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29 Aug 2024
Cancer Treatment, Nuclear Medicine Versant Physics 0 comment

Celebrating the Achievements of Dr. Darrell R. Fisher:  A Journey of Scientific Excellence

Earlier this year, the Columbia Chapter of Health Physics Society and the Georgian Health Physics Association nominated Dr. Darrell R. Fisher for the 2024 Distinguished Scientific Achievement Award of the Health Physics Society (HPS). Fisher is a nuclear medicine physicist with Versant Medical Physics and Radiation Safety. He received the Distinguished Scientific Achievement Award in July 2024, during the 16th International Congress of the International Radiation Protection Association and 69th HPS Annual Meeting in Orlando, Florida. The award recognized Dr. Fisher’s scientific contributions over a career spanning more than five decades in applied radiation safety sciences, including internal dosimetry, radiobiology, radiochemistry, and design and testing of radiopharmaceuticals and medical devices. His innovative research has led to numerous significant advancements in the applied radiation health sciences. 

Discoveries in Chelation Therapy and Radiotoxicity

One of Dr. Fisher’s early discoveries was identifying the toxicity and congenital birth defect teratogenicity of the heavy-metal chelating agent CaNa3DTPA compared to the non-toxic ZnNa3DTPA. This research showed the importance of maintaining cellular zinc and manganese availability during critical growth periods to ensure uninterrupted cell division.  His work was instrumental in enhancing the safety and effectiveness of emergency decorporation therapy for nuclear workers accidentally exposed to plutonium, neptunium, and americium. By establishing the safety of ZnNa3DTPA, Dr. Fisher’s work paved the way for safe and effective treatments after actinide contamination events, significantly impacting emergency response protocols and worker safety in nuclear industry.

Advances in Applied Microdosimetry

Dr. Fisher performed the first microdosimetry calculations for plutonium-238 and plutonium-239 in beagle dog lung tissue specimens. His research disproved the “hot particle hypothesis” claimed by Thomas Cochran and Arthur Tamplin; Fisher showed that their hypothesis could not be supported by dosimetry or radiobiology.  Fisher described the fundamental science underlying relative biological effectiveness (RBE) relationships between alpha-particle dose and two critical biological endpoints: cellular mutation and primary DNA damage. This work demonstrated that varying the specific activity and spatial geometry of plutonium microsphere sources could result in vastly different biological outcomes at constant absorbed dose. These findings were pivotal to better understanding radiation effects at the microscopic level, influencing safety standards, and advancing what would later become new cancer treatment approaches with alpha-emitting radionuclides.

Innovations in Cancer Treatment

Dr. Fisher was an early proponent of short-lived alpha emitters such as radium-223 and actinium-225 for cancer treatment. He performed the first cellular-level microdosimetry calculations for alpha-emitter-radiolabeled monoclonal antibodies used in cell-targeted radioimmunotherapy. His pioneering work in developing treatment-planning dosimetry for clinical radioimmunotherapy supported the high-dose treatment of relapsed lymphoma, leukemia, and multiple myeloma patients.  In the laboratory, he helped to develop and test several innovative alpha-emitter complexing agents, including macrocyclic cages and nanoparticle delivery constructs for next-generation therapies.

Contributions to Uranium Toxicology

Dr. Fisher’s assessments of dosimetry and health effects from uranium intakes led to a modified biokinetic model for inhaled uranium hexafluoride compounds. His research provided crucial insights following the Sequoyah Fuels accident in Oklahoma, where workers were exposed to uranium hexafluoride. Dr. Fisher’s model improved the understanding of uranium’s behavior in the body, leading to better understanding of uranium toxicity. 

Pioneering Work in Radionuclide-Polymer Composites

Dr. Fisher conceived, designed, patented, and tested novel radionuclide-polymer composites employing insoluble crystalline yttrium-90-phosphate microspheres administered in a thermo-reversible hydrogel delivery matrix. This innovation has enabled direct interstitial therapy of nonresectable solid tumors, providing new avenues for cancer treatment in both humans and veterinary animals.  Precision radionuclide therapy by direct intra-tumoral injection maximizes therapeutic ratios, a key measure of treatment safety and efficacy.  His work has enabled highly efficient delivery of radiation to tumors, minimizing damage to surrounding healthy organs and tissues and associated side-effects of radiation therapy.

Enhancing Patient Safety in Nuclear Medicine

Dr. Fisher helped develop and published practical methods for patient-specific dosimetry to characterize the severity of inadvertent radiopharmaceutical extravasations in diagnostic and therapeutic nuclear medicine.  Fisher has specialized in medical internal radiation dosimetry, an essential element of managing patient safety and improving therapy outcomes. 

Lifelong Commitment to Radiation Safety

Darrell Fisher’s journey in health physics began in 1973 as an undergraduate research assistant at the University of Utah’s Radiobiology Laboratory. His early research on extracting americium-241 from skeletal surfaces in live mice laid the foundation for his future contributions to radiation safety and radiobiology.  Over the years, his work has led to significant advancements in understanding and mitigating the effects of radiation exposures in medical and occupational settings. His dedication to the field is evident in his continuous efforts to improve safety standards, develop innovative treatment methods, and educate future generations of health physicists.

