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milestones from the archives

LEARNING TO SEE INSIDE THE BODY

Originally published Aug 2021

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Learning to See Inside the Body

BY Connie Mitchell

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William Röntgen produced the first X-ray of a human body in 1895.. Photo courtesy of Science Photo Library

The very first X-ray image is a blurry, ghostlike view of a woman’s left hand, two sizable wedding rings visible on her third finger. Using his wife as his test subject, German physicist Wilhelm Röntgen used the power of the X-ray to gaze at bones beneath his wife’s skin, something he couldn’t have done before without an incision. Six years later, Röntgen won the 1901 Nobel Prize in Physics. The practice of medicine had changed forever.

The early years

In 1896, just a month after the first X-ray became public, Charles Curtman, an analytical chemist at the Mallinckrodt Chemical Co. and instructor at Missouri Medical College, the predecessor to Washington University School of Medicine, delivered a lecture about the new technology to a packed auditorium of physicians, chemists and alumni. Clearly, the medical world was sitting up and taking notice of Rontgen’s wondrous new discovery.

The following year, the British Institute of Radiology was established, now the oldest radiological society in the world. Physicians with access to the new technology looked at fuzzy images developed on glass plates until film was introduced in 1918. During the early 20th century, the new ability to image bones was called roentgenology, in homage to Röntgen. Academic medical centers began to create roentgenology departments, and even in the earliest days of this nascent field of medicine, physicians and scientists began to explore the possibilities for using X-rays in treatment as well as diagnosis.

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The first successful cholecystogram of the human gallbladder was produced in 1924.
Photo courtesy of Washington University School of Medicine Bernard Becker Medical Library

Some of those researchers were working at Washington University’s Medical Department in the 1920s and began experimenting with X-ray images of the gallbladder. Known as cholecystography, the technique involved injecting radioactive dye that was visible by X-ray; it was among the earliest efforts in what would become the field of nuclear medicine.

Mallinckrodt Chemical Co. began manufacturing radiology contrast agents and established a collaborative relationship with the university.

Around the same time, St. Louis’ Jewish Hospital (now Barnes-Jewish Hospital) hired its first full-time radiologist, Paul Schnoebelen. Physicians were beginning to specialize in the new field, and researchers were exploring ways to improve on Röntgen’s original technology, which relied on cathode ray tubes.

Nationally, hospitals and medical schools were beginning to define radiology as a separate medical specialty; in 1927, Washington University established its Department of Radiology, moving radiologists into their own domain instead of including them in the surgical department. Having shed the cumbersome “roentgenology,” the field became known as radiology. In 1929, the American Medical Association created standards for radiology departments, and specialists began seeking board certification in 1933.

Around that time, planning began for a radiology institute affiliated with Washington University. Nationally known surgeon Evarts Graham proposed the institute to his faculty colleagues, suggesting it focus on four areas: diagnostic services, radiation therapy, teaching and research.

In 1931, after several years of fundraising and planning, Mallinckrodt Institute of Radiology opened with major funding from the General Education Board and Mallinckrodt Chemical Co.

Mid-20th century advances

Early forays into treatment with X-rays and radioactive compounds proved illuminating—but also presented an element of danger for patients and physicians alike. A memorial, erected in 1936, still stands on the grounds of St. George’s Hospital in Hamburg, honoring the “X-ray martyrs” of these inaugural attempts to treat disease with radiation.

As scientists worked to understand the possibilities, effects and limits of radiation in diagnosis and treatment, the field was poised to leap forward when physicist Ernest Lawrence used his new invention, the cyclotron, to create phosphorus-32, a nuclear isotope that was injected into a 28-year-old patient with leukemia to destroy the cancer. The treatment may have killed cancer cells, but it also affected healthy cells. Nevertheless, the work was foundational to using radiologic compounds for therapeutic purposes.

In 1946, the Journal of the American Medical Association published an article documenting the successful use of radioactive iodine to treat a person with advanced thyroid cancer. Within a few years, radionuclides were increasingly common therapeutic agents, and nuclear medicine became its own board specialty in 1972. Mallinckrodt Institute of Radiology began operating its own dedicated cyclotron in 1964, the first one in the nation to be housed on a medical campus.

