Inside Motion — Or how to track mobile tumors

A cancer diagnosis turns life upside down. It comes with uncertainty and suffering, not only for the patients but also for their families and friends. But not all cancers are alike.

According to the WHO’s World Cancer Report, lung cancer ranks first both in terms of incidence and mortality compared to other common sites of cancer. This is one of the reasons why we focus on lung cancer in our research project.

Our team consists of medical doctors, MR physicists, engineers, and computer scientists. These researchers come from the University Hospitals of Basel, Geneva and Zurich, the University of Basel, and the Paul Scherrer Institute (PSI) in Villigen. Together we strive to advance lung cancer treatment.

In what follows, I am going to write about the cutting-edge research project we are currently developing in our interdisciplinary group from a physical and engineering point of view. When I first studied mechanical engineering, I was hoping that my work will have an impact on society one day. I specialized in robotics while always keeping medical applications in mind. And yet, I never dared to dream that I would actually end up working on lung cancer treatment. But fortunately, here I am, and so let’s dive into the fascinating world of biomedical engineering.

Different treatment strategies

There are several ways to treat lung cancer. You have probably heard of surgery, chemotherapy, or radiotherapy. Which of these will be applied depends on the type and stage of a cancer. Often a combination of different treatment strategies is applied.

In radiotherapy, on which I focus in my research, high energy beams are shot at a tumor from outside the body. This causes the DNA of the cancerous cells to be damaged and the cells to be destroyed.

In conventional radiotherapy, the energy is delivered by photons. These are elementary particles with zero mass. On their way through the body, photons continuously deposit radiation dose. The dose decreases as the photons travel further.

Unfortunately, photons don’t distinguish between good and bad cells. This means healthy tissue in the beam path gets irritated and possibly destroyed. This is where the protons come into play.

The advantage of protons

Unlike photons, protons carry a mass and a single positive charge. Hence, by applying a magnetic field protons can be steered, focused, and formed into beams with desirable properties. At a specific, predefined penetration depth, the proton beam comes to an immediate stop, and a large share of the energy is transferred to the tissue. The increase in radiation dose at this specific penetration depth is called Bragg peak. Beyond the Bragg peak, radiation dose drops to zero within millimeters.

Physical properties of photons and protons. Courtesy of PSI.

Now, let’s draw

Imagine the diameter of a pencil. This is normally in the range of 5 to 7 mm. If you could form a proton beam with its diameter similar to a pencil, you could scan a tumor like coloring in a picture — but in three dimensions: spot by spot, line by line, plane by plane. We can exactly do this with a proton beam by dynamically adapting its direction and configuring its penetration depth.

The PSI pioneered and developed the so-called pencil-beam scanning proton therapy which allows to deposit the radiation dose inside the body with extremely high precision. Since 1996 the pencil-beam scanning technology was applied to tumors located near sensitive organs, such as eyes, brain or spinal column.

The lungs and heart are also critical structures which need to be protected. Thus, pencil-beam scanning techniques could have significant advantages for the treatment of lung tumors while trying to protect healthy lung tissue and the heart. However, in a living human, they are in constant motion, our canvas is moving under the pencil, which makes it much harder to draw in a tumor.

The burden of motion

Proton-beam scanned therapy normally consists of several treatment sessions, each of which lasts some tens of minutes. Needless to say, we can’t ask patients to hold their breath for the entire treatment session. Worse still, holding their breath for even a couple of seconds can be challenging for lung cancer patients. The lungs, the heart and with them the tumors are constantly moving due to the breathing motion and the heartbeat. The benefits of increased accuracy only come to fruition when the tumor’s shape, location, and motion is precisely known at every point in time so it can be followed.

It is the goal of my project to provide the MR physicist and medical doctors at PSI with a patient-specific motion model. Not only do we want to know the pose of a tumor at the current point in time but we further aim to anticipate future organ states, up to half a second in advance. This gives the treatment system enough time to steer the proton beam to the correct position. In other words, my project is all about tumor tracking.

From 3D to 4D

The animation you see in the leading image is a so-called 4D MRI. It marks the first step on a long road to a complete cancer treatment plan. A 4D MRI is basically a 3D film of the chest with the time as the 4th dimension. It is like putting your 3D goggles on and watching through a person while they are breathing. The 4D MRI gives a good understanding of the patients breathing motion and is crucial for tumor tracking.

Unfortunately, it is not possible to take a 3D MRI snap-shot of the chest since the acquisition time is too long. To image the entire volume we need a couple of seconds — or approximately half a breathing cycle. As a result, the 3D image shows strong artifacts. What we’re doing instead is to acquire a lot of 2D slices at different positions within the body and a posteriori combine them into reasonable 3D images.

How do we know which slices belong together? Which 2D images were acquired at ‘similar’ breathing states? For this we use ultrasound. More specifically ultrasound imaging of the liver.

But wait, why the liver? So far have been talking about lung cancer, why do I care about the liver? This is because ultrasound can’t image the lungs. There is too much air which prevents ultrasound waves to travel further. However, as the liver is also moving due to breathing, we can deduce the breathing state of the lung by looking at the liver.

This is an ultrasound film of the liver and the diaphragm. Don’t feel bad if you don’t recognize anything. Ultrasound images are difficult to interpret. It took me quite some time to learn how to operate the device and to understand what I actually see on the images.

Ultrasound imaging has the main advantage that it can record breathing data during proton treatment, which is not possible for MRI. In a nutshell, we use MRI to image the lung structures, the tumor shape, and the motion of a tumor induced by breathing before the treatment. And we use ultrasound of the liver as a surrogate for breathing state detection in pretreatment imaging, motion modelling, and on-line tumor tracking during dose delivery.

Step by step…

In a first step, we perform simultaneous 2D MRI and ultrasound imaging. This is however not trivial as normally you should not bring any electronic devices or magnetic materials into the MR scanner since they are causing major problems. Freely movable magnets are accelerated by the strong magnetic field of the MR scanner and, in the worst case, may act as dangerous projectiles. The MR-compatible ultrasound probe we use was specifically developed for our application. It contains no magnetic material and its electronic parts are shielded by a protective copper layer.

Given the ultrasound images of the liver, we build one 3D MR volume for each breathing state during a couple of breathing cycles. Based on these image pairs — ultrasound image of the liver and 3D MRI of the lungs — we compute a correlation model.

In the meantime, the medical doctors and MR physicists design a treatment plan. That is, they define how much radiation dose should be delivered to each spot within and around a tumor.

During proton treatment, the patients are lying on their back with the ultrasound probe attached to their belly. On-line ultrasound images are used to drive the motion model and to predict the pose of a lung tumor in real-time eventually allowing us to distinguish between good and bad cells.

… towards patient treatment

So far we have gained good experience with volunteer data. We are prepared to process first patient data in the near future with the aim to bring all benefits of proton therapy to lung cancer patients.

If you want to learn more about medicine in the fourth dimension, save the date for the upcoming exhibition at Pharmaziemuseum Basel:

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