Focused Ultrasound and the Blood-Brain Barrier

When does a barrier protect and when does it hinder? This question is central to the challenge of delivering therapeutics to the brain. For many neuropathologies, the answer is clear: there is a critical need for strategies that can allow clinicians to effectively deliver drugs to the brain. We believe focused ultrasound (FUS) has the potential to be a powerful tool in this quest.

Part of this challenge lies in the unique nature of the blood vessels in the brain. The cells that line these vessels are tightly linked together, creating a complex obstacle—called the blood-brain barrier (BBB)—that prevents the vast majority of drugs from entering the brain from the bloodstream. Throughout the years, several strategies of bypassing the BBB have been used, with limited success and many adverse effects. These range from directly inserting a needle into the brain for injections, to the administration of hyperosmotic solutions, which create gaps between cells in the BBB throughout a large volume.

In 1956, Bakay et al successfully ablated brain tumors using high-intensity FUS. In doing so, he observed that the permeability of the BBB was enhanced in the periphery of the ablated tissue. While this was exciting news for BBB enthusiasts, the necessity of damaging tissue in the process of opening the BBB was clearly unacceptable. Several decades later, this approach was successfully modified by administering microbubbles, an ultrasound contrast agent, before sonicating (Hynynen et al 2001). This made it possible to use much lower power levels to produce the desired increase in BBB permeability, thereby avoiding brain damage. By adjusting where the ultrasound energy is focused, specific brain regions can be targeted. For a few hours after treatment, drugs can be administered intravenously, bypass the BBB, and enter the neural tissue in the targeted areas.

Over the past 16 years, many preclinical studies have used FUS to increase the permeability of the BBB, delivering a wide range of therapeutic agents to the brain, from chemotherapeutics and viruses, to antibodies and stem cells. Efficacy has been demonstrated in models of Alzheimer’s disease, Parkinson’s, brain tumors, and others. Moreover, the safety of using FUS to increase BBB permeability has been tested in every commonly used laboratory animal.

The flexibility of FUS as a tool for treating neuropathologies may go beyond the delivery of drugs to the brain. Recently, FUS was shown to reduce the amount of β-amyloid plaques and improve memory deficits in the brains of transgenic mice (Burgess et al 2014, Leinenga and Gotz 2015, Jordao et al 2013).

The success of these preclinical trials has led to the initiation of 3 human trials. Two of these trials are testing the safety of increasing the permeability of the BBB in brain tumors for chemotherapy delivery, and the third is evaluating the safety and initial effectiveness of FUS in patients with early stage Alzheimer’s disease. The rapid movement towards clinical testing has been accompanied by impressive technological advancements in the equipment used to focus ultrasound through the human skull. Arrays of thousands of ultrasound transducers can be controlled to produce sound waves that travel through bone and brain, and arrive at precisely the same time in the targeted location. The sound produced by vibrating microbubbles can be detected and used to ensure the treatment is progressing as planned.

If the barrier to drug delivery to the brain can be bridged by FUS, the development of effective treatment strategies for a wide range of neuropathologies will expand. Given the clear need for such treatments and the flexibility of FUS, the recent push toward clinical testing is encouraging. The coming years will be critical in demonstrating the safety of the technique and spreading awareness. Success in these regards will go a long way in establishing FUS as an impactful tool in the fight against inflictions of the central nervous system.

 

If you deliver drugs to the brain, how do you do so? Have you found a way to permeate the blood-brain barrier using ultrasound? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Charissa Poon and Dallan McMahon are PhD students at the Institute of Biomaterials & Biomedical Engineering, University of Toronto, and the department of Medical Biophysics, University of Toronto, respectively.

Kullervo Hynynen, PhD, is professor at the department of Medical Biophysics and the Institute of Biomaterials & Biomedical Engineering, University of Toronto, and a senior scientist at Sunnybrook Research Institute in Toronto, Canada.

The Rolling Sonograms

“Hold still and keep your eye shut tight,” I instructed, as I lathered my probe with gel and placed it carefully on my model’s left eye. Having just narrowly escaped the brink of elimination, we were riding a wave of momentum. The trophy was so close we could taste it, but the final round of SonoSlam 2017 was a real-time scan-off on model patients, and our opponents had already proven their skill. Having a live audience didn’t make imaging a pupillary reflex or calculating ejection fraction any easier, and we were feeling the heat.