The early 1960s also saw the advent of commercial medical ultrasound imaging, allowing physicians to visualize 2D images created by bouncing sound waves off matter. Mallinckrodt installed its first ultrasound machine in 1973, sharing the device with the cardiology department.

In yet another major advance, magnetic resonance imaging, or MRI, joined the array of medical imaging technologies in 1977. As the name implies, this modality uses a strong magnetic field and radio wave frequency to create images based on the movement of protons within the body. Like ultrasound, MRI offers radiologists a non-radiation-based imaging option, although the magnetic forces used during the scan make it dangerous for people who have implanted pacemakers, metal clips or valves.

Mallinckrodt’s first MRI unit arrived in 1983. The $1.5 million machine with a 12,000-pound magnet required construction of a physical addition to the fifth floor of the institute’s building.

An explosion of technology

About 85 years after Röntgen’s discovery, Richard Wahl, MD, was fresh out of medical school and excited about the newest possibilities in medical imaging. “I’ve been at it a long time,” muses Wahl, who now serves as director of Mallinckrodt and chair of radiology at Barnes-Jewish Hospital.

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CT scanner control room, circa 1975. . Photo courtesy of Washington University School of Medicine Bernard Becker Medical Library

“I remember how transformative CT scanning was when I was just entering the field,” he says. Invented by Godfrey Hounsfield and Allan Cormack in 1972, the first computed tomography (CT) scan was capable of imaging organs and soft tissues.

“We were moving from 2D to 3D images, and Mallinckrodt was one of the first places in the nation to acquire equipment that created CT scans of the head, displaying the brain in three dimensions. I was aware of this progress; it was a very exciting time.”

The young Wahl’s interest was piqued by the ability to visualize the brain as a fully formed model that could be examined from various angles. Aware that Mallinckrodt had recently acquired one of the nation’s first full-body CT scanners, in 1979 Wahl entered a radiology residency at Washington University School of Medicine, anticipating his use of the new technology.

The significant move from 2D to 3D imaging occurred only about 10 years before Wahl began his residency. Röntgen’s original discovery of X-rays relied on radiations of light or radio waves passing through objects from a fixed cathode ray tube. Solid objects appear as white outlines in subsequent images. CT works on the same principle, but instead of sending X-rays from a fixed source, the patient lies on a bed inside a circular aperture, known as a gantry, while the CT’s X-ray source moves around the body to created cross-sectional image “slices” that can then be digitally combined into a 3D image.

“Imaging of cross-sectional anatomy really moved us forward in using radiology for diagnosis of a wide range of conditions,” Wahl says. That ability formed the basis for modern radiology, a broad field relied upon by almost every medical specialty for diagnostic and, increasingly, treatment modalities.

Wahl’s interest in CT scanning as a new frontier was soon augmented by additional 3D imaging technologies. Mallinckrodt, already known as a national leader in radiologic research and practice, earned a permanent place in the history of radiology when the first positron emission tomography (PET) machine was developed at Washington University School of Medicine by Michel Ter-Pogossian, a physicist and professor of radiology; Michael Phelps, a nuclear chemist and junior faculty member; and Jerome Cox, founder of the medical school’s Biomedical Computer Laboratory.

Now one of the field’s primary imaging modalities, PET produces images of metabolic functions. Using radioactive tracers, radiologists can see how organs and tissues are functioning. PET scans can measure blood flow, oxygen use, blood sugar metabolism and much more.

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A team of Mallinckrodt scientists, physicians and clinicians developed the first positron emission tomography (PET) machine; photo circa 1980. . Photo courtesy of Washington University School of Medicine Bernard Becker Medical Library

The initial trio of PET developers at Mallinckrodt formed the nexus of what became a team of almost 20 researchers and clinicians. Phelps and other scientists authored the first scholarly articles on PET in 1975. Phelps later moved to UCLA, where he was involved in creating the first commercial PET systems.

“The development of PET tracers has been an area of strength and active research at Mallinckrodt for many years,” Wahl says, adding that one such example is radioactive agents developed at the institute and recently approved for breast cancer imaging by the Food and Drug Administration (FDA).

