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Serendipity in the Echo Lab

2024; Elsevier BV; Volume: 8; Issue: 5 Linguagem: Inglês

10.1016/j.case.2024.04.001

2468-6441

Vincent L. Sorrell,

Microfluidic and Capillary Electrophoresis Applications

Some'll win, some will lose; Some are born to sing the blues; Oh, the movie never ends; It goes on and on and on and on. (1981; Don't Stop Believin'. Jonathan Cain, Steve Perry, Neal Schon for Journey) We are all products of where we come from. This concept is never far from my conscious mind when I am reading echo studies. Echo technology, which seems so mature and sophisticated, has greatly evolved over the past seven decades. The echo studies I read today are vastly superior to those I read only a few years before. But, as Journey reminds us, the movie never ends… it goes on and on. How exciting to muse over this Journey and think about what the echo studies of our students' students will eventually look like. My goal for this editorial is to help you learn about some of the developments along the way and better understand the important role that serendipity played in those advances. I will also bring you some fun stories away from echo that address other accidental discoveries. By doing so, I hope you remain vigilant in your own journey since the finding you see on an echo today may be the nidus for the next big technical or clinical advancement. Undeniably, this surprising discovery will only happen if you recognize your finding for the importance it offers and then start to study that finding (note: one method to begin that study is through global recognition and feedback, such as submitting your finding as a case report to CASE). Isaac Newton discovered the concept we know as gravity while pondering an apple falling from a tree. Certainly, other really smart people had seen apples fall long before Newton did. Archimedes discovered the way to calculate the volume of irregular objects by watching the water level rise when he stepped into his evening bath. Once again, this was a very simple observation that many experienced, but it was Newton and Archimedes who submitted their findings to a scientific community, like via CASE. In the 18th century (c. 1754), Horace Walpole (the 4th Earl of Oxford; an art historian, among other recognitions) is credited with coining the term "serendipity" which he used to describe a discovery made by accident. In a letter written to Sir Horace Mann (a British diplomat), he described an unexpected discovery of an important Renaissance painting by referencing his fortune to the Persian fable of the Three Princes of Serendip (the ancient Persian name of Sri Lanka [Ceylon]), who were known to travel around the world continuously, while accidentally discovering things unsought.1Zafarris J. The etymology of "serendipity". Useless etymology.https://uselessetymology.com/2017/12/02/the-etymology-of-serendipity/Date: 2017Date accessed: March 29, 2024Google Scholar There are many amazing stories that demonstrate the impact of serendipity. In preparation for this editorial, I learned that your morning coffee warrants a thank you to a herd of energetic goats; that our delicious brownies resulted from a forgotten ingredient; and with a slight chuckle, someone likely got the fright of their life when they discovered that corn could pop. It's true that accidental discoveries resulted in some very well-known culinary delights.2Farinetti O, Mc Gilvray B. Serendipity: from truffles and champagne to corn flakes and coffee: stories of accidental success, Audiobook, Blackstone Publishing; Ashland, OR.Google Scholar These discoveries serve to remind us that our mistakes and our failures may become the most essential ingredients in our successes. An important common finding in these discoveries is that repeated experimentation is necessary to proceed from a lucky observation to a well-understood finding. Each of these innovations highlights the importance of allowing researchers enough time to investigate those serendipitous observations. Protected time for critical thinking will remain at the forefront of the most successful academic programs. There are so many things important to our everyday lives that are credited as having been discovered by accident: penicillin, Teflon, nylon, Velcro, sugar substitutes, and something that seemed like a good idea at the time, but we should all wish had never been invented: plastic. Similarly, much scientific knowledge came to light through chance including the theories of gravitation, big bang, DNA, the Rosetta Stone, and the Dead Sea Scrolls, to name but a few.3Roberts R.M. Serendipity: accidental discoveries in science. Wiley, Hoboken, NJ1989Google Scholar W. C. Roentgen accidentally discovered unknown rays that were able to pass through screens (thus, calling them X-rays) a little over a century ago (1895). He was not the first person to see these strange effects and other researchers had briefly noticed them earlier. Roentgen, however, thought that these effects were worth studying and he carefully documented many different aspects of these new rays and published his work to encourage ongoing research (NOTE: I wish CASE was around at that time). Roentgen's groundbreaking discovery was a result of the initial serendipitous observation combined with subsequent investigation of the anomaly. That discovery started the field of radiology and it was within ONLY one year when the first patient was treated with radiotherapy (1896), after seeing skin erythema would occur when taking these pictures.4Tubiana M. Wilhelm Conrad Röntgen et la découverte des rayons X [Wilhelm Conrad Röntgen and the discovery of X-rays].Bull Acad Natl Mzed. 1996; 180 (French): 97-108Google Scholar Wilson Greatbatch accidentally discovered pacemakers. As I understand it, he was working on an oscillator to record the human heart (building it from scratch) when he