100 incredible years of physics – medical physics
If he were alive today, Major Charles E. S. Phillips – one of the founders of the IOP and Honorary Treasurer from 1929 to 1945 – would have certainly approved of the most recent recipient of the award named in his honour. This is because 2019 IOP Phillips Award winner Dimitra Darambara is, like Phillips in his time, a pioneer in the application of physics to medicine.
Darambara is former Chair of the IOP Medical Physics Group, which works to promote and increase the visibility of medical physicists. She uses her experience and knowledge from experimental high-energy physics at CERN and applies it to build medical imaging techniques and technologies that can assist cancer diagnosis and effective treatment. “My main motivation is to design and develop detectors and imaging systems that can have a real impact on human lives and in particular on the lives of cancer patients,” she says. “Moving from a basic detector concept to clinical necessity fascinates me.”
For the past 10 years, Darambara has been busy developing a new type of detector that is now very close to being ready and that she believes will spark “a revolution in X-ray imaging”. As the name implies, photon-counting multispectral X-ray imaging uses novel photon-counting detectors to look at the properties of every single photon received after having passed through a patient’s body. It will allow 3D, low-dose, high-resolution, non-invasive, specific and quantitative imaging, solving a host of problems with conventional X-ray imaging. For example, calculations suggest the technique will mean patients receive a 30–40% lower dose of radiation compared to today’s X-ray imaging. Darambara continues: “It’s also going to be, for the first time, tissue-specific imaging, which means that it’s going to be quantitative and, therefore, a step closer to precision medicine.”
Link to the past
In terms of both driving technology forward and reducing the harmful effects of X-ray imaging, Darambara’s work can be linked all the way back to Phillips’ pioneering efforts as the first physicist to be appointed to work in a hospital; the Cancer Hospital, London (now the Royal Marsden NHS Foundation Trust). “I think that we all agree that he was the first true medical physicist,” adds Darambara. At the Cancer Hospital, Phillips – one of the leading figures in developing medical applications for the X-ray after its discovery in 1895 – worked until his retirement in 1927 on the fundamental science behind radiotherapy, as well as techniques for manipulating radioactive substances and radiation protection.
Phillips may have made important early contributions to protecting patients and doctors from the harmful effects of radiation. But even in 1927, appalling radiation injuries were still commonplace. It took the ingenuity of Phillips’ successor at the Cancer Hospital – William Valentine Mayneord – to turn this around. Mayneord developed the scientific basis for radiation dosimetry and protection that, even today, underpins modern medical physics.
Though she admires both Phillips and Mayneord for their “extraordinary work”, Darambara regards her research as stemming from two later innovators in medical physics: “Since I try to design and develop new imaging systems, Hounsfield and Mansfield are my predecessors because their work was fundamental for imaging and they translated basic physics into clinically useful technology” she says.
Godfrey Hounsfield (IOP Dennis Gabor Medal and Prize winner) pioneered X-ray computed tomography (CT) in the 1960s and 70s. The dawn of the Information Age provided him with the capability of programming a computer, so that it could interpret X-ray signals and form a 2D image of a complex object. He then used this insight to build a machine that could send multiple X ray beams through a human at different angles and detect how the beams pass through to construct an internal image. In 1971, his first prototype head scanner – now standing in the Science Museum alongside the Apollo-10 lunar module – revealed a brain tumour in a 41-year-old female patient.
Around the same time, Peter Mansfield (IOP Honorary Fellow and Dudley Medal and Prize winner) was developing magnetic resonance imaging (MRI). His key contribution came in 1973 when he solved how to localise the radio signals from magnetic resonance on a slice by slice basis. He refined the method and produced in 1976 the first demonstration of live human anatomy by scanning the finger of a PhD student, and then the first body scan of himself in 1978.
Darambara credits Hounsfield and Mansfield as having “one of the highest impacts in medical physics, and in cancer diagnosis and treatment, and in any disease that benefits from these kinds of imaging.” But she also acknowledges the impact of World War II, as well.
For example, primitive ultrasonic scanners date back to the 1930s, but the War accelerated technological development, allowing the first human ultrasound pictures to be taken around 1950. A more surprising upshot of World War II came from attempts to construct the most destructive weapon in history: the atom bomb.
The medical groups of the Manhattan Project built devices to quantify radiation amounts in order to understand what procedures and protection were required for those working on the project. “Many people say that this was one of the positive consequences of the Manhattan Project,” says Darambara. This is because these Manhattan Project-developed medical devices are the progenitors of nuclear imaging techniques that rely on radioactive tracers and are now used to diagnosis disease and monitor treatment, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT).
Merging modalities and disciplines
Today, clinicians have a host of techniques at their disposal to non-invasively delve into the human body in order to diagnose and treat disease. For example, alongside ultrasound, PET, SPECT, MRI and X-ray imaging, intensity-modulated radiation therapy (IMRT) uses computer programs to precisely deliver beams of energetic electrons or X-rays from linear particle accelerators to malignant tumours, killing cancerous cells and minimising the dose to surrounding healthy tissues.
