What do Marie Curié's original "blue ray", high-speed cosmic rays from distant stars penetrating our bodies every second, and the study of an organism's metabolic processes have in common?
In this article, we continue our discussion on the evolution of medical products, with focus on diagnostic imaging and PET technology. We will explore the history and advancements of this area of medical technology, current status, implications within our global society, and future outlook. Come with us and explore the story of PET and how we arrived from 1911, with a gram of glow-in-the-dark "Blue Ray" found after studying 4 tons of rock, to the PET or laptop-sized solid-state Gamma Cameras of today. |
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Some basic concepts.
What is PET? PET is an invasive technique in which a radiopharmaceutical that generates radiation from inside the body is injected, ingested or inhaled. This radiation is detected by a ring-shaped scanner around the body and transformed into an image. It is a functional imaging technique: this is due to its rationale, as it is based on detecting how and where a metabolic process is occurring, unlike other imaging studies which are mostly structural.
How is this radiation generated? By particle annihilation. When a proton passes through matter, after dispersing its kinetic energy, it encounters an electron. Both interact and are annihilated, emitting the rest of their energy in the form of two gamma ray photons (also explained by Einstein's theory E=mc2). The distance the proton or positron travels before this happens depends on its own energy, and is what limits the spatial resolution of the PET image from 1 to 2 mm. These two gamma rays exit in opposite directions and their simultaneous detection allows a more precise localization of the isotype than in SPECT. Photons are these individual light beams and are the smallest and sharpest indivisible units of gamma rays.
How are these photons made visible? Scintillation detectors use crystals. Each gamma ray entering a crystal creates a very small flash of light. This scintillation is transformed to an electrical pulse by a photomultiplier tube. The height and amplitude of this generated pulse is proportional to the Gamma ray energy, and inversely proportional to the wavelength of the incident photon. The count of detected photons represents the amount of radioactive tracer: i.e. it gives a quantitative indicator of the activity or metabolism of the tissue under study.
What are tracer kinetics? A biomedical compound is labeled with a radioactive isotope and a tracer is generated. In nuclear medicine studies, the trajectory and evolution of this tracer is followed, reflecting biochemical functioning. There is very little interference with normal physiology.
Why has this technique had so much use and success in oncology: because of the kinetics of the tracers. Because the cells of neoplastic tissues have a high glycogen metabolism. Fluorine-18 is used, which binds easily to 2-deoxy-D-glucose, and the tracer Fluorodeoxyglucose 18FDG is obtained. When distributed in the body (inhaled, ingested or administered intravenously), and as neoplastic cells consume more glucose than adjacent tissue cells, they will be more marked with Fluor-18.
Let's walk through some of the highlights of PET's history together.
Like the pieces of a perfectly arranged domino succumbing to the inescapable force of gravity, the milestones in this story, glimpsed and studied by restless and brilliant minds, kept nudging each other in a precise and perfect order. Delayed at some point probably by ignorance and prejudice. These are some of the most outstanding pieces of this domino:
These are some of the most outstanding pieces of this domino:
July 13, 1898. Pushed by the hand of the first woman Nobel Prize winner, and the first person to win two of them (Physics and Chemistry): Marie Curie, the first piece falls: the discovery of Radioactivity. The scientist, together with her husband, wrote in her notebook: Polonium. Element that they identified and named after its origin.
December 21, 1898. The second piece: the isolation of the "ray". Also pushed by the Curie husband and wife, who announced the name of a new element identified by them: Radium (Ra), which means lightning in Latin.
1911. The third piece: The 10 tons of rock from Austria: Curie and André Debierne were able to isolate radium (Ra) in metallic form. After the Curie husband and wife had been treating for 4 years about 10 tons of rock from a mine in Austria, they obtained 1 mg of this element. The samples glowed pale blue in the dark.