The 2024 Distinguished Scientific Achievement Award recognizes Dr. Fisher’s commitment to scientific excellence and discovery for work that not only advances scientific knowledge but also improves patient care and radiation safety.  His diverse contributions to the field of applied radiation safety sciences, in collaboration with highly respected research associates and colleagues worldwide, have been impactful. His innovative research, spanning over 50 years, has led to significant advancements in worker safety, dosimetry and microdosimetry, radionuclide therapy treatment planning, direct interstitial treatment of inoperable tumors, and patient safety in nuclear medicine.

Dr. Fisher Headshot, 2024.
18 Dec 2023
Large size motorized 3D water phantom system for dose distribution measurement of radiation therapy beams in real daily routine practice used as a part of quality control of radiation therapy.
Cancer Treatment, Dosimetry, Nuclear Medicine, Radiation Therapy, Uncategorized Versant Physics 0 comment

What’s Inside Matters Most: Internal Dosimetry

Medical physics has been an integral part of medicine and healthcare over the greater part of the last century. Applying physics theory, concepts, and methods, scientists have created patient imaging, measurement, and treatment techniques that revolutionized the medical world. One product of medical physics has been the evolving specialty called radiopharmaceutical dosimetry, the calculation of absorbed dose and optimization of radiation dose delivery in cancer treatment. Today, we address internal dosimetry, the subset of medical physics that aims to optimize treatment and protect the patient from any undesirable side effects.

What is internal dosimetry?

Dosimetry is the measurement of radiation energy imparted to body organs and tissues. Radionuclides emit beneficial ionizing radiation that is useful for both diagnostic imaging of various diseases as well as for cancer treatment. Thus, medical internal dosimetry is the assessment of internal radiation dose from incorporated radionuclides associated with such life-saving radiopharmaceuticals.1 Radiation dose is the amount of energy imparted by radiations emitted during disintegration of radioactive atoms that constitute part of the radiopharmaceutical chemistry. Dose to organs of the body is quantified per unit mass (or weight) irradiated tissue. Dosimetry provides the fundamental quantities needed for several important purposes, including record-keeping, radiation protection decision-making, risk assessment, and cancer-treatment planning.2 The purpose and objective is to optimize medical benefit while minimizing potential radiation damage to body cells, tissues, and organs.

Dosimetry is a complex physical and biological science. Internal dosimetry provides critical information needed to better understand the biological mechanisms governing radionuclide uptake, translocation, and excretion from the body. The radiation dose imparted depends on the type, amount, and distribution of radionuclides, as well as specific nuclear properties, such as energy emitted.

Internal dosimetry differs from “external” dosimetry, which deals with the radiation dose from sources outside the body. Devices such as dosimeters measure external dosimetry directly, while internal dosimetry relies on indirect methods of radioactivity inside the patient using bioassay and imaging measurements.3 Bioassay is the measurement of the activity or concentration of radionuclides in biological samples. Samples can include urine specimens, feces, blood, or breath. Imaging techniques, such as whole-body counters or gamma cameras, can detect the radiation emitted by the radionuclides inside the body. This helps to provide information on their location and quantity.1

When is internal dosimetry used in healthcare?

Internal dosimetry mainly benefits patients who receive radionuclide therapy, a treatment that involves administering radioactively labeled proteins, such as monoclonal antibodies, to target specific types of cancer.3 It also helps to evaluate and account for unique patient variations in biodistribution—the way that different subjects respond to treatment. Internal dose assessments analyze radionuclide behavior in both normal (healthy) organs, as well as tumors. For example, imaging measurements provide physicists with important information to determine tumor uptake, retention, and clearance. In doing so, administered activity can be tailored according to patient health status, age, size, sex, and basal metabolic rates.

How does internal dosimetry produce useful data?

The main challenge of internal dosimetry is to track and follow the uptake, redistribution, metabolism, and clearance of the administered radiopharmaceutical inside the body over extended time periods after administration.4 Tracking sometimes involves mathematical modeling to describe the absorption, distribution, metabolization, and excretion of radionuclides by the body. Biokinetic models may be developed from the study of population groups, knowledge of radionuclide behavior in different organs, and the unique chemistry of each radiopharmaceutical. Biokinetic models incorporate mathematical compartments representing a particular organ or a tissue, and descriptions of the transfer rates that reflect the movement of radionuclides from one body compartment to another.1

Summary

Internal dosimetry is an important tool for radiation protection, especially in the fields of nuclear medicine, occupational health, and environmental monitoring. Dosimetry helps to customize or personalize nuclear medicine in cancer patients. In a broader sense, internal dosimetry is also applied to occupational and environmental health to prevent or reduce the exposure to radionuclides, by providing information on the sources, pathways, and levels of intake, and by suggesting appropriate measures, such as respiratory protection, contamination control, or dose limits. Internal dosimetry can also help to verify the adequacy of workplace controls, to demonstrate regulatory compliance, and to provide medical and legal evidence in case of accidental or intentional exposure.

Special software tools have been developed for the clinical nuclear medicine setting to facilitate medical imaging and calculate internal doses.

QDOSE® Multi-purpose Voxel Dosimetry (Personalized Dosimetry in Molecular Radiotherapy) is a complete, one-stop solution software for all internal dosimetry needs with multiple parallel workflows. With USFDA 510(k) clearance granted in August 2023, QDOSE® has proven its quality and compliance. To learn more, visit our QDOSE® webpage or schedule a meeting with our team.