The day began with scans on rotating stations testing basic knowledge and technique for various organ systems. We struggled with the hepatobiliary station (turns out most teams did over the course of the day; guess we all need more practice) and the physics/knowledge station (I still don’t know how Fourier functions are used to convert sinusoidal data to Cartesian data to produce an image). Still, we put in a strong showing, and at halftime, of 27 teams, 2 of the 3 Ohio State teams placed in the top 5.

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Round 2 was trickier but more entertaining than round 1, with stations designed to test our technique and creativity. Among the highlights: identifying an image acquired by a teammate via ultrasound charades, guiding a blindfolded teammate to acquire the correct scan using nothing but verbal cues, and acquiring a biopsy sample under ultrasound guidance. These were difficult, but despite a few groans of frustration, we enjoyed ourselves as we raced through the stations. We felt so good about our performance that we even let ourselves think ahead, speculating whether we would face our teammates in the final. That changed quickly, however, with the announcement of the finalists: we had made the final, but placed third, and were the only OSU team left.

The first challenge of the finals was Dr. Boulger’s favorite ultrasound game, the peel-and-reveal. Tiles filling the screen are removed one by one until someone correctly guesses the image underneath, with more points awarded the more tiles remained. Any hesitation or uncertainty meant more points for the competition, and only the top 2 teams would survive till the second round. Watching the other teams grab an early lead, we sweated bullets as we clawed our way back, only to fall behind again with a premature guess. It was neck-and-neck till the very end, when a gutsy call of McConnell’s sign from Sam edged us into second place. We collapsed back into our chairs in relief, and our attendings, watching from the back, let out their collective breath, probably.

For the final challenge, each team sent a representative to scan on live models behind a closed curtain, with their screens displayed for the audience to see. Each team member had to scan twice, and the audience would vote on the better image by way of cheers and applause. They were also allowed to give advice to the scanners, which meant the auditorium soon became a pandemonium of shouted instructions. Objectives included cardiac output and bladder calculations, MSK ultrasound, and ocular imaging. This time we took the early lead thanks to Charles’ affinity for shoulder scans, but quickly ran into setbacks as well (hard to measure bladder volume when the patient had just peed). We managed to keep up our momentum, however, and after 6 nerve-wracking rounds, we edged our opponents 4-2, clinching the SonoSlam championship for Ohio State for the second time.

Looking back on the day’s events, I am proud of our team’s accomplishments but also impressed with the competition. We have great mentors and almost a decade of ultrasound experience between the 3 of us, but some of the other teams were no less strong, and frankly we were very fortunate to take home the title. To me, this means a bright future for ultrasound education, as medical students across the country are learning valuable skills that will put them in good stead for residency and beyond. More importantly, it means that next year’s teams will have to step up their game, as Ohio State must now defend its title as 2-time SonoSlam champion. No pressure, guys.

 

Have you participated in SomoSlam? If so, tell us about your experience. Comment below or let us know on Twitter: @AIUM_Ultrasound.

The 2017 SonoSlam champions, The Rolling Sonograms, was composed of Samatha King, Charles McCombs, and Jeffrey Yu. Samantha King is a fourth year medical student from the Ohio State University College of Medicine planning to pursue a career in emergency medicine. Charles McCombs is a third year medical student at the Ohio State University College of Medicine and hopes to end up in pediatrics and/or emergency medicine. Jeffrey Yu is an anesthesiology PGY-1 at the Ohio State University Wexner Medical Center.

 

 

Internal Medicine and Bedside Ultrasound–A Match Made in Heaven

I am an internist who does bedside ultrasound. This has not always been true. From 1986, when I got my MD from Johns Hopkins School of Medicine, to November 2011, I was a traditional internist, taking care of a panel of patients in a small university town in Idaho. I saw my patients in the office when they could walk or wheel in with their problems and in the hospital when they were sicker. I took call for my partners on rotating weekends and holidays. I occasionally ordered ultrasounds and echocardiograms and thought of them as blurry representations of internal structures that could be magically interpreted by radiologists.

In 2011, events such as the growing up of our 2 children allowed me to reconsider my choices of what to do with my MD. I had always wanted to do medicine in resource-poor settings overseas. I had often been curious about locum tenens work in other states, which would involve adventure and exposure to new practice styles and surprisingly generous compensation compared to my predominantly outpatient practice. I also had an urge to binge on continuing medical education courses, which I had denied myself for years due to responsibilities at home.