Dmitry Beyder was a kid when Wahl was first learning how to use and interpret CT, PET and other imaging technologies. But as a young nuclear medicine technologist—educated in how to administer radioactive contrast agents and then operate the sophisticated imaging equipment—he knew Mallinckrodt as the “birthplace of the PET scan” and jumped at the chance to supervise its nuclear medicine and PET departments six years ago.

“I love the science and the medicine, and wanted to be part of it,” Beyder says. “The doctors I worked with when I came to the institute are the same ones who literally wrote the textbooks I studied in college.”

Beyder, now serving as a program manager supervising CT, nuclear medicine/PET and patient transport operations at Mallinckrodt, oversees about 200 people who perform about 130,000 CT scans and 10,000 nuclear medicine scans per year, making the institute one of the busiest radiology facilities in the nation.

He works closely with Laurie Oberholtzer, interim director of radiology and transport services, and program manager for MRI and ultrasound. Oberholtzer’s career spans more than 30 years, during which, like Wahl, she’s marveled at the advances in radiologic technology. “When I started working as a young radiographer, it took 25 minutes to perform a CT scan of the chest, abdomen and pelvis, format it and print the images on film,” she says. “These days, it takes less than a minute to complete the entire scan, reconstruct the images and send the data to the radiologist for review.”

In today’s world, managing images is similar to sending a text. You select your destination and hit send. “Technology continues to advance, with the patient and end user as the priority for development.” Oberholtzer says.

As the speed of radiologic technology increased, so did patient volume. Now, physicians rely on radiology for both diagnostic information and treatments for everything from identifying pneumonia to musculoskeletal conditions to cancer.

“Despite everything available to us, the chest X-ray is still the most common medical imaging order we receive,” Oberholtzer says. “The pandemic certainly had an impact on that. Barnes-Jewish Hospital treated many patients with COVID-19 who arrived at the emergency department and had a chest X-ray.”

Since its founding 90 years ago, Mallinckrodt has grown to a more than 400,000-square-foot facility. The 13-story main building is augmented by satellite facilities at Barnes-Jewish Hospital and St. Louis Children’s Hospital, as well as imaging centers and services provided throughout St. Louis and St. Charles counties, as well as other locations.

“We are a very, very collaborative organization,” Oberholtzer says. “What we do touches virtually every single type of medical specialty.” And to work with all those specialties and stay up-to-date on the rapidly evolving technologies, she says that radiologists and technologists have to be like chameleons. “We’re on the forefront of technology, so we’re always learning, changing practice because things are developing so quickly. We want to offer our patients and providers the best imaging available. It’s who we are and what we do to remain leaders in the field.”

The future Is bright

Oberholtzer’s chameleon metaphor is apt as Mallinckrodt continues to acquire among the newest technologies for state-of-the-art radiology service. A recent example is the addition of six new Force Scanners: lightning-fast CT machines that allow patients to spend less time on the table and receive less radiation while creating crystal-clear, full-color images that are available for almost instantaneous assessment. Beyder compares it to having “a garage full of Lamborghinis.”

Today’s technologists and radiologists are on the cusp, yet again, of an exciting new era of medical treatment: theranostics. Scientists are finding new ways to concurrently target and treat malignancies and other disease-causing molecules with ever more sensitive and specific nuclear imaging abilities. Radiochemists work behind the scenes to identify molecular compounds that will carry therapeutic agents directly to cancer cells, leaving healthy cells intact.

“We’re really building on advances in computing and artificial intelligence, or AI, to interpret images very consistently and efficiently,” Wahl says. In affiliation with White Rabbit AI, a California-based technology firm, Washington University scientists recently built an algorithm that helps radiologists better determine the need for follow-up diagnostics based on mammogram images. The software was approved by the FDA and is one example of how AI is being integrated into radiologic technologies.

No matter how advanced the systems get, however, Wahl says radiologists will always be needed to make final determinations of increasingly refined information. In fact, with the dawn of theranostics and other types of interventional radiology, radiologists are no longer the unseen doctors sitting in dark rooms looking at X-rays. Patients increasingly interact with radiologists and technologists during diagnostic and treatment appointments.

Wahl is as excited about the field now as he was in 1979, and Mallinckrodt Institute of Radiology is poised to continue its tradition of education, research and service to the community, seeking new ways to view and treat the body from the outside in


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