optimistic when I see the commitment of many in the POCUS movement already. I would urge all of us to evaluate how we develop devotion in ultrasound, how to tap into the dynamism of the POCUS movement coming up the pipeline with our medical students and residents. They have the potential to disrupt inertia and be an impactful force to integrate POCUS more into internal medicine and hospital medicine.

 

If you are an ultrasound educator, how do you inspire devotion? What are some of your best practices surrounding training in POCUS? Which do you think is most important: discipline or devotion? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Benji K. Mathews, MD, FACP, SFHM, is the Ultrasound Director of the Department of Hospital Medicine at HealthPartners in St. Paul, Minnesota.

Pre-eclampsia, Growth Restriction, and a Placenta Bank

Our Maternal-Fetal Medicine fellow was talking about a delivery that occurred while I was away. The fetus was growth-restricted and developed worsening indices on Doppler ultrasound of the umbilical arteries. What was initially an increased Systolic/Diastolic ratio became first absent and then reversed end-diastolic flow. As this occurred over several weeks, the patient herself had worsening blood pressures and symptoms related to her pre-eclampsia and the fetal tracing became more concerning. She was ultimately delivered and her tiny and premature baby was now in the care of the neonatologists.201500581_Hill-7

The fellow’s presentation focused on the ultrasound findings and the surveillance of pregnancies that become complicated in this way. What was known was the best current management in this case. The unknown was why this had happened in the first place. I was about to interrupt the presentation when our fellow, knowing what I was going to ask, looked over at me and said “Yes, I did collect the placenta.”

Pre-eclampsia is a common condition and growth restriction, by definition, occurs in 10% of pregnancies. The conditions are highly related. We have risk factors for both, but we seldom know the cause. Our treatments seem crude to a bench researcher; try to control the condition as long as you can, and if either patient or her fetus becomes too sick, deliver the pregnancy.

As an obstetrics and gynecology resident I was fascinated by developmental programming in these fetuses and sent in a grant application to the American Institute of Ultrasound in Medicine requesting seed funding to look at the hormonal associations with growth restriction. Their contribution to my research was a turning point for me. I had always thought of myself as a clinical researcher and this was my first exploration of translational research. During my fellowship in Maternal-Fetal Medicine I collected ultrasound data on growth restricted pregnancies and sampled placentas and cord blood from the pregnancies when they delivered. What I had thought would be a one-off project became a jumping off point for continued exploration into placental biology.

Five years later, I have established a placenta bank at the University of Arizona. What was a small study focusing on just one condition has inspired the creation of a bigger project. Our residents and fellows now contribute to the bank and have the ability to answer their own questions with the samples already collected. The bank is a resource to all of us and has fostered collaborations with the University of Arizona Biorepository and the department of Animal and Comparative Biomedical Sciences. My initial work focused on changes in leptin, renin, and C-reactive protein in cord blood, but as I learned more, the objective changed to include RNA analysis of the placental tissue. We noted that the structural protein expression was different in the growth-restricted pregnancies. This has led to the proposal of a whole different model regarding the causation of preeclampsia and growth restriction.

We will wait and see how this baby does in the neonatal intensive care unit. As we go about our conservative management until the risk becomes too great to continue, it is a comfort to know we are looking for reasons; if we understand possible mechanisms better, there is the potential to mitigate or reverse the development of fetal and maternal morbidities.

 

How has ultrasound shaped your career? Has an ultrasound study led you down an unexpected path? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Meghan Hill, MBBS, is Assistant Professor at The University of Arizona College of Medicine, Department of Obstetrics & Gynecology.

