Looking Inside the Body Without Surgery

If a person goes to the doctor with a rash, an infected cut, or a sore throat, the doctor may learn a lot just by looking at the patient closely, asking questions, or doing a simple test. But many health problems are hidden deep inside the body. Think, for instance, about a broken bone, a tumor growing within an organ, or abnormal blood flow through the heart’s blood vessels. In these and many other cases, doctors need tools that allow them to see what is happening beneath the skin—ideally without opening up the body with surgery.

Medical imaging is a group of methods that can provide the inside view that doctors need. These methods generate “pictures” that help doctors find the source of a problem or check that body processes are happening normally (Figure 1) [1]. Beyond diagnosis and routine exams, medical imaging can also guide tools to the right place during procedures and check whether treatments are working. In research, imaging also helps scientists study how diseases develop and test possible new therapies.

Each type of medical imaging is best for a specific job. X-rays are very good at showing hard tissues, such as bones, so they are often used to find fractures. Computed tomography (CT) scans use X-rays from many angles to build more detailed pictures, which can be useful when doctors need a clearer view of an organ or tissue. Ultrasound uses sound waves to look at organs, blood flow, or babies developing before birth. Magnetic resonance imaging (MRI) uses strong magnets and radio waves to spot problems in soft tissues such as the brain, muscles, heart, liver, or kidneys.

Medical Imaging is Challenging

Getting useful internal images is much more difficult than taking a picture with a camera. A camera collects light bouncing off the outside of an object, but medical imaging collects signals that come from deep inside a patient. In most types of imaging, a machine sends some kind of energy (X-rays, sound/radio waves, or light) into or through the body. Different tissues affect that energy in unique ways. Bone, for example, blocks X-rays strongly, while sound waves can bounce off soft tissues. A detector picks up the signals that bounce back or pass through, and a computer turns those signals into an image.

Each method has its limits. The signals coming back out of the body must often pass through layers of skin, fat, muscle, blood, bone, and moving organs before they reach the detector. Along the way, signals can become weaker, blurrier, or mixed with “background noise” from nearby tissues. So, CT and MRI, which can see deep below the surface, may not show tiny details very clearly. X-rays and CT scans also use radiation, so doctors must think carefully about when and how often to use them. Due to these limits, researchers are working on making medical imaging clearer, safer, and more useful for understanding what is happening inside patients’ bodies.

(Not So) Rare Earth Metals Can Improve Medical Imaging

One way to improve medical images is to use special materials that can be given to the body before or during a scan, often by injection. The job of these materials is to create a signal that is easier to detect, or to help a certain type of tissue or problem area stand out from its surroundings. Metals called lanthanides are promising in this regard. If you have studied the periodic table, you might know lanthanides as “rare earth elements” (Figure 2). Lanthanides are not always “rare” in the ground, but they are usually spread out in rocks and minerals and can be difficult to mine, separate, and purify. Lanthanides are particularly useful for imaging because they interact with light, X-rays, and magnetic fields in unusual ways, creating various kinds of signals depending on which lanthanide is used and how it is “built into” an imaging material [2].

Carriers for Holding Lanthanides Safely

Unfortunately, doctors cannot simply inject loose lanthanide ions into a patient’s body—they can harm tissues and organs. To get around this, lanthanides are placed inside carriers: tiny structures that hold the lanthanide, help deliver useful signals safely, and control how they behave inside the body. Some carriers are already used in medicine, but researchers are continuing to improve carrier design. Lanthanide carriers can include nanoparticles, which are extremely small, solid particles; chemical “cages”, which are small molecules that hold lanthanides tightly; and proteins similar to those already used by living things (Figure 3A).

In addition to protecting the patient, lanthanide carriers may help solve some common imaging problems. They can act like tiny signal-makers inside the body, by absorbing some of the energy sent in and giving off their own light—strengthening the returning signal and making it easier to detect. For example, some nanoparticle carriers tuck the lanthanides inside a crystal-like structure—a solid material in which atoms are arranged in an orderly pattern—that protects the signal from being weakened by the bodily environment. Certain chemical “cages” can collect energy from incoming light and pass it to the lanthanide, helping it glow more strongly. Carriers can also stop lanthanide signals from fading too quickly, giving doctors and researchers more time to observe the imaging material.

Even a strong signal is not helpful if it comes from the wrong tissue, and certain lanthanide carriers could help guide the imaging material to the right place. Nanoparticles can be coated with substances that allow them to move through body fluids more easily or collect near certain tissues. Protein-based carriers offer an even more specific approach, because proteins can sometimes be designed to recognize and stick to particular cells, tissues, or disease-related signals. Overall, the carrier is not just a package for the lanthanide—it is an active part of the imaging tool.

Better Signals, Better Answers

Researchers are actively investigating how new lanthanide carriers could improve various types of medical imaging (Figure 3B). A scan is most useful when it helps doctors or researchers answer a medical question: Where is the problem? How clearly can we see a tumor’s edges? Is it changing over time? Is a treatment reaching the right place? The examples below show how lanthanide carriers are being studied for near-infrared (NIR) imaging, X-rays, and MRI.

Near-Infrared Imaging: Signals From Deeper Tissues

Some lanthanide carriers may be extremely useful in NIR imaging. NIR is a type of light just beyond the red light human eyes can see (Figure 1E). NIR can travel deeper into the body than visible light can, making it a good choice when clear pictures of deep tissues or organs are needed [3]. (To learn more about how NIR imaging is used, you can read this Frontiers for Young Minds article, or this one).