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One of the CME courses I treated myself to was an introductory course in emergency ultrasound through Harvard/Massachusetts General Hospital. It was wonderfully taught and I was immediately hooked. Ultrasound at the bedside would transform my practice and had the potential to transform the whole practice of internal medicine! The Cupid of bedside ultrasound had sunk his arrow straight between my eyes.

I went on to take more courses in bedside ultrasound both in person and online and bought myself a small pocket ultrasound which rapidly developed my imaging skills. I began to use ultrasound clinically as a diagnostic tool within weeks of my first exposure. I discovered over-expanded bladders, failing hearts, pleural effusions, ascites, or lack thereof in my patients with big bellies. I became a better doctor, and enjoyed my job more. My patients were happy to have benefitted from what looked to them like Star Trek technology.

I expected at any point that someone in the diverse hospitals where I served as a locum tenens hospitalist would ask for my credentials or forbid me to use ultrasound. I expected skepticism by cardiologists with whom I worked. I expected radiologists to be upset at me. I even did a 1-month UC Irvine mini-fellowship and ARDMS certification as a sonographer. These experiences gave me a vast amount more expertise and confidence, but were mostly to ward off imagined disapproval. Yet nobody ever made me present my certification. Nobody disapproved to my face except one radiologist, who I’m still working on. Cardiology consultants were tickled to get imaging information in addition to history and vital signs. I may have benefitted from being in hospitals where people were too busy taking care of patients to fuss with me. It really seemed, though, that the vast majority of people with whom I worked realized that I was a better doctor with an ultrasound than without.

I have gone on to teach bedside ultrasound and participate in research on malaria and schistosomiasis with medical students in Tanzania. I have taught basic ultrasound to overburdened healthcare workers and physicians from Doctors Without Borders in South Sudan during its ongoing civil war. Knowing how to teach basic bedside ultrasound means I am valuable in resource poor settings even if I can only stay for a couple of weeks. I have been able to teach my internal medicine colleagues in the US along with residents and medical students, which has been a wonderful opportunity for a nonacademic rural physician.

So what’s my point here? As an “early adopter” of bedside ultrasound in internal medicine I have made myself a test case. So far these are the results:

  1. It wasn’t too hard to learn enough ultrasound to be a better doctor.
  2. There was never a time when I was too much of a novice to benefit from bedside imaging, yet every time I ultrasound a patient I learn something new. I can’t foresee a time when my learning will be complete.
  3. There has been surprisingly little push-back and a gratifying amount of appreciation.
  4. Bedside ultrasound is the perfect extension of the physical exam in internal medicine. It brought back my joy in physical diagnosis. We should all be doing it!

 

Have you used ultrasound in your internal medicine practice? Have you gone after ultrasound education after obtaining your degree? How can medical education be modified to encourage the widespread use of ultrasound by future internists? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Janice Boughton, MD, is an internist working as a staff Hospitalist at Gritman Medical center as well as is a locum tenens physician at other northwest hospitals. She also supervises and serves in rural health clinics, and blogs about bedside ultrasound and other issues at http://whyisamericanhealthcaresoexpensive.blogspot.com/?m=1.

The National Ultrasound Interest Group (NUSIG)

The National Ultrasound Interest Group (NUSIG) is a student-led organization founded in 2014 to promote ultrasound in undergraduate medical education. You may know us as the force behind planning national level events like SonoSlam. The bulk of NUSIG’s work, however, is sharing education and leadership resources between Ultrasound Interest Groups (USIGs) across the country. Each of the five regional representatives contact medical schools in their areas to exchange ideas, plan co-sponsored events, and see how NUSIG can assist them in evangelizing ultrasound.

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NUSIG provides everything from information on getting equipment and funding, to original educational content. Our podcast on iTunes (quickly closing on the 1,000 download mark) currently features a journal club series. Each episode is hosted by a different school evaluating an ultrasound-related article.

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Our next series is how to plan an Ultrafest, where we interview schools experienced in putting on these events. Our hope is that these USIGs can learn from each other, and other schools might be inspired to start their own UltraFest once it’s been laid out how. In the future, we aim to collect medical student level ultrasound lectures from across the country and publish them for anyone to view. Our vision is to serve as a central repository for the best medical student educational content available. Lastly, our twitter feed regularly features current ultrasound research articles, and retweets outstanding free open access medical education content.