Storing Blood as a Dry Powder

Did you know that blood can only be stored for up to 6 weeks when refrigerated? Because synthetic blood is not available in the clinic, blood supplies must be continually replenished from healthy donors. Even if there is a surge in blood donations at one point in time, 6 weeks later there could be shortages if continued donations do not meet the current demand. Blood can be frozen for a decade or more but significant challenges in processing blood for frozen storage limit this option to specific situations such as for rare blood types or military use. The freezing process currently utilizes high concentrations of glycerol to protect red blood cells during frozen storage but this compound must be removed prior to transfusion, and the de-glycerolization process is very sensitive and time-consuming. Therefore, most hospitals and medical centers utilize refrigeration for blood storage.

What if, instead of refrigerating or freezing blood, there was a method to freeze-dry blood for long-term storage as a dry powder, similar to the process used for astronaut food? This could enable long-term blood storage at room temperature, and when the blood is needed for transfusion the cells could be quickly re-constituted simply by adding sterile water. Not only would this offer another option for long-term storage, it would be particularly useful in situations where refrigeration or freezing is not available, such as in some remote medical centers or for the military in far-forward settings. In addition, this method could enable stockpiles of strategic blood reserves in order to maintain an adequate blood supply during disasters such as hurricanes, which disrupt blood donations.

Blood cells dried

Electron microscopy image of red blood cells after drying/rehydration following ultrasound-mediated loading with preservative compounds.

The idea of turning blood into a dry powder and then rehydrating it for transfusion may sound like science fiction, but could it become a reality? Can nature provide clues to help us solve this problem? There are many cases in history where significant scientific breakthroughs were achieved by studying nature. For example, the Wright brothers studied the characteristics of birds’ wings during flight to discover an effective design for airplane wings. Also, Alessandro Volta invented the battery after carefully studying the electric organ in torpedo fish. In the context of cell preservation, it has been found that some organisms can survive complete desiccation for long periods of time. For example, tardigrades and brine shrimp (“water bears” and “sea monkeys”) can be dried out and remain in a state that approaches “suspended animation” for decades, but when they are rehydrated they return to normal physiological function and can even reproduce. This led us to ask the question, if these complex multicellular animals can survive desiccation, why not individual red blood cells? Scientists have found that these organisms produce protective compounds, including certain sugars and proteins, which prevent damage to their membranes during drying and rehydration.

Unfortunately, human cells do not have the transporters in their membranes that enable internalization of the protective compounds found in organisms that can survive desiccation. Therefore, an active loading method is required. We realized that the process of ultrasound-mediated drug delivery via sonoporation could potentially be applied to solve this problem and enable delivery of protective compounds into human red blood cells. In the past, most ultrasound research has either ignored red blood cells or attempted to minimize sonoporation in these cells. But what if we could intentionally sonoporate red blood cells outside of the body in order to actively load them with protective compounds so that they could be stored as a dry powder at room temperature until needed for transfusion?

Our initial efforts to load red blood cells with protective compounds for storage as a dry powder have been promising. We prepared solutions containing red blood cells, preservative compounds, and microbubbles followed by treatment with B-mode ultrasound for ~60 seconds. After ultrasound treatment, the cells were freeze-dried and stored as a dried powder at room temperature (21–23 °C) for 6 weeks or longer. Cells were rehydrated with water and we measured up to 30% recovery of viable red blood cells. In addition, we performed electron microscopy imaging of the rehydrated red blood cells and observed evidence of normal biconcave-discoid shape. Our next steps involve testing the rehydrated cells in an animal model of acute hemorrhage in order to assess the function and safety of the red blood cells in vivo after dry storage at room temperature.

Research studies are currently ongoing and much more work remains to be done before clinical translation is possible, but if it is successful this approach could have a significant impact on blood supply, particularly in locations where refrigeration and freezing is not available. In addition, this approach could potentially enable dry storage of other cell products. As I consider the possibilities of this approach, I wonder if there are other things that we can learn from nature that could also transform medical practice.

 

Have you learned something else from nature that has been incorporated into your medical practice? Do you have any ideas that could potentially transform medical practice? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Jonathan Kopechek is an Assistant Professor of Bioengineering at the University of Louisville. His Twitter handle is @ProfKope.