ISNE Honors

Willem Einthoven - 1895 - ISNE Gold Medal

Willem Einthoven (21 May 1860 – 29 September 1927) was a Dutch physician and physiologist. He invented the first practical electrocardiogram (ECG or EKG) in 1895 and received the Nobel Prize in Physiology or Medicine in 1924 for it ("for the discovery of the mechanism of the electrocardiogram").

Before Einthoven's time, it was known that the beating of the heart produced electrical currents, but the instruments of the time could not accurately measure this phenomenon without placing electrodes directly on the heart. Beginning in 1901, Einthoven completed a series of prototypes of a string galvanometer. This device used a very thin filament of conductive wire passing between very strong electromagnets. When a current passed through the filament, the magnetic field created by the current would cause the string to move. A light shining on the string would cast a shadow on a moving roll of photographic paper, thus forming a continuous curve showing the movement of the string. The original machine required water cooling for the powerful electromagnets, required five people to operate it and weighed some 270 kilograms. This device increased the sensitivity of the standard galvanometer so that the electrical activity of the heart could be measured despite the insulation of flesh and bones.

An early ECG device

Although later technological advances brought about better and more portable EKG devices, much of the terminology used in describing an EKG originated with Einthoven. His assignment of the letters P, Q, R, S and T to the various deflections are still used. The term Einthoven's triangle is named after him. It refers to the imaginary inverted equilateral triangle centered on the chest and the points being the standard leads on the arms and leg.

After his development of the string galvanometer, Einthoven went on to describe the electrocardiographic features of a number of cardiovascular disorders. Later in life, Einthoven turned his attention to the study of acoustics, particularly heart sounds which he researched with Dr. P. Battaerd.

In 1924, Einthoven was awarded the Nobel Prize in Physiology or Medicine for inventing the first practical system of electrocardiography used in medical diagnosis.

Floyd Alburn Firestone - Medical Ultrasonography - 1942 - ISNE Gold Medal

Floyd Alburn Firestone (1898–1986) was an acoustical physicist, who in 1940 while a professor at the University of Michigan invented the first practical ultrasonic testing method and apparatus. He was granted US Patent 2,280,226 for the invention in 1942. Manufactured by Sperry Corporation, the testing device was known variously as the Firestone-Sperry Reflectoscope, the Sperry Ultrasonic Reflectoscope, the Sperry Reflectoscope and sometimes also just as a Supersonic Reflectoscope, the name Firestone had originally coined for the instrument; the technology is not just used in quality control in factories to reject defective parts before shipment, but also revolutionized transportation safety. For example, ultrasonic testing is used for safety maintenance inspection of railroad cars, particularly axles and wheels, aircraft, particularly fuselages, and other transportation vessels for material fatigue. Dr. Firestone’s ultrasonic pulse echo technique for metal defect testing was also later applied in medical diagnosis, giving birth to the field of Echocardiography and to the field of Medical Ultrasonography, generally Dr. Firestone was the editor of the Journal of the Acoustical Society of America from 1939-1957. Among Firestone’s many other inventions in his field are in a single year an “automatic device for the minute inspection of flaws”, “a new and useful improvement in hook-up of electrical apparatus”, and “a device for measuring noise”, and, even, later a “musical typewriter”.

In 1933 Firestone proposed an alternative to the mechanical-electrical analogy of James Clerk Maxwell in which force is made the analogy of voltage (the impedance analogy). Firestone's analogy (now called the mobility analogy) makes force the analogy of current. In this work he introduced the concept of "through" and "across" variables and demonstrated that there were analogies for these variables in other energy domains, making it possible to treat a complex system as a unified whole in analysis. Firestone's analogy became popular amongst mechanical filter designers because it has the property of preserving network topologies when transforming between the mechanical and electrical domains.

Image Caption: First human brain scan by Computerized Tomography (1969)

HOUNSFIELD and AMBROSE - 1969 - ISNE Gold Medal

WHEN HOUNSFIELD MET AMBROSE, THE INVENTION OF COMPUTED TOMOGRAPHY


BY DUSTIN GRINNELL

In 1969, Dr. James Ambrose, a neuroradiologist from Atkinson Morley’s Hospital in London, got a call from an engineer he had never met named Godfrey Hounsfield from EMI laboratories. Inspired from an idea which struck him on vacation, Hounsfield called Ambrose to introduce him to his recent work, reconstructing a 3D image of a box by considering it as a series of slices.