1930 The fourth piece was pushed by Ernest Lawrence who conceived the idea of the Cyclotron: it is a type of particle accelerator where radioisotopes (currently used in medicine) are manufactured. This device propels a beam of protons in a circular trajectory that bombards stable isotopes. They could then identify and produce a large number of radioisotopes: Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18, among others. Lawrence's working group unknowingly produced Cobalt, Copper and other radioactive elements by bombarding the metallic elements of their cyclotron.
1932 The fifth piece: protons. First postulated theoretically by Physicist Dirac, and then experimentally by Physicist Anderson, who observed experimentally that cosmic rays had particles with the mass of an electron moving in a strong magnetic field along a path, indicating that they had a positive charge: protons (positive electrons).
1934 The sixth piece is pushed again by Curie and Joliot who made the first demonstration that radioactive atoms could be produced artificially.
From "lightning" to imaging.
1948 The seventh piece is the first approach to imaging: measurement of cerebral blood flow. Kety and Schmidt used non-radioactive tracers using the Fick Principle to measure it. This principle states that blood flow to an organ can be calculated using a tracer, knowing the amount of tracer substance absorbed by the organ per unit time, and the concentration of tracer substance in the arterial blood supplying this organ.
1950 The eighth piece: the rectilinear scanner. Benedict Cassen introduced imaging to nuclear medicine with his rectilinear scanner.
Hal Anger develops the "well counter," a device capable of measuring small quantities of radioactive substances.
1952 The ninth piece: Hal Anger. Both Curie and Anger were not only driving pieces, but were pieces of this domino themselves. The scientist had already been working for years as an assistant in the laboratory of J. Lawrence and Cornelius Tobias. He completed his first Gamma Camera prototype in this year. Although this equipment had a low sensitivity, as well as long exposure times, requiring an hour or more. But as a great advantage of its predecessor the rectilinear scanner, it could capture the image of an entire organ.
1956 The tenth piece, once again by Anger. He finished refining the Camera he had previously invented by using photomultiplier tubes to know exactly where the flash of light occurred, thus quickly generating an image of the distribution of the tracer in the body, i.e. detecting positrons. This facilitated the study of dynamic functions. Today nuclear medicine has medical imaging devices that can study with high resolution the bones, kidneys, heart, brain, liver. And the latest gamma cameras do not differ substantially from Anger's original. Scintillation camera, Scintillation camera.
1959 Eleventh piece. Anger developed the principle of coincidence detection and the first positron camera.
Donald Van Dyke, a research physiologist, was a pioneer in using the positron camera to demonstrate blood flow and marrow distribution in various disease states.
Chemist Yukio Yano fabricated the 32-Fe and 18-F isotopes, which in conjunction with the positron detection chamber facilitated the study of blood disorders as better visualization of Fe distribution and kinetics could be obtained.
1966 Twelfth piece: The Multiplane Tomographic Scanner. Anger develops the first of this equipment, which makes it possible to visualize with a high level of detail the tissues and organs of the body using X-rays. Anger is a scientist with more than 15 U.S. patents. Anger received more than 13 awards and honors, including the John Scott Award in 1964 for the development of the positron camera; Guggenheim Fellowship, 1966; Gesellschaft fur Medizin Award, 1971; honorary doctorate in science, Ohio State University, 1972; Nuclear Medicine Pioneer Citation, SNM, 1974, among others.
1974 Thirteenth item: The first Positron Emission Tomography equipment is commercialized.
1991 Fourteenth piece: Clinical PET: "It's time has come": It was the cover of "The Journal of Nuclear Medicine", referring to the fact that it had taken a long time for PET to reach the level of clinical applications, but with an assured future given its advantages of detection and localization of metabolic functioning in the living human body.
The path of the pieces begins to branch out, and the pieces to evolve.
At the end of this decade it was found that, using PET in conjunction with CT, greater anatomical accuracy of structures could be obtained.
Today some advances include the solid state Gamma Camera with the size of a Laptop, approved by the FDA in May 1997. Solid state detectors are used instead of crystals and photomultiplier tubes.