Sources

  1. Sudprasert W, Belyakov OV, Tashiro S. Biological and internal dosimetry for radiation medicine: current status and future perspectives. J Radiat Res. 2022;63(2):247-254. doi:10.1093/jrr/rrab119
  2. Bartlett R, Bolch W, Brill AB, et al. MIRD Primer 2022: A Complete Guide to Radiopharmaceutical Dosimetry. Society of Nuclear Medicine & Molecular Imaging; 2022.
  3. Chapter 7 External and Internal Dosimetry. Accessed November 15, 2023. https://www.nrc.gov/docs/ML1121/ML11210B523.pdf
  4. What is Internal Dosimetry – Definition. Radiation Dosimetry. Published December 14, 2019. Accessed November 16, 2023. https://www.radiation-dosimetry.org/what-is-internal-dosimetry-definition/

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30 Jun 2023
Diagnostic and Radiation Therapy Examples
Brachytherapy, Cancer Treatment, Diagnostic Physics, Medical Physics, Molecular Imaging, Nuclear Medicine, Radiation Therapy Versant Physics 0 comment

Other Forms of Radiation Therapy and Diagnostic Machines

In our last blog post, we explored the timeline of diagnostic imaging and radiotherapy developed using x-rays. It was the original discovery of x-rays by Röntgen that led to the creation of these medical practices. However, other researchers of the 20th century also invented diagnostic tools and radiation therapy without x-ray involvement at all. We will explore a few of these imaging and radiotherapy machines or procedures in this blog.

Diagnostic Imaging

MRI

One of the most well-known imaging procedures is MRI, which stands for Magnetic Resonance Imaging. Research for MRI began early in the 1970s, but investigation of the magnetic resonance principles started as early as 1945. By happenstance, Felix Bloch, a Swiss physicist working at Stanford, and American physicist, Edward Mills Purcell at Harvard, conducted—nearly simultaneously—an experiment for a new mode of nuclear induction. This led to published papers from both physicists on nuclear magnetic resonance. After publication, both Purcell and Bloch won the 1952 Nobel Prize for this research.1

The process to produce 2D images in an MRI using nuclear magnetic resonance (NMR) was discovered by Paul Lauterbur and Peter Mansfield. Lauterbur published the first nuclear magnetic image in 1973, eventually producing 3D images as well. However, he still had long to go before these images would be practical for application with actual patients. Mansfield continued to expand on Lauterbur’s work, developing the echo-planar imaging technique to improve image quality and scan time in the late 1970s.  By 1977, physician Raymond Damadian created the first full body MRI machine. Through continuous improvements and further research, today’s MRI provides a safe, effective way of capturing images in the brain, portions of the body, the cardiovascular system, and central nervous system. MRIs provide information on size, location, classification, and grade of lesions so as to aid diagnosing stroke, MS, blood supply issues, and any brain damage.2

Ultrasound

Today, ultrasound is most widely known in the OB/GYN field of medicine. Through its invention, however, this diagnostic tool proved its range of utility before becoming a staple in wellness checks during pregnancies. The origin of ultrasonography is often credited to Lazzaro Spallananzi, a physiologist who discovered echolocation throughout 1794 from various experiments involving bats. The principles that serve as a basis for echolocation are also those functioning for medical ultrasound technology today. In 1942, neurologist Karl Dussik first used ultrasonic waves in a diagnostic procedure while attempting to find brain tumors. He later published a report of musculoskeletal ultrasonography in 1958, laying the groundwork for diagnostic musculoskeletal ultrasound.3

Professor Ian Donald from the University of Glasgow was responsible for the development of medical ultrasound in clinical practice. During his research from the late 1950s into the 1960s, there was clinical skepticism about the use of ultrasound. Many doctors felt that manual abdominal and pelvic examinations had proven adequate for medical diagnoses. With his co-workers, Donald performed several studies to show the likelihood of misdiagnoses of a cyst versus a malignant mass. By publishing the findings in 1958, this became a critical point in time for encouraging use of the medical ultrasound. Donald and his colleagues eventually developed an automatic scanner that utilized a full bladder for early pregnancy detection in 1963. This set the path to the now common practice of ultrasounds in the OB/GYN field today.4

PET Scans

Experimental physicist, C.D. Anderson, observed particles from cosmic rays in 1932 that were the same mass as an electron, but which moved in a strong magnetic field along a path opposite to that of an electron indicating a positive charge. He named these particles as “positrons” or positive electrons.

Emission of these positrons was the proof that Irène Joliot-Curie and Frédéric Joliot-Curie used to prove the artificial creation of radioactive elements to win the 1935 Nobel Prize in Chemistry. The creation of these artificial elements was the main focus over the following years due to their significance to military research from the late 1930s until the 1950s. Imaging studies began taking strides as a result of the desire by Louis Sokoloff, an American neuroscientist who hoped to relate mental function to brain function. This encouraged research through the 1950s until the first tomography unit attempt in 1968. This was the turning point in which PET scan development accelerated into the machines we are more familiar with today.5

PET scans can provide imaging through the detection of the gamma ray pairs that are created when a positron annihilates with an electron inside the tissue where the positron emitting isotope has collected. Whereas other diagnostic scans capture the form of an object, PET scans correlate with the metabolic functions of the tissues that uptake the radioactive compound. The compound with the radioactive tracer is typically a form of glucose called FDG (fluorodeoxyglucose), which is used as an energy source by cells and is given to the patient by means of an IV injection. The more rapid the metabolism of the cells in a tissue, as you have with cancer cells, the more uptake of the FDG. This differential uptake is then seen as an enhanced region on a PET scan. 5

Radiation Therapy

Gamma Rays – Gamma Knife (and Cobalt Therapy)