During their phone call, Hounsfield–already dismissed as a “crank” by many renowned radiologists–proposed an imaging device far superior to the commonly used X-ray machine, which produced fuzzy 2D pictures of brain structures. Like other radiologists Hounsfield had contacted, Ambrose dismissed Hounsfield’s ideas at first, but later–albeit reluctantly–agreed to a meeting. That eventual get-together led to the first Computed Tomography (CT) scanner, a machine that revolutionized diagnostic medicine and the way we look inside the brain.

Godfrey Hounsfield, the youngest of five children, was a tinkerer early on. Recollecting his childhood, set on his parent’s farm, he said, “I enjoyed the freedom of a rather isolated country life.” When he was a teenager, he would often take apart electronics, building tools and devices. He once built a rudimentary hang glider which he flew off stacks of hay behind his house, almost killing himself many times he later said of the memory. At the Magnus Grammar School, he showed strengths in math and physics. After graduation, he joined the Royal Air Force just before World War II, learning electronics and radar while he completed his service. He later studied electrical and mechanical engineering at the Faraday House in London and in 1951 joined the Central Research Laboratory at EMI laboratories where he worked on weapons systems and radar. It wasn’t until 1960 that he took an interest in computer technology and eventually imaging. When he called Ambrose in 1969, Hounsfield had already built a prototype of his invention, the first Computed Tomography scanner.

Tomography, the Greek word tomos means “slice” or “section.” Graphia means “describing.” Unlike an X-ray machine, which produces flat, 2D pictures of bone and tissues, Hounsfield’s device took multiple, thin photographic slices of objects, which could be later combined on a computer to create three-dimensional composite images.

In the late 60’s, working on a meager research budget of less than $40,000, Hounsfield and his team of three–an electronics expert, programmer and mechanic–built a prototype CT scanner on a lathe bed, overcoming repeated failed tries during development. “As expected,” Hounsfield said, “The program involved many frustrations, occasional awareness of achievement when particular technical hurdles were overcome, and some amusing incidents.”

Hounsfield’s early photographs were of pig bodies and human brains. His team’s first scanner took nine days to capture a full 3D image and worked by rotating around an object 1 degree at a time for 160 traverses, emitting gamma rays as its light source. Hounsfield later switched the energy source to x-rays, reducing the scanning time to 9 hours.

While the idea seemed promising to Dr. Ambrose on first meeting Hounsfield, the radiologist remembered Hounsfield’s presentation as vague, containing more promises than proof. “The conversation was…difficult,” Ambrose said looking back on the day. But Ambrose allowed Hounsfield to prove himself, sending a human brain from a local museum to EMI Laboratories. Five weeks later, Ambrose received the first brain images produced from a CT (See Picture). Immediately, he knew the field of medical imaging was changed forever.

Hounsfield and Ambrose began a lifelong partnership, working together to build a CT prototype for clinical use. In the beginning, their operation almost ended several times because of money issues, but a doctor at the Department of Health placed an early order for a machine, injecting the project with enough cash to continue.

In 1971, with enough funding and four newly built scanners, Hounsfield and Ambrose photographed the brain of patient with a frontal lobe tumor. “It looks exactly like the picture,” the surgeon remarked, referring to the tumor’s appearance on the scan. From 1973 to 1976, head-scanning CT machines were distributed to hospitals in England and the United States (whole-body scanners in 1976).

For their contribution to medical science, Hounsfield and Ambrose jointly won the BJR Barclay prize in the 1974. A year later, Hounsfield was elected to the Royal Society and in 1979 was awarded the Nobel Prize in Physiology and Medicine. Two years following the Nobel, he was honored with knighthood, becoming Sir Godfrey Hounsfield.

It was in 1972, at the 32nd Congress of the British Institute of Radiology, where Hounsfield and Ambrose first presented brain scans generated by CT in their talk, Computerised Axial Tomography–a presentation many audience members say they will never forget. Today, there are over 6,000 scanners in the US; 30,000 worldwide. In 2004, Godfrey Hounsfield passed away at the age of 84, leaving behind one of the most important inventions in medical science history.