inadvertently attached the wrong resistor causing the oscillator to produce a series of electrical pulses instead of its desired goal of reading a steady signal. This error meant that this device was stimulating the heartbeat instead of recording it. To be clear, though, the pacemaker was NOT established solely because of this error, but to a much greater degree because the inquisitive Greatbatch had the brilliant idea that maybe this broken oscillator could be used to regulate the heartbeat of people in need. He continued to study and refine his invention, then in 1960, he successfully implanted his refined pacemaker into a dog and it worked perfectly. (Then, as all great minds were driven to do in that era, he tested this device on himself and demonstrated that it could regulate his own heartbeat). In 1961, after a series of failed presentations to various manufacturers, he convinced a start-up company (Medtronic) to invest in his accidental discovery. The serendipitous pacemaker was approved by the FDA in 1962 and the rest is history.5Beck H. Boden W.E. Patibandla S. Kireyev D. Gutpa V. Campagna F. Cain M.E. Marine J.E. 50th anniversary of the first successful permanent pacemaker implantation in the United States: historical review and future directions.Am J Cardiol. 2010; 106: 810-818Google Scholar Maybe you are more familiar with the story of penicillin which was accidentally discovered by Sir Alexander Fleming? As I understand it, after returning from holiday and finding that a Petri dish with staphylococcus culture had been unintentionally kept out of an incubator allowing it to become infected by a Penicillium mold, he noticed that no bacteria grew near it. If the incubator had been used, only the bacteria would have grown, and we might still be waiting on the perfect conditions for this serendipitous discovery.6Discussion on penicillin.Proc R Soc Med. 1944; 37: 101-112Google Scholar Our early understanding of ultrasound starts with Lazzaro Spallanzani (1729–1799) who was investigating how bats could fly in the dark. Through careful experimentation, he demonstrated that when blinded, a bat could carefully maneuver through space, but when deaf, even if only in one ear, this skill was lost. Those findings resulted in his hypothesis that bats use sound, not sight, to steer and this was later consolidated into the concept of echolocation.7Griffin D.R. Galambos R. The sensory basis of obstacle avoidance by flying bats.J Exp Zool. 1941; 86: 481-506Google Scholar,8Kaproth-Joslin K.A. Nicola R. Dogra V.S. The history of US: from bats and boats to the bedside and beyond: RSNA centennial article.Radiographics. 2015; 35: 960-970Google Scholar In one of my favorite experiments of all time, Jean-Daniel Colladon (Swiss physicist) and his assistant Jacques Charles-Francois Sturm proved that sound travels faster in water than in air. These researchers hung a large church bell off the side of one boat and a trumpet-like device off the side of another boat 10 miles away (Figure 1). At the same time they rung the underwater bell, they ignited gunpowder to make a loud explosion in the air. Amazingly, and the reason this is one of my all-time favorite experiments, they were able to measure the speed of sound in water as 1,435 m/sec (which is remarkably similar to the value we should all be familiar with: 1,482 m/sec).9Colladon J.D. Sturm F.K. The compression of liquids. IV. Speed of sound in liquids [in French].Ann Chim Phys Ser. 1827; 2: 236-257Google Scholar So, now that history recognizes the importance of sound in nature and can measure its speed through various media, we need a method to create consistent ultrasound waves. That is where Pierre Curie, a French physicist co-awarded the Nobel Prize for Physics in 1903 with his (more famous) wife Marie Curie and colleague Henri Becquerel, comes into this story. In addition to their joint discovery of radium, Pierre is credited with the detection of piezoelectricity during research with his brother, Jacques Curie (1878–1880). Piezo means to press (Ancient Greek). These researchers invented the quartz piezoelectrometer, now considered to be the first practical application of the piezoelectric effect (used by Marie Curie to measure radium's miniscule electrical charges).10Mould R.F. Pierre Curie, 1859–1906.Curr Oncol. 2007; 14: 74-82Google Scholar Did you know that ultrasound imaging is the only major medical imaging modality for which no-one has been awarded a Nobel Prize (yet)? Although this Editor has thought about crowdsourcing for Christian Doppler, I realize that it would be difficult for the nominating committee to establish Nobel precedence since the development of medical ultrasound (especially for the beating heart) has depended on so many prior insights from physics, realigned initial technical developments, variable preliminary clinical experiments and major advancements from close collaborations between engineers and clinical scientists. For more on the fascinating history of echocardiography from pioneers in this field, read the 23rd ASE annual Feigenbaum lecture from Drs. Alan S. Pearlman and Harvey Feigenbaum.11Pearlman A.S. Feigenbaum H. 23rd annual feigenbaum lecture: history of echocardiography: a personal perspective.J Am Soc Echocardiogr. 2022; 35: 1202-1213Google Scholar I wonder if any CASE readers recall as vividly as I do the very first time they injected an ultrasound enhancing agent into a peripheral vein with the expectation it would show up in the left heart. I was fascinated by this incredible concept. To this day, I remember the patient's indication for the echo, the room and clinical environment it was performed in, the US system that was used (note: it was an HP 1500) and the sonographer (aka researcher) who was working with me. At that point in my career, any material injected intravenously (e.g. medications, saline flush, agitated saline bubbles) would've only been seen in the left heart if there was a shunt. However, as purported by the manufacturers of this first-generation echo contrast agent (sonicated albumin; Albunex12Christiansen C. Kryvi H. Sontum P.C. Skotland T. Physical and biochemical characterization of albunex, a new ultrasound contrast agent consisting of air-filled albumin microspheres suspended in a solution of human albumin.Biotechnol Appl Biochem. 