Gamma radiation from radioactive cobalt sources has been harnessed to create an alternative method for producing therapeutic radiation beams. Similar in design to the previously discussed LINAC machines, a Cobalt unit uses a single Co-60 source to produce the radiation beam for treatment. A machine of a fundamentally different design, the Gamma Knife was developed for the treatment of brain tumors. The Gamma Knife is a stereotactic radiosurgery technique that allows for functional neurological surgery. This machine uses anywhere from 192 to 201 C0-60 arrayed in a semi-spherical shield with each source collimated to point their radiation to the same point in space. This type of precision allows for the potential to treat brain tumors and, in turn, pain, movement disorders, and even some behavioral disorders for patients who had not been responsive to other treatment.6

The Gamma Knife was created through the inspirations of Swedish professors Borje Larsson and Larks Leksell in the 1950s. After an investigation using proton beams with stereotactic devices capable of pinpointing targets in the brain, the researchers eventually gave up on that approach due to cost and complexity. Motivated to find an alternative, Larsson and Leksell went on to create a prototype Gamma Knife system in 1967. The prototype unit was a success, used in Sweden for twelve years  and led to a second Gamma Knife in 1975, before other units began appearing globally in the 1980s.6

Proton Therapy

Protons were discovered in the early 1900s. New Zealand physicist Ernest Rutherford’s research during this time led to his discovery of a nuclear reaction that led to the “splitting” of an atom, where he found protons. As a charged particle, the protons have a finite range in matter. The proton’s interaction with matter produces ionization as the proton slows down along its path, losing energy. A peak of deposited dose then occurs at a depth that is proportional to the proton’s original energy.7

The cyclotron, invented by the American physicist Ernest O. Lawrence along with his associates in 1929, proved an efficient way to produce beams of protons. The cyclotron was capable of accelerating protons to high enough energy that, towards the middle of the 20th century, it was suitable for application in cancer treatments.

Dr. Robert Wilson, another American physicist, was the one to spark the idea of proton therapy for battling cancer. He wrote a seminal paper on the functionality of particle beams (comprised of either protons or other heavy-charged particles) and their ability to disperse their energy in the body—the initial release would be small, then exponentially grow when the beam reaches the end of its path for maximum effect against the tumor. Dr. Wilson published the paper in 1946 and received credit to being the inspiration of further research on proton therapy and the continued development of cyclotrons.7

Brachytherapy and Interstitial Therapy

Brachytherapy is an internal radiation therapy technique involving direct placement of radiation inside a patient’s body cavity. This procedure involves small, radioactive source implants that are generally positioned in a body cavity to be near a cancerous tumor. The radioactive material, typically encapsulated within suitable housing material such as titanium, constantly exposes the tumor to a stream of radiation until removal of the radioactivity. These implants will be temporary, and the patient is either hospitalized or kept in a special suite for the duration of the treatment.

Another form of therapy, interstitial therapy (or interstitial brachytherapy), uses sources that are placed directly into the tissue. These may either be temporary or permanent implants of small, encapsulated sources on the order of the size of a rice grain. For treatments with permanent implants, it is safe enough for the patient to go home with a few simple safety guidelines to follow.8

Brachytherapy was first used in 1901 during an attempt to treat lupus. Alexandre Danlos and Paul Bloch completed this treatment with a radioactive sample from Marie Curie. Shortly after, in 1903, Margareth Cleaves used brachytherapy to treat cervical cancer. It became a popular radiotherapy technique to treat breast, cervical, and prostate cancer. As technology advanced along with the use of brachytherapy through the 1900s, imaging-guidance became a valuable asset. More precise dosimetry became possible and allowed for better brachytherapy planning when doctors could use diagnostic modalities such as CTs, MRIs, or ultrasounds. Today, brachytherapy is a more popular treatment for conditions ranging through gynecological, genitourinary, ocular, and head & neck cancers.9

Summary and Conclusion

The 20th century saw tremendous growth and development in diagnostic machinery and radiotherapy. From soundwave technology that gave way to ultrasound, magnetic resonance inspiring MRIs, and the discovery of positrons, medical and non-medical fields can run diagnostic imaging that suits their needs exactly for the most effective information. Radiation therapy research continuously improves the technology and practices used for the wellbeing of patients. Precision instruments such as the Gamma Knife, Cyberknife, and modern LINACs permit for types of treatments that would otherwise be impossible whilst at the same time reducing the side effects associated with external beam therapy. Proton therapy calculations allow for precise travel through the body for maximum effect against cancerous tumors. Brachytherapy provides a treatment option that directly targets tumors without having radiation travel through the body to the target tissue. Modern image guidance ensures source placement exactly where treatment is necessary and that externally directed therapy beams hit their target. As these modalities evolve, we witness the growing reality of safer, more effective diagnoses and cancer treatments within our lifetimes.

The Versant Physics team has experience that covers a range of equipment. This includes dental units, mobile c-arms and Cone-beam CTs, as well as high energy LINACs and even Proton Therapy units and Cyclotrons. To learn more about how our services can help you, contact us to set up a meeting.