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If you want to learn more about us or get involved, check out our website at www.nationalusig.com, and follow us on twitter and Facebook @NtlUSIG. You can find us on iTunes by searching for “NUSIG podcast.”

Are you a member of the National Ultrasound Interest Group? Did you attend this year’s SonoSlam? If so, share your thoughts and feedback. Comment below or let us know on Twitter: @AIUM_Ultrasound.

Mat Goebel is in charge of Social Media for the National Ultrasound Interest Group and is a medical student at University of California at San Diego.

Excellence in Education

It is an honor to receive the 2017 Peter H. Arger, MD, Excellence in Medical Student Education Award. I am fortunate to know Dr. Arger and recognize his remarkable achievements in education, accreditation, and leadership in ultrasound. It’s my great privilege to work with different students, whether they are medical students, residents, fellows, sonography students, vascular technology students, or physicians of different medical specialties. I have had many great teachers and mentors toJohn_Pellerito learn from. Some of my favorite teachers like Barry Goldberg, Ken Taylor, Chris Merritt, and Peter Arger have the gift to communicate complex ideas and make them simple and easy to understand. Teachers at that level inspire me to be the best I can be.

I know there are many educators who understand that feeling when a student “gets it.” The anatomy and physiology that they’ve been studying comes to life. When the ultrasound unit is no longer a confusing mess of dials and buttons and becomes a window into the human body. When they realize that in their hands, ultrasound can make a difference in patient care.

I am lucky to work with  a team of physicians and sonographers who enjoy teaching our medical students. We meet to devise new ways to integrate ultrasound into our longitudinal 4-year ultrasound program. One of the techniques we use to engage our students is to integrate games into our classes. Our SONICS (SONographic Integration of Clinical skills and Structure) faculty has enjoyed putting together ultrasound games for our students. We find that gaming increases their excitement and takes advantage of their competitive edge. One of our latest creations, the Hunger Games (J Ultrasound Med 2017; 36:361–365), has proven very successful.

During this class, we ask one member of each student team to fast prior to a scan of the gallbladder and mesenteric arteries. Following a breakfast of a bagel and cream cheese, the students are rescanned to assess for changes in gallbladder size and mesenteric blood flow. All scanning is performed by the students with faculty guidance. One team is deemed the “winner” and awards are given. The session combines both anatomic and physiologic principles to learn about gastrointestinal and vascular function and incorporate Doppler techniques. This activity provides the foundation for a powerful integration of Doppler ultrasound into medical education.

What are some of the ways that you have engaged your students with fun and interactive ultrasound programs? Do you have any stories from your own education to share? Comment below or let us know on Twitter: @AIUM_Ultrasound.

John S. Pellerito, MD, is professor of Radiology at Hofstra Northwell School of Medicine and Vice Chairman of Radiology at Northwell Health.

SonoSlam 2017

16SonoSlam_logoIf you attended the AIUM convention the past 2 years you may have heard mention of SonoSlam in passing. So what is it? SonoSlam is a medical student ultrasound competition and educational event. It was conceived as an idea to promote medical student ultrasound and was officially born in Orlando in 2015. A few members of the medical education committee were discussing how to get students more engaged in ultrasound at the national level. A national ultrasound student interest group had been formed and got behind the idea of nationalizing ultrasound activities for medical students. Many of us had been involved in regional events such as Ultrafest or had participated in Sonogames™, an emergency medicine resident ultrasound competition. As we brainstormed, SonoSlam came to fruition. We wanted this event to be more than a game, making sure to integrate education into the proceedings. Given the diversity of exposure to ultrasound in undergraduate medical education, the faculty wanted to ensure that this event would be appealing to students of all levels of experience. In addition, the unique offering of AIUM is that this event would be multidisciplinary. With these key components of education, competition, and a multidisciplinary approach SonoSlam was created. The inaugural SonoSlam was held in New York in 2016 with the winning team awarded the Peter Arger Cup, named after the famed radiologist who championed medical student ultrasound education at the AIUM. Seventeen teams from 12 different schools participated in this inaugural event with more than 30 faculty from across the country. This year in Orlando we grew to 23 teams from 17 schools from across the country—Oregon to New York to Florida and all in between. We had more than 50 faculty from a multitude of specialties, including emergency medicine, internal medicine, critical care, obstetrics and gynecology, radiology, and pediatrics. We plan to continue to host this event annually with the lofty goal of having representation from every medical school in the country. We hope to see you in New York March 24, 2018!