1994; 19: 307-320Google Scholar), I was prepared to visualize enhancement of the left ventricular cavity. Although it was really short-lived (only visible in the LV for 3-4 beats) and if I showed you that echo today, you'd be deeply disappointed, I was totally fascinated. I anticipated the awesome potential of LV contrast enhancement and this event served in part to foster my scientific journey of discovery that remains today. Contrast echocardiography has been attributed to begin at the University of Rochester (NY) by Gramiak and Shah during an accidental observation. Yes, it was serendipitous. After the injection of indocyanine green dye (a commonly employed method to estimate the cardiac output), these investigators unexpectantly witnessed large clouds on the echocardiographic display. Their observations were subsequently carefully studied at a time when echocardiography was still in its infancy.13Gramiak R. Shah P.M. Echocardiography of the aortic root.Invest Radiol. 1968; 3: 356-366Google Scholar During the development of the next generation of manufactured ultrasound agents, engineers created new techniques to accentuate contrast visualization within the myocardium using 2nd harmonic imaging instead of conventional fundamental modes. Since contrast bubbles resonate within the ultrasound field, whereas myocardium does not, engineers emphasized the 'second' resonating harmonic signal and filtered the 'fundamental' signal as a means to improve the signal to noise ratio.14Nanda N.C. History of echocardiographic contrast agents.Clin Cardiol. 2009; 20: 7-11Google Scholar This story of the origin of harmonic imaging will serve as my last example of serendipity in the echo lab. My colleagues and I quickly appreciated that the quality of the 2D echo image was improved even before the administration of this contrast agent. But this improved 2D image was totally unexpected and resulted in many interesting conversations between clinicians (reading the 'improved' images) and engineers (questioning if they were really 'improved'). Today, we use 2nd harmonic imaging as our default ultrasound system setting since this technique improves the near field and lateral wall endocardial definition, despite the fact that this observation was totally unexpected. (Note: watch for a future editorial on why this is so). This editorial is not intended to overlook Carl Helmuth Hertz, Inge Edler, Liv Hatle, Yoshida and Shigeo Satomura, or Harvey Feigenbaum, but my hope is that their stories are already well-known to CASE readers. I might point out that serendip is not only used for scientific discoveries, but all manners of life and love. A great example is from Inge Edler who planned to enter his chosen field of dentistry studies (following in the footsteps of his elder sister), but applied too late and had to settle for a gap-year of training in medical school instead. Of course, as fate had it, he went on to an illustrious medical career, founding many of the concepts discussed regarding the application of medical ultrasound (and he also found the love of his life at this school).15Singh S. Goyal A. The origin of echocardiography: a tribute to inge edler.Tex Heart Inst J. 2007; 34: 431-438Google Scholar If you'd like to learn more regarding the Evolution of Echo from the words of Harvey Feigenbaum, who poetically compares our appetite for borrowing nature's sophisticated use of ultrasound for our own selfish use in medical imaging in the same vein as our sustained efforts to borrow nature's wings for our use in commercial flight.16Feigenbaum H. Evolution of echocardiography.Circulation. 1996; 93: 1321-1327Google Scholar In this issue of CASE, you will be treated to an atypical cause for severe aortic stenosis – rheumatic heart disease – by Alizadeh et al. Also in the Doppler Dilemmas section, Buck et al. highlight an atypical cause for aortic regurgitation and Shin et al. report on a rare acquired Gerbode-type shunt from endocarditis. In a beautiful example of serendipity in the echo lab, Numata et al. do a fabulous job of showing the readers their accidental discovery of a Rare but Deadly Finding: a mushroom-shaped RVOT as an early clue in pediatric ARVC (arrhythmogenic right ventricular cardiomyopathy). The authors bring you along their journey of discovery as they apply their serendipitous finding to their CASE files to highlight its relevance. Finally, Soudah et al. report on another deadly finding – type A aortic dissection – and emphasize the importance of making a rapid diagnosis through multimodality imaging. I have vastly enjoyed reading submissions to CASE from across the globe that reiterate this concept of Serendipity in the Echo Lab as authors expand our understanding of the value of echocardiography applied in novel and unexpected ways. It would be inconceivable to think that Newton was the first to witness an apple fall from a tree or that the "Eureka!" moment of naked excitement discovered by Archimedes was truly original. The most important tools for successful serendipity included curiosity, knowledge, training, creativity and coincidence. Although we are all products of where we come from, and echo is no stranger to serendipity, we should follow the advice of Journey and don't stop believin'. Keep this in mind as you read your next echo so you will be prepared for your own Eureka moment (but, when you do, do not react exactly like Archimedes). Remember, every echo you see today has a teaching point; and every teaching point is a potential new CASE report!