Sources

1. NMR Basics | Nuclear Magnetic Resonance Spectroscopy Facility | University of Colorado Boulder. www.colorado.edu. https://www.colorado.edu/lab/nmr/nmr-basics

2. The History of the MRI – DirectMed Parts & Service. https://directmedparts.com/history-of-the-mri/

3. D. Kane and others, A brief history of musculoskeletal ultrasound: ‘From bats and ships to babies and hips’, Rheumatology, Volume 43, Issue 7, July 2004, Pages 931–933, https://doi.org/10.1093/rheumatology/keh004

4. History of Ultrasound – Overview of Sonography History and Discovery. Ultrasoundschoolsinfo.com. Published December 27, 2021. https://www.ultrasoundschoolsinfo.com/history/

5. Henry N. Wagner, A brief history of positron emission tomography (PET), Seminars in Nuclear Medicine, Volume 28, Issue 3, 1998, Pages 213-220, ISSN 0001-2998, https://doi.org/10.1016/S0001-2998(98)80027-

6. History and Technical Overview | Neurosurgery. Neurosurgery. Published 2018. https://med.virginia.edu/neurosurgery/services/gamma-knife/for-physicians/history-and-technical-overview/

7. History of Proton Therapy – NAPT. NAPT. Published 2018. https://www.proton-therapy.org/about/history-of-proton-therapy/

8. Radiation Oncology. Radiation Answers. Accessed May 31, 2023. https://www.radiationanswers.org/radiation-sources-uses/medical-uses/radiation-oncology.html

9. Mayer C, Kumar A. Brachytherapy. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK562190/

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21 Apr 2023
Cancer Treatment, Medical Physics, Nuclear Medicine, Radiation Therapy Versant Physics 0 comment

X-Ray Evolution: An Accident that Revolutionized Healthcare

It is no question that modern diagnostic imaging and radiation therapy machines play large parts in today’s healthcare. But where did x-ray usage begin? Let’s journey through the timeline of when the first x-ray was taken to today and the growth of its technology into some of the most common machines you may see for diagnostic imaging and radiation therapy.

Diagnostic Imaging

1895

Wilhelm Conrad Röntgen, a physicist, became the first person to observe x-rays, and quite accidentally. Röntgen noticed a glow coming from a nearby chemically coated screen while testing whether cathode rays (known today as electron beams) could pass through glass. After examining the rays emanating from the electrons impacting the glass and their unknown nature, Röntgen dubbed them as “X-rays”. He learned that x-rays could penetrate human flesh but less so higher density substances like bone or lead, and that they were photographable.1

Röntgen’s work paved the way for x-rays to become a vital diagnostic tool in medicine. Dentists such as Otto Walkhoff, Frank Harrison, and Walter König helped spark the advancement of dental radiography, publishing their findings on the topic in 1896.2 During the Balkan War in 1897, doctors used the rapidly improving x-ray radiographs to find bullets and broken bones inside patients on the battlefield.1

1900-1950

Fluoroscopy was invented after the discovery of x-rays in 1900. Continuing into the 20th century, x-rays and fluoroscopy became popular on a consumer level without the risk fully understood. There were rising reports of burns or other skin damage after x-ray radiation exposure; Thomas Edison’s assistant, Clarence Dally, even passed away from skin cancer in 1904 after working extensively with x-rays. Regardless, products like shoe-fitting fluoroscopes were popular from the 1930s until the 1950s so customers at shoe stores could see the bones in their feet.1

On a medical level, scientists progressed with inventing the modern x-ray tube, introducing film into radiology, and the first mammography. Reseachers performed further studies to get a better understanding of the genetic effects of x-ray exposure and the damage caused. Using fluoroscopes in shops tapered off starting in the 1950’s, the practice proven more dangerous than beneficial.3

1970s

X-rays began transitioning into digital imaging by the 1970s which helped save time, money, and storage space.4 Godfrey Hounsfield of EMI Laboratories created the first commercially available CT scanner in 1972. He co-invented the technology with physicist Dr. Allan Cormack and both researchers were later on jointly awarded the 1979 Nobel Prize in Physiology and Medicine.

The cross-sectional imaging, or “slices”, from CT scans made diagnosing health issues like heart disease, tumors, internal bleeding, and fractures simpler for doctors while also being easier on the patients. Through the following years, with how effective the CT scanners proved to be improvements on the design were quickly developed.5

1990s

In the early 1990s, developments with x-ray computed tomography came into a new realm of imaging. Newer CT scanners allowed for the X-ray source to scan in a continuous spiral around the body, which gave an image of a whole organ at once instead of individual cross sections.5 This technique is called helical or spiral CT scanning. C-arm machines created by companies such as Philips introduced Rotational Angiography, in which the C-arm takes a series of images around the patient. This generates an almost 3D picture when viewing the images in a loop.6

Diagnostic Imaging of Today

Diagnostic imaging from the 2000s to present day demonstrate enhanced versions of all diagnostic tools from history. Doctors still use general x-rays for determining severity of injury, check disease, and to evaluate treatment. CT scans have continued to develop so that analysis of issues occurring in a patient’s body can be more clearly seen to determine treatment.7 Mammograms have become instrumental in determining early diagnosis of breast cancer; fluoroscopy still helps doctors today determine effect of movement to certain areas of the body–although not to determine if you should buy a pair of shoes.

Within dental care, veterinary work, and even unexpected industries such as manufacturing and mining, diagnostic imaging has proven its worth.

Radiation Therapy

1895 – 1910

The discovery of x-rays also ushered in research on radiation treatment, eventually leading to some of the machines we see in today’s healthcare. Use of x-ray treatments began between 1895 and 1900, generally delivered as singular, large exposures to the necessary areas. Despite the high doses, the treatments proved to be insufficient over the area of exposure for actual treatment of malignancies, appearing to cause extensive damage to normal surrounding tissues instead.8

1911

As damage from radiation to healthy tissues became more widely known as an issue within the medical world, solutions to a more controlled type of treatment came to creation in 1911. Around this time external beam radiotherapy (XRT) and slow, continuous low-dose-rate (LDR) radium treatments were established from the studied principle of fractionation.8 Splitting the total radiation dose into smaller fractions and delivering it over days achieved better management over cancer growth even while reducing adverse effects to non-cancerous areas of the body.