References:

  1. http://bjr.birjournals.org/content/79/937/5.full.pdf

  2. http://www.allpsychologycareers.com/topics/neuroimaging.html#link1

  3. http://www.avmi.net/newfiles/CT/CT.html

  4. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1979/hounsfield-autobio.html

Raymond Vahan Damadian - Targeted NMR Scanner - 1971 - ISNE Gold Medal

Raymond Vahan Damadian (born March 16, 1936)

In a March 1971 paper in the journal Science, Raymond Damadian, an Armenian-American doctor and professor at the Downstate Medical Center State University of New York (SUNY), reported that tumors and normal tissue can be distinguished in vivo by nuclear magnetic resonance ("NMR"). He suggested that these differences could be used to diagnose cancer, though later research would find that these differences, while real, are too variable for diagnostic purposes. Damadian's initial methods were flawed for practical use, relying on a point-by-point scan of the entire body and using relaxation rates, which turned out not to be an effective indicator of cancerous tissue. While researching the analytical properties of magnetic resonance, Damadian created a hypothetical magnetic resonance cancer-detecting machine in 1972. He filed the first patent for such a machine, U.S. Patent 3,789,832 on March 17, 1972, which was later issued to him on February 5, 1974. Lawrence Bennett and Dr. Irwin Weisman also found in 1972 that neoplasms display different relaxation times than corresponding normal tissue. Zenuemon Abe and his colleagues applied the patent for targeted NMR scanner, U.S. Patent 3,932,805 on 1973. They published this technique in 1974. The US National Science Foundation notes "The patent included the idea of using NMR to 'scan' the human body to locate cancerous tissue." However, it did not describe a method for generating pictures from such a scan or precisely how such a scan might be done.

Damadian's research into sodium and potassium in living cells led him to his first experiments with nuclear magnetic resonance (NMR) which caused him to first propose the MR body scanner in 1969. Damadian discovered that tumors and normal tissue can be distinguished in vivo by nuclear magnetic resonance (NMR) because of their prolonged relaxation times, both T1 (spin-lattice relaxation) or T2 (spin-spin relaxation). Damadian was the first to perform a full body scan of a human being in 1977 to diagnose cancer. Damadian invented an apparatus and method to use NMR safely and accurately to scan the human body, a method now well known as magnetic resonance imaging (MRI).

Damadian has received several prizes. In 2001, the Lemelson-MIT Prize Program bestowed its $100,000 Lifetime Achievement Award on Damadian as "the man who invented the MRI scanner." He went on to collaborate with Wilson Greatbach, one early developer of the implantable pacemaker, to develop an MRI-compatible pacemaker. The Franklin Institute in Philadelphia gave its recognition of Damadian's work on MRI with the Bower Award in Business Leadership. He was also named Knights of Vartan 2003 "Man of the Year". He received a National Medal of Technology in 1988 and was inducted in the National Inventors Hall of Fame in 1989.

Paul Lauterbur - First Nuclear Magnetic Resonance Image - 1973 - ISNE Gold Medal

Paul Lauterbur at Stony Brook University expanded on Carr's technique and developed a way to generate the first MRI images, in 2D and 3D, using gradients. In 1973, Lauterbur published the first nuclear magnetic resonance image and the first cross-sectional image of a living mouse in January 1974. In the late 1970s, Peter Mansfield, a physicist and professor at the University of Nottingham, England, developed the echo-planar imaging (EPI) technique that would lead to scans taking seconds rather than hours and produce clearer images than Lauterbur had. Damadian, along with Larry Minkoff and Michael Goldsmith, obtained an image of a tumor in the thorax of a mouse in 1976. They also performed the first MRI body scan of a human being on July 3, 1977, studies they published in 1977. In 1979, Richard S. Likes filed a patent on k-space U.S. Patent 4,307,343.

Reflecting the fundamental importance and applicability of MRI in medicine, Paul Lauterbur of the University of Illinois at Urbana–Champaign and Sir Peter Mansfield of the University of Nottingham were awarded the 2003 Nobel Prize in Physiology or Medicine for their "discoveries concerning magnetic resonance imaging". The Nobel citation acknowledged Lauterbur's insight of using magnetic field gradients to determine spatial localization, a discovery that allowed rapid acquisition of 2D images. Mansfield was credited with introducing the mathematical formalism and developing techniques for efficient gradient utilization and fast imaging. The research that won the prize was done almost 30 years before while Paul Lauterbur was a professor in the Department of Chemistry at Stony Brook University in New York.

Sir Peter Mansfield - Slice Selection for MRI - ISNE Gold Medal

Mansfield is credited with inventing 'slice selection' for MRI and understanding how the radio signals from MRI can be mathematically analysed, making interpretation of the signals into a useful image a possibility. He is also credited with discovering how fast imaging could be possible by developing the MRI protocol called echo-planar imaging. Echo-planar imaging allows T2* weighted images to be collected many times faster than previously possible. It also has made functional magnetic resonance imaging (fMRI) feasible. It was not until the 1970s with Paul Lauterbur's and Mansfield's developments that NMR at University of Illinois at Urbana–Champaign could be used to produce images of the body.