Uses
Dual modality PET/CT or PET/MRI, which combines functional and anatomical diagnostics, are the innovation in nuclear medicine. Its application in oncology facilitates the anatomical localization of tumors of the head, neck, abdomen and pelvis, with better interpretation and localization specificity in the images.
Basically because the advantages of each equipment are enhanced, minimizing the disadvantages they have separately: this is detecting the increased glucose metabolism, added to the structural specificity. It was found that, if performed in separate equipment, the images could be reliable in more static organs such as the brain, but in other more mobile organs or those that can undergo distension such as the liver, spleen, lungs, the structural specificity drops notably.
The use of the dual system has the following advantages:
The planning of intensity-modulated radiation therapy.
Monitoring and evaluation of treatment effectiveness.
Detection of recurrences.
Staging phases
Targeted biopsy.
Planning surgeries in complex anatomical areas such as the head, neck and pelvis region.
Differentiate between physiological and pathological uptakes.
Uses in Neurology.
With PET/CT brain processes are evaluated with Beta amyloid, and is a relatively new tool and extremely helpful for neuronal diseases such as:
Parkinson's and Alzheimer's when symptoms are mild in order to slow them down.
Also for the differential and early diagnosis of dementias.
Localization of epileptic foci in refractory epilepsies as a preventive method.
Study and assessment of other psychiatric diseases.
Assessment of the degree of malignancy of a brain tumor.
Uses en cardiology.
Myocardial perfusion at rest or stress is used to monitor therapeutic interventions, detect myocardial ischemia, and evaluate prognoses in patients with known myocardial disease. These studies are comparatively shorter in duration and more sensitive than others such as SPECT. It allows quantification of myocardial flow in ml/minute/per gram of tissue at rest and under stress. It is also possible to determine the presence of viable cardiac muscle in patients who have had myocardial infarction, distinguishing living muscle from necrotic muscle.
How does radiation from imaging studies affect us, and does it increase our risk of cancer? Will we have a higher risk of cancer because of this?
It is well known that radiation is harmful to health. According to Cancer.net and Cancer.org, the risks of potentially increased cancer risk due to radiation exposure from PET/CT/XR are minimal and difficult to quantify. For children and some individuals in particular this risk may be slightly higher as they are more sensitive to radiation, and should be protected from radiation as much as possible. Depending on multiple factors such as: age, body weight and size, sex, type of study, area of the body exposed, among others. In general and for a person of average adult age, the balance is that the benefits of the diagnosis are greater than the risks of exposure to its radiation.
We should not lose sight of the fact that these studies are indicated under the consideration of a physician or a team of physicians, who evaluate this risk-benefit, in the context of a multiplicity of factors, and taking into account that radiation will accumulate throughout life.
Regarding these issues, information of interest can be found at www.imagewisely.org and www.imagegently.org.
Conclusion
Undoubtedly, when the genius of brilliant minds is used for the purpose of helping others, and, with the eagerness to discover new paths, previously unthinkable destinations are reached. Being able to make an accurate diagnosis in pathologies from early stages such as cancer, Alzheimer's, or myocardial perfusion, among others ... has been undoubtedly some of the most awaited by humanity both on the side of patients and medical professionals. Recent applications in Neurology and Cardiology have also shown that new pieces of this domino can be expected in other specialties and with new pathologies to be diagnosed.
I will end with a quote from Marie Curie: "Life is not easy for any of us. We must have perseverance and, above all, self-confidence. We must believe that we are gifted for something and that this must be achieved."
About the Author:
Maria Soledad Gomez has 10+ years of industry experience working in a variety of roles within regulated industry, healthcare and medicine, including food/beverage, hospitals and veterinary medicine. Maria Sole writes technical articles on a wide variety of topics in the medical field.
About the Editor:
Brian Hoy has 20+ years of industry experience in medical devices and business formation, covering the complete life cycle with global scope. Brian consults for industry and gives general advisory and off-hours support. (English translation by Brian Hoy)
Publication ID: PUB0007EN
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