1920 – 1930

The Coolidge tube, initially invented by William D. Coolidge in 1913 as an improvement over the earlier Crookes tube methods to produce x-rays, became the most popular method for x-ray generation during the 1920s. The Crookes tube used a high voltage between an anode and a cathode, depending on the ionization of the gas in the tube for x-ray production. The Coolidge tube introduced a hot cathode that directly produced electrons from its surface allowing for better control of both energy and intensity of the x-rays produced. Coolidge tubes produced x-rays usable for both diagnostic and therapeutic purposes.

1930 – 1950

Development of more refined machinery truly began within the 1930s for radiation therapy. One of the first machines used for superficial therapy was the Grenz Ray machine. Dr. Gustav Bucky (inventor of the first x-ray grid as well in 1913), invented and made this machine in the 1930s for commercial use by German company Siemens Reiniger. The Grenz Ray machine was effective as a treatment for skin cancers (superficial cancers) due to the rays not passing deep into the body.9 Bucky labeled the rays Granz, the German word for border, as their biological effects seemed to be bordering those of UV light and traditional x-rays.

Treatments for delving deeper started seeing further progression by 1937 through development of supervoltage x-ray treatment; this dubbed the time period from 1930 – 1950 as the “Orthovoltage Era”. Supervoltage x-ray tubes had a staggeringly high kilovolt range compared to previous machines (50 kV to 200 kV). These orthovoltage treatment machines provided higher and variable energies to treat deeper tumors.8 Continued advancements in the Orthovoltage Era became the beginning of electron beam therapy.

1950 – 1980

From the rise in supervoltage x-ray treatment and through inspiration from other machines such as the Grenz Ray machine emerged the linear accelerator. Also known as a LINAC, these machines nowadays are large devices that emit high energy x-rays and electron beams. After use of the first linear accelerators to treat cancer patients in 1953–with lower energy and restricted range of movement–English physicist Frank Farmer developed a comparison between them and other popular machines of the time. This included resonant transformer units, van de Graaff units, and gamma ray units like Co-60 radiation machines.10

In 1962, the conclusions Farmer came to were that LINACs were the ideal choice for larger departments due to a higher price point and hefty size. However, its design at the time left something to be desired. His hopes for linear accelerator improvements included a more robust operation, smaller unit size, and better vacuum systems. Through manufacturers’ dedicated work on improvements up into the 1970s, the LINAC began to fully establish itself as Farmer’s vision came to life with more stable, reliable, compact, and fully isocentric machines.10

Radiation Therapy of Today

After the 1970s, significant changes to linear accelerators slowed. There were no further radical changes to basic structures and concepts for the generation of the x-ray and electron beams. Modern machines became more sophisticated through other improvements. These were advances in beam shaping through the development of multi-leaf collimators, on-board imaging (OBI), and more recently Flattening Filter Free (FFF) designs to permit much greater dose rates. These system and functionality enhancements keep the linear accelerator as the radiation therapy unit of choice for healthcare today.10 Delivering radiation doses deep into cancerous tumors of a patient while minimizing damage to healthy tissue via intensity modulated radiation therapy (IMRT) is achieved confidently with these ever-improving LINACs.

Through the x-ray technologies developed over the last century, scientists continue to develop new methods to safely deliver radiation therapy. Crossing the linear accelerator with the diagnostic imaging capabilities of CT scanners created TomoTherapy®, another radiotherapy option still widely used today. TomoTherapy® machines allow for more precise tumor targeting and preservation of healthy tissue, taking images of cancerous tumors before treatment. The machine will then rotate during treatment to deliver the radiation dose slice by slice, in a spiral-like pattern.11

X-ray radiotherapy is only one type among many cancer treatments now. However, the machines have been honed through the years to create reliable products for healthcare and even veterinary practices. What was once a general, indirect target of radiation exposure has become an extremely pin-pointed, safer technique for the benefit of patients today.

Summary and Conclusion

In summary, x-rays have come a long way since their discovery in 1895 by Wilhelm Conrad Röntgen, revolutionizing medicine. Used for both diagnostic and therapeutic purposes, x-rays underwent significant technological advancements over time starting with producing the first x-ray images on photographic plates. In the early 1900s, the use of x-rays for therapy began with the treatment of skin diseases. By the 1920s, the further developments allowed for the production of higher-energy x-rays. Once in the 1930s, the development of megavoltage x-ray machines allowed for deeper penetration into tissues. Linear accelerators were developed in the 1950s to produce high-energy x-rays and electrons. The 1960s brought the development of computed tomography (CT), which allowed for cross-sectional imaging of the body. In the 1970s, digital radiography was introduced, which allowed for faster image acquisition and processing.

The Versant Physics team has experience that covers a range of equipment including dental units, mobile c-arms and Cone-beam CTs, as well as high energy LINACs and even Proton Therapy units and Cyclotrons. To learn more about how our services can help you, contact us to set up a meeting.