Ayush Alag - Noninvasive Innovation Medal

Young Inventor Designs Noninvasive Allergy Screen Using Genetics and Machine Learning


From Smithsonian Magazine

One of Ayush Alag’s earliest memories is of biting into a chocolate bar with cashew nuts and suddenly feeling his throat get itchy.

For most of his childhood, the Santa Clara, California resident avoided eating anything with cashews and other nuts that caused irritation as best as he could. By his middle school years, he and his parents wanted to know for sure: did he have a serious food allergy, like 32 million other Americans, or was it just a food sensitivity? They sought the help of an allergist, Joseph Hernandez of Stanford University.

Hernandez told them that the difference between an allergy and a food sensitivity is huge. In the case of food sensitivity, a person can slowly introduce the reaction-triggering food back into their diet little by little to build immunity. If you’re allergic, however, doing so could result in death.

Hernandez recommended that Alag first take a blood test and a skin test, both typical measures in determining allergies, but those results were inconclusive, which was frustrating for Alag when he knew that eating certain foods made him ill. Blood and skin tests are hyper-sensitive and produce false positives nearly 50 to 60 percent of the time, according to the nonprofit Food Allergy Research & Education based in McLean, Virginia. The only way to truly know whether or not he was allergic was to do an oral food challenge, an experience that can be a stressful and occasionally traumatizing for the patient. During an oral food challenge, the patient eats three small amounts of the suspected allergen over the course of an hour under the supervision of a doctor and nurse. Then the patient is observed for four hours following the last dose to see if symptoms occur.

Not only is the process time-consuming for a medical provider, it is also risky, especially for children. If a severe reaction occurs, the child will need to be transported to an emergency room as soon as possible. Food allergies affect approximately eight percent of children, and in decades of oral food challenges being an industry standard there has been just one reported fatality. In 2017, a three-year-old died during a routine challenge, startling the allergy research community.

Thankfully, Alag learned that he did not have a serious allergy after his oral food challenge, but rather a simple food sensitivity, and he was able to make a plan to reintroduce food that used to cause him irritation back into his diet. Now, he says, he can even order cashew Pad Thai without any trouble at all.

“As someone who has been through this whole process and knows what a life changing difference it can be to correctly be classified as sensitized and not allergic, it motivated me to research if there is a way that I can diagnose food allergies that is both safe and accurate,” Alag explains.

Alag presents his DNA test for food allergies at the Regeneron Science Talent Search. (Chris Ayers Photography/Society for Science & the Public)

After his experience, Alag, then 14, decided to look for solutions on his own. At the time, he had been learning about algorithms in school. At home, he was reading previous studies that identified specific genes associated with certain allergies. Driven by his interest in computer science, he designed an algorithm that successfully flags genetic markers linked to food allergies using publicly available data sets. (He focused on 18 genetic markers that were relevant to what he wanted to achieve with allergy testing.) In theory, all you’d need to do is give a blood sample and his test would indicate whether you have allergies to a certain substance or not. Genetic testing is the general direction the field is headed, but the major obstacle that stands in the way is a need for a bigger sample size.

Now, Alag runs his own company called Allergezy. (His childhood allergist, Hernandez, is now a clinical partner with Allergezy.) He is also a top 40 finalist for the Regeneron Science Talent Search for high school seniors, which concludes tonight with a gala, where winners will be announced at the National Building Museum in Washington, D.C. Regeneron will distribute a total of $1.8 million with a top prize of $250,000 for the first place award, according to the Regeneron website.

“These kids are working on projects that could truly change lives around the world. In Ayush’s case, he could help improve diagnosis for the increasing number of people suffering from food allergies,” says George Yancopoulos, president and chief scientific officer of Regeneron (who was also once a finalist in the competition), in a statement via email.

Alag’s technology is far from market-ready; it still needs a lot of refining, which will require sequencing more DNA samples, and testing to prove that it is reliable and accurate. Allergezy recently received a $10,000 grant from the Silicon Valley genetic research startup Illumina to expand the datasets, obtain more blood samples and do more genetic sequencing. (All of that and much more needs to happen before they approach the FDA approval process.) He is one of nine Regeneron finalists who have applied for a patent, notes Maya Ajmera, president and CEO of the Society for Science & the Public, in a statement via email.

“Ayush’s machine-learning algorithm, which can safely diagnose a food allergy from a patient’s blood profile, has the potential to make a real impact on people’s lives,” says Ajmera.

And that’s exactly what Alag hopes to do some day. He explains how much of a relief it is for him not to live with the constant fear that he might have a reaction to the food in front of him, and he just wants others to feel that same sense of freedom.

“It’s a lot easier now for me and my entire family, and it’s a much better lifestyle change,” Alag says.