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For more information about SonoSlam or if you are interested getting involved please email us: sonoslam@gmail.com.

Written by Creagh Boulger, Rachel Liu, and Dave Bahner. Creagh Boulger, MD, RDMS, FACEP, is Assistant Professor, Assistant Director of Ultrasound, and Assistant Fellowship Director of Emergency Ultrasound at Ohio State University Wexner Medical Center. Rachel Liu, BAO, MBBCh, is Assistant Professor of Emergency Medicine and Director of Point-of-Care Ultrasound Education at Yale University School of Medicine. Dave Bahner, MD, RDMS, FAIUM, FAAEM, FACEP, is Professor and Director of Ultrasound, Fellowship Director, Investigator, and Core Faculty at Ohio State University.

How do you make ultrasound education engaging? Do you have any ideas for bringing students from across the country together? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Life Hacks for the 2017 AIUM Annual Convention

Are you ready? The 2017 AIUM Annual Convention is in less than 2 weeks and we have been working hard to make this a great multidisciplinary convention just for you. If you haven’t registered, do so here. If you are already heading to Orlando, here are a few things you can do to get the most out of your experience:

  1. Plan

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View the Program online and create a personalized schedule.

 

  1. Go

Transportation

There are several options to get to and from the Orlando Airport and the Swan and Dolphin Resort. The AIUM has negotiated a special discount with Mears, or you can choose from other options here.

 

  1. Surf

WiFi

Surf the web via complimentary Internet access throughout the convention space. In addition, if you are staying at the Swan and Dolphin Resort, your resort fee includes in-room Internet access.

 

  1. Follow

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Stay in the know by following the AIUM and the Convention on Twitter (#AIUM17), Instagram (aium_ultrasound), vimeo, LinkedIn, and Facebook as we share news and events, as well as photos and videos.

 

  1. Listen

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Join the world-class faculty and ultrasound luminaries in any of the many sessions, presentations, and events that are occurring at any given time during the convention. Check out your many options on the AIUM convention web site.

 

  1. Learn

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Attend any of the 150+ sessions from 19 different interest tracks, with courses specifically designed for novice through advanced:

  • View and discuss unique cases with the physicians who made the diagnoses in any of the Just Images Sessions.
  • Attend courses developed by community and interest group officers in Special Interest Sessions.
  • Watch as a group of expert panelists evaluate new and challenging cases in Film Panel Sessions.
  • Learn about the latest research in Research Abstract Presentation Sessions.
  • View E-posters.
  • Meet with other ultrasound professionals who share your interests, plan future AIUM educational programs, and discuss the issues in your specialty in Community and Interest Group Meetings.

 

  1. Diagnose

 Case

The ever popular Case-of-the-day Challenge has become Image Challenges and will be located on the Exhibit Hall floor (Atlantic Hall B/C), on Sunday, March 26, through Wednesday, March 29, 2017.

 

  1. Earn

CME    blue arrow   Earn up to 7.5 CME credits during the Preconvention and 27.25 CME credits during the Convention.

ARRT   blue arrow   Earn up to 7.5 ARRT credits during the Preconvention and 27.25 ARRT credits during the Convention.

SAMs   blue arrow  The American Board of Radiology (ABR) has approved 6 Self-Assessment Modules (SAMs) activities from our upcoming 2017 Convention.

UGRA   blue arrow  One session at the Preconvention and 8 sessions at the Convention have been added to the UGRA Portfolio program’s course offerings.

 

  1. Eat

 Disney Eateries

Check out all of the conveniently located places you can get dinner or a quick bite. Just within the Walt Disney World Swan and Dolphin Resort if you want some Italian for dinner, try Il Mulino, located in the Swan, or if you want something else, try Shula’s Steak House (in the Dolphin), Kimonos (Japanese cuisine; in the Swan), or Todd English’s Bluezoo (seafood; in the Dolphin), but be sure to make your reservations now to avoid a long wait as they can all be very popular. There are also 7 more options for more casual or quicker bites so you never have to go very far to find something, and you will be able to purchase lunch on the Exhibit Hall floor.

 

  1. Play 

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Registered attendees can buy discounted tickets to Walt Disney World Theme Parks. But hurry: the discount ends Friday, March 24, 2017, at 9 pm.

We can’t wait to see you in Orlando! Don’t forget to tag and share #AIUM17 on social media.