References

  1. History.com Editors. German scientist discovers X-rays. HISTORY. Published July 17, 2019. https://www.history.com/this-day-in-history/german-scientist-discovers-x-rays
  2. ‌Pauwels, Ruben. (2020). HISTORY OF DENTAL RADIOGRAPHY: EVOLUTION OF 2D AND 3D IMAGING MODALITIES.
  3. History Of X-Ray Imaging • How Radiology Works. Published March 12, 2021. https://howradiologyworks.com/history-xray-imaging/
  4. ‌X-Ray Technology: The Past, Present, and Future :: PBMC Health. www.pbmchealth.org. Accessed March 24, 2023. https://www.pbmchealth.org/news-events/blog/x-ray-technology-past-present-and-future#:~:text=Quickly%2C%20military%20doctors%20realized%20the%20life-saving%20potential%20X-rays
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01 Oct 2021
Cancer Treatment, Molecular Imaging, Radiation Therapy Versant Physics 0 comment

How Molecular Imaging and Radiation Therapy Help Fight Breast Cancer

It is estimated that 1 in 8 women in the United States will develop invasive breast cancer within their lifetimes. It is an incredibly devastating disease that affects thousands of people a year. This year alone, 281,550 women in the United States will be diagnosed.

Screening efforts and treatment therapies involving molecular imaging and radiation therapy are key to helping detect and successfully treat breast cancer.

Breast Cancer Statistics

  • Breast cancer is the most diagnosed cancer in women.
  • Breast cancer in women has the highest rate of death compared with any other cancer, besides lung cancer.
  • It is more commonly diagnosed in black women under the age of 45 than white women.
  • Minority women are 72% more likely than white women to be diagnosed with breast cancer before age 50 and are 127% more likely to die of breast cancer before age 50.
  • Men have a 1 in 833 chance of getting breast cancer.
  • In 2021, the World Health Organization reported that breast cancer accounted for 12% of all new, worldwide cancer cases.

Breast Cancer Risk Factors

Age and being born female are the biggest risk factors for breast cancer. Women that have direct relatives with a history of breast or cervical cancers such as mothers, sisters, and grandmothers have a higher risk of developing breast cancer in their lifetimes.

There are several known gene mutations that can be inherited from either parent which grant a higher lifetime risk of developing breast cancer as well.

When functioning correctly, these genes, called Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2), produce proteins that help repair DNA. These tumor suppressor proteins actually help protect from certain cancers by slowing abnormal cell growth and forcing certain damaged cells to stop working entirely.

However, when present, the BRCA gene mutation can prohibit these proteins from working and building correctly, resulting in cancerous tumors.

By age 80, 55%-72% of women with an inherited BRCA1 mutation and 45%-69% with an inherited BRCA2 mutation will develop breast cancer. People with a BRCA variant also tend to develop breast cancer at a much younger age than those without.

There are also higher instances of BRCA1 and BRCA2 gene mutations in certain racial and ethnic groups. For instance, 2% of Ashkenazi Jewish people carry one of the variants. A study in 2009 determined that black and Latin American women were more likely to have BRCA1 mutations.

Signs & Symptoms

The most common symptoms of breast cancer include a lump or mass in the breast, but physical changes in the appearance of the breast are also reported. This includes skin redness or swelling, bloody or abnormal discharge, thickening of the skin, or scaliness.

Breast cancer can develop without presenting any physical symptoms, however, which is why regular screening and breast exams are so important for prevention.

Screening Recommendations

Regular breast cancer screenings can help discover breast cancer in its early stages before it has spread to other parts of the body, therefore, limiting treatment options and increasing mortality rates. Mortality rates can be reduced by 40% with regular screenings.

Mammography

Mammography is a low-dose x-ray procedure used to detect breast cancer in its early stages, often before a patient has experienced any symptoms like lumps or skin alterations.

This type of x-ray exam exposes the patient to low doses of ionizing radiation to produce an image of breast tissue or the inside of the breast.  

During a mammography procedure, the breast is flattened between two plates on the x-ray unit for several seconds while an x-ray beam is carefully aimed at the area of concern by the radiologist or technologist performing the procedure. It is standard during a normal screening for two views of each breast to be taken. The mammograms are then reviewed by a radiologist, who looks for early signs of cancer or other abnormalities.

Mammograms can also be used if a patient has experienced symptoms of breast cancer and to screen patients who have been previously treated for breast cancer. This diagnostic mammogram includes additional views of the breast not normally taken during a screening.

Radiation received from regular mammograms is cumulative, however, it does not significantly increase breast cancer risk. In the case of screening for cancer, it is more beneficial in the long run to receive a low radiation dose. 

Screening Frequency

Various medical and cancer-related institutions have different guidelines on when it is appropriate or necessary to schedule a mammogram.

The American Cancer Society recommends patients with an average risk of breast cancer between the ages of 45-54 get annual mammograms. Patients aged 55 and older have the option to get a mammogram every other year.

The American College of Radiology (ACR) and the Society of Breast Imaging (SBI) recommend annual mammograms begin at age 40 and continue past age 74.

Molecular Imaging & Breast Cancer

Molecular Imaging is a medical imaging procedure used to help locate breast cancer tumors and determine if cancer has spread to other parts of the body. It is a vital part of the diagnosis and treatment process because it measures biological and chemical processes within the body, compared with regular x-rays which focus on static anatomical images.

Molecular imaging helps physicians determine the appropriate treatment therapies, study the patient’s response to drugs, and closely monitor changes in cellular activity. It is also useful for identifying whether the prescribed therapies are effective and monitoring for reoccurrences.