Cells and tissues are constantly changing: heating, cooling, stretching, pulling, swelling, shrinking, and moving water and other materials in and out. Using lanthanide carriers, NIR may be able to detect some of these minute changes in the body’s internal environment. For example, one type of cancer treatment heats tumors up to destroy them, and doctors may be able to use NIR with lanthanide carriers to determine whether the tumor is getting hot enough while nearby healthy tissue stays protected. Studying how nerve cells move small packages of materials along their long, thin branches is another cool example [4]. If NIR imaging shows that movement has slowed down or become disorganized, that can be a clue that the cell is unhealthy. Bright, stable lanthanide carriers may help researchers follow these tiny moving packages.

Stronger, Longer-lasting X-Ray Signals

Bones stand out well in X-rays because they block more X-rays than softer tissues do. Some lanthanides can help with this because they absorb X-rays strongly. If they collect in the area doctors want to study, fewer X-rays pass through that area to the detector, so the area stands out more clearly in the image.

Other lanthanide carriers work differently. Materials called scintillators can absorb energy from the X-rays that enter the body and then give off light, creating a signal that can be detected, basically “lighting up” the area that doctors are interested in [5]. Some lanthanide scintillators can even keep glowing for a while after the X-ray source is turned off. This is called afterglow, and it is useful because a longer-lasting glow can reduce the amount of radiation a patient must be exposed to [6, 7].

Making Soft Tissues Stand Out on MRI

MRI is especially useful for looking at soft tissues, such as the brain, muscles, heart, liver, and kidneys. But even with MRI, certain tissues, blood vessels, or problem areas may need extra help to stand out clearly from the surrounding tissue. Doctors can sometimes give patients contrast agents, which are substances that make certain parts of an image easier to see.

One lanthanide, gadolinium, is already used in some MRI contrast agents. Gadolinium changes signals from nearby water molecules, which can make certain tissues appear brighter or clearer in the scan. In current contrast agents, the gadolinium is held in a chemical “cage” to keep it from causing harm. However, some new nanoparticle carriers may strengthen the MRI signal even more. As we mentioned earlier, protein-based carriers can be designed to recognize particular cells or tissues, helping the imaging material collect in the area doctors need to examine [8]. Researchers’ overall goal is to create MRI contrast agents that are stronger, more targeted, and safer for patients.

From Discovery to Patient Care

One of the most exciting things about lanthanide carriers is their flexibility. By changing the lanthanide or the carrier, researchers can design imaging materials that are “just right” for different jobs. In some cases, they may even design one carrier that produces more than one kind of signal.

This flexibility provides many possible combinations to explore. But before lanthanide carriers can be used to help patients, researchers must verify that they are both accurate and safe. A signal that works in the laboratory might not behave the same way inside a living cell, tissue, or organ. Researchers need to understand where an imaging agent travels in the body, how long it stays there, and how it leaves. Before doctors can use them in patients, new imaging materials must go through strict safety testing, which can take a long time.

Researchers must also think about the planet. Mining and refining rare earth elements can be expensive and can harm the environment if not managed carefully. If lanthanide-based imaging becomes more widely used, researchers will need to consider recycling, safer mining and processing methods, and whether other materials could replace lanthanides in some cases.

Overcoming these challenges matters because medical images guide important decisions about people’s health. If researchers can address the questions about safety, reliability, and sustainability, lanthanide carriers could become part of a new generation of imaging tools that could allow doctors to see inside the body more clearly, helping them find diseases earlier, plan treatments more carefully, and improve patient care.

Glossary

Medical Imaging: ↑ Methods doctors use to look inside the body without surgery, creating pictures that help them find problems, guide procedures, and check whether treatments are working.

Lanthanides: ↑ A group of metals, also called rare earth metals, that can interact with light, X-rays, and magnetic fields in useful ways, making them useful for medical imaging.

Carriers: ↑ Tiny structures that hold lanthanides, helping deliver their signals safely and control how the imaging material behaves in the body.

Nanoparticles: ↑ Extremely small particles, much too tiny to see with your eyes. In imaging, they can carry lanthanides and control how the signal behaves.

Scintillators: ↑ Materials that absorb X-ray energy and give off light, creating a signal that can be detected by imaging equipment.

Afterglow: ↑ Light that continues for a while after the energy source that activated a material is turned off.

Contrast Agents: ↑ Substances given before or during medical imaging to make certain tissues, blood vessels, or problem areas easier to see.

Gadolinium: ↑ A lanthanide used in some MRI contrast agents because it changes signals from nearby water molecules, making certain tissues easier to see.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We wish to thank Dr. Susan Debad for providing us with a first draft and for her continued collaborative input. We would also like to thank the coauthors of the original manuscript: Zixuan Chen, Mingyu Sui, Hongxuan Wang, Marco Bettinelli, Luís D. Carlos, Daniel Jaque, Oscar L. Malta, Jorge Méndez-Ramos, Cyrille Richard, Bruno Viana, and Ka-Leung Wong. This work was supported by the National Research Foundation (NRF), Prime Minister’s Office, Singapore, under the NRF Investigatorship Program (award no. NRF-NRFI052019-0003), the National University of Singapore (NUS) NANONASH Programme (NUHSRO/2020/002/NanoNash/LOA; R143000B43114). The funders were not involved in the work’s conception, interpretation, writing of this article, or the decision to submit it for publication.

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