Research continues to try to improve these methods in a range of different ways, often by building hybrid imaging techniques. This might mean combining PET with MRI (PET-MR) or SPECT or PET with CT. “PET-MR is a challenging technological advancement, but is there a revolutionary application, is it going to be cost effective?” asks Darambara. “It’s not for us as physicists to just do physics because that’s what we love to do – we have to provide quantitative assessments and evidence for clinical utility and solutions to unanswered clinical problems, as well.”
One hybrid imaging technique Darambara feels has huge clinical potential is being investigated in a project co-led by Simon Cherry – current Editor-in-Chief for Physics in Medicine & Biology, published by IOP Publishing on behalf of the Institute of Physics and Engineering in Medicine. Named EXPLORER, Cherry’s project aims to build the world’s first total-body PET scanner combined with a low-dose CT scanner. Although in 2018, EXPLORER took its first human images, Darambara says that the technique is not ready for the clinic. However, when it is ready, it will be 40 times more sensitive than current PET for total body imaging, and will produce higher resolution images with enhanced image quality.
“They will be able to simultaneously image the entire human body and perform total body dynamic studies across all the organs and tissues of the body – something that is not possible with what we do nowadays,” she adds. “I would have liked to have worked on this project – I’m very jealous – because in the same way that we work on a revolution in X-ray imaging, I think this is a revolution in PET.”
Looking further into the future, Darambara sees two trends in medical physics becoming key to exposing the underlying biology of disease in the next 100 years. The first is multi-modality imaging – where several signals from more than one imaging technique are produced simultaneously. “There is no single imaging modality that can give you all the information you need either in diagnostics or in treatment,” she says. “But when we combine different modalities, we can have the morphological (anatomical) information and the metabolic (functional) information to allow us to gain more knowledge about what is happening regarding the biology behind the images.”
The second trend is moving from a one-size-fits-all medical approach to personalised medicine. To get there and be able to find the best treatment for each individual patient will again require the combination of a number of different technologies, including multi-modality imaging. “In a way, we are trying to say that images are not just nice pictures, but they are data and data is knowledge; there are quantifiable parameters within them that we can use to understand the underlying biology,” explains Darambara. Extracting and subsequently mining this quantitative information is called radiomics. Selecting appropriate imaging characteristics from radiomics and correlating them with the genomic profile and patterns of a patient – known as radiogenomics – could offer unprecedented insights at the genetic and molecular level that help to determine disease progression and the response to treatment for individual patients. Further, integrating machine learning, multimodality imaging and radiogenomics techniques in a holistic manner will help medical physicists build accurate prediction models for diagnosis, disease progression and therapy response assessment – the ultimate goal of fully patient-centric personalised medicine.
Though progress has been made in all these techniques, Darambara feels a multidisciplinary approach is key to unlocking the full potential of personalised medicine, and driving medical physics forward more generally. “We should bring the insights of other parts of physics like nuclear physics, high energy physics and astrophysics into medical physics, but also embrace insights from life sciences scientists, clinicians, bioengineers and data scientists to translate fundamental discoveries and/or ground-breaking technological developments into the clinic, so that we can work together to improve patients’ lives,” she concludes.
|Gustaf Ising proposes the linear accelerator, which would be used in radiotherapy decades later||1924||Marxist revolutionary and Soviet leader Vladimir Lenin dies|
|Ernest Lawrence patents the cyclotron, a device that produces small quantities of artificial radioactive isotopes, which were soon put to use in medicine||1932||Notorious US gangster Al Capone is convicted of tax evasion|
|Karl Dussik is the first to use ultrasonic waves as a diagnostic tool||1942||Disney film ‘Bambi’ premieres|
|The first clinical positron imaging device is built to detect brain tumours||1952||The Diary of Anne Frank published|
|Basil Hirschowitz passes a prototype fibre-optic endoscope down his own throat||1957||An outbreak of Asian flu kills over 1 million people|
|Laser treatment pioneered in an operation to destroy a retinal tumour||1961||Yuri Gagarin becomes the first human to journey into outer space|
|Godfrey Hounsfield builds a full-body CT scanner||1975||Microsoft created by Paul Allen and Bill Gates|
|Peter Mansfield conducts the first MRI body scan on himself||1978||Louise Joy Brown – the world’s first ‘test-tube baby’ – is born|
|The first patient is treated with intensity-modulated radiotherapy||1994||South Africa holds multi-racial elections for the first time after apartheid|
|EXPLORER – the world’s first total-body PET/CT scanner – takes its first images||2018||Aged 15, Greta Thunberg starts spending her school days outside the Swedish parliament calling for action on global warming, sparking school climate strikes globally|