There are a variety of medical imaging procedures that help visualize chemical processes in the body such as blood flow, oxygen use, or metabolism. Many procedures require an imaging agent such as a radiotracer—a compound containing a small amount of radioactive material—being introduced into the body usually via injection into the bloodstream.

This radiotracer is designed to accumulate in the body in different organs which are then picked up by the imaging device.  It can also attach to different cells or groups of cells and paint a clear picture about precisely where abnormal amounts of metabolic activity are occurring.

PET/PET-CT

Positron Emission Tomography (PET) scans alongside Computer Tomography (CT) are one of the most common molecular imaging technologies used for breast cancer. The combination of these two imaging modalities helps physicians determine the exact location of the tumor, what stage the cancer is at, if it has spread, and what type of treatment will be best moving forward.

In this procedure, a radiotracer that naturally emits positrons as it decays is injected into the bloodstream. These positrons react with electrons in the body and produce energy in the form of photons. These photons are detected by the PET scanner, producing 3D images which show how the radiotracer is being distributed.

On a PET scan, the areas where the radiotracer has accumulated appear brighter and more intense than in the surrounding tissue. This is because cancer cells, when active, absorb more glucose. The higher instance of this metabolic activity is made clear thanks to these “hot spots” on the PET scan.

The PET scan is combined with the CT scan to produce a detailed image of both the patient’s anatomy and the metabolic activity present.

Surgical Treatment Options

In addition to chemotherapy, there are several other treatment options for breast cancer that typically precede radiation therapy.

Lumpectomy

A lumpectomy, also known as a partial mastectomy, re-excision, or biopsy, is a breast-conserving surgery that involves removing part of the breast tissue. The surgery removes the lump or tumor plus a small amount of the healthy tissue that surrounds it.

Mastectomy

A mastectomy is a surgical procedure that removes the entire breast. There are different kinds of mastectomies with varying degrees of severity. The type of mastectomy a patient receives will depend on the stage the cancer is at and if it has spread to the lymph nodes or other areas of the body. 

Radiation Therapy & Breast Cancer

Radiation therapy delivers ionizing radiation particles to specific areas of the body to destroy cancer cells, either as a standalone treatment or in conjunction with other treatment options like surgery. Brachytherapy and External Beam Radiation Therapy are the two most common treatment types.

Brachytherapy

Brachytherapy is a procedure that involves placing small, sealed radioactive material sources inside the body, either directly inside or next to a tumor. Also known as internal beam radiation, this procedure is used to treat cancer by allowing doctors to deliver higher doses of radiation via a needle or catheter to specific areas of the body.

Compared to other types of radiation treatments, brachytherapy is best for cancers that have not metastasized. It is considered as effective as—and sometimes used in conjunction with—external beam therapy. Due to the nature of brachytherapy procedures, there is a smaller chance of radiation exposure to surrounding healthy tissue and organs than with external radiation as it targets the tumor directly.

Because healthy tissue and organs surrounding the tumor are not as affected by the radiation treatment, most people experience few or less serious side effects than occur with external beam therapy. In addition to tenderness, bleeding, or swelling at the treatment area, the side effects a patient could experience depend largely on the type of cancer and therapy being performed. Fatigue is common.

External Beam Radiation

According to the American Cancer Society, external beam radiation is the most common type of radiation therapy used to treat breast cancer. It can be used in both early-stage breast cancer as well as for advanced stages that cannot be removed with surgery.

EBRT normally occurs 3 to 6 weeks after a patient has undergone surgery and/or completed chemotherapy. Small doses of ionizing radiation are delivered to cancer to destroy the cancerous cells. This process is normally a painless outpatient procedure that lasts up to 5 days a week for anywhere from 2 to 9 weeks.

During EBRT, the patient is usually positioned on their back with their ipsilateral arm placed above their head and their shoulder rotated outward. Then, radiation is precisely applied to the area according to the radiation treatment plan.

Throughout the process, a radiation oncologist monitors a patient’s response to the treatment and may alter the prescribed radiation dose or the number of treatments accordingly.

One 2021 study suggests that a lumpectomy plus radiation therapy offers better survival rates than a standalone mastectomy for early-stage breast cancer. Other studies have discovered that the risk of recurrence in a patient who undergoes radiation therapy is between 5% to 10%, while patients who do not receive radiation therapy have a 20% to 40% recurrence rate.

The Radiation Therapy Team

Each patient who undergoes radiation therapy has a dedicated team of radiation professionals on their side who determine exactly how they will be treated. Throughout the treatment process, they also determine if any changes to the radiation treatment plan need to be adjusted.

A radiation oncologist is a specialist in treating cancer with radiation. Their job is to determine which therapy is the best fit for the patient based on their medical history and physical health.

A medical physicist and dosimetrist will also be a part of this team. They work together with the physician to create the treatment plan.

Radiation therapists and technologists are the individuals who physically administer the radiation therapy treatments and operate the equipment. They are the people patients will interact with the most during their treatment.

The Takeaway

There are a variety of available breast cancer treatment therapies including radiation therapy and surgery. Radiation therapies administered in conjunction with chemotherapy and surgical treatment options have a much lower recurrence rate than standalone treatments.

Proper screening and regular exams are the best way to detect breast cancer when it is in its earliest and most treatable stages. If a patient is 40 or older, it is in their best interest to begin scheduling annual mammograms.

In honor of Breast Cancer Awareness month, check out the following organizations providing patient support services and making great strides in research and awareness:

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