This week it happened. I broke the first bone in my life. I even got three fractures at once, something called a zygomaticomaxillary complex fracture (those are several bones around your eye), caused by a stupid bike accident (wear a helmet kids, they save lives). And while I was lying there, in this pretty impressive machine performing the CT scan, I had to think about what was actually happening. On an atomic level.
The nurse leaves the room, you hear some noises, and that’s it. You feel nothing. Even though, a huge number of immensely energetic photons just got blasted through your body. And in the end, you get this picture of your skull where the doctor tells you the position of your fracture, or why your teeth hurt or some other unpleasant fact about your body.
Nevertheless, we should be happy about having access to such a diagnostic tool. That’s why today, I want to share some of the fascinating background of x-radiation, and how we use it in life sciences and medicine.
X-ray scan and CT scan are the same thing. MRI is different.
Everyone knows the application of x-rays in medicine, of course. We use them as an imaging technique, so we get a picture of the interior of our body. X-rays allow us to distinguish bone from soft tissue. That comes especially handy when looking for fractures like in my case, but also to see cavities or infection in your dentist’s practice, or to locate the exact position of a tumor. Some notes to avoid confusion: A CT scan is basically an x-ray scan, that gives you a 3D picture. This can be done by rotating the x-ray source and detector around you and putting the slices back together with a software. You can get a similar result from an MRI scan. But the physical background is entirely different, so don’t mix them up. X-ray imaging works because some atoms absorb x-rays, while others don’t. MRI works, because small magnets in our atom’s nuclei behave different in soft tissue than in solid tissue. But let’s not get carried away, this is about x-rays.
A quantum-mechanical intermezzo
Why do x-rays let us distinguish bone from soft tissue? To understand this, we have to understand first what x-rays are, and how they interact with matter. You know photons, these light particles, that also behave like a wave (keywords for the curious: particle-wave duality). They come in different energies, and this energy is inversely proportional to their wavelength. So, long-wavelength photons have low energy (radio waves, microwaves), and short-wavelength photons have high energy (gamma rays, x-rays), and somewhere in between is our visible light, sandwiched by infrared light (lower energy) and ultraviolet light (higher energy).
X-rays are photons of a really high energy. Dangerously high, even. That’s why the doctors leave the room, because they don’t want to be exposed to it all day. Most of the time, x-rays interact with atoms by pushing electrons from a lower shell to a higher shell (let’s call them orbitals from now on). For this to happen, the atom must possess these higher electron orbitals and the incoming photon must match exactly the energy gap between the orbitals.
Here comes the catch: Most atoms in our body (carbon, hydrogen, oxygen, nitrogen) are so small, that the energy of the x-rays photons is way too high to push any electrons around. This is different for atoms in our bones. We find a lot of calcium there. Still not a huge atom, but much bigger than most others and at really large concentration in our bones. Calcium can easily absorb an x-ray photon, so it can’t end up on the detector screen anymore.
Another sort of interaction is scattering of the x-rays. They are not absorbed in that case, but sent off in a different direction, which would most likely also not hit the detection screen. Also, this is more likely for electron-rich atoms like calcium, and less likely for atoms found in soft tissue.
X-rays can lead to DNA mutations
Any why are they dangerous? Sometimes, with really low probability, they take an electron from one of the smaller atoms, and knock them out of the molecule entirely. This molecule is then missing an electron and it is not happy with that. It is looking for a new partner to make a chemical bond with, because it needs to find someone for the now single electron from that pair that it was previous in (electrons in atoms or molecules are (almost) always paired). So the electron goes on quantum Tinder and looks for a new partner to bond with. If this new partner happens to be an atom in your DNA, you will get a modification that can lead to a mutation if it is not being repaired properly. And this mutation can carry an increased risk for cancer. Or the cell just dies. It is okay if it happens here and there, but at too high exposure to radiation, you will get quite sick.
Of course, many unlikely things have to come together here: An x-ray knocking an electron out of a small atom, that atom being in your DNA, the mutation not being repaired, the mutation carrying a cancer-risk (or the cell dying), the cell actually developing cancer and not being killed before. But with the high dose of x-rays and huge number of DNA atoms in your body, it is still not impossible, only improbable.
Making x-rays is surprisingly easy
Next question: How do we make x-radiation? To me, as a trained biochemist, the generation of any kind of specific radiation is not very intuitive. I suppose you reading this feel the same way. So let me tell you how scientists make x-rays. The general principle in a small hospital device is: Fire electrons against a piece of metal, usually tungsten (the stuff in good ol’ light bulbs) in a vacuum chamber. The electrons interact with the metal atoms two ways: Either, it knocks an inner electron out of the atom, resulting in an electron from a higher orbital to fall down and fill the hole, while it releases a photon carrying the energy difference (in the x-ray range).
On the other way, the electron’s path is curved by the electric field of an atom’s nucleus, resulting in deceleration. At the same time, the electron loses energy, again in the form of a photon (physics teaches us, that energy must be preserved. You remember that from high school, right? Here it is again). This is called Bremsstrahlung, a German word, literally meaning braking radiation, and the term is used just like that in English. For me, as a German native speaker, it is quite amusing, that English scientists use such a peculiar and rather specific German word. Due to both effects, we get x-radiation, that we can send through a filter and into the patient. On the other side of the patient, we then measure how much x-rays intensity per pixel we see. And there is our image.
There is another way to utilize Bremsstrahlung, and this is in a particle accelerator. There, electrons are accelerated on a ring, several hundred meters in circumference. A system of magnets decelerates the electrons, resulting in high-quality radiation. This is called synchrotron radiation. It is the Ferrari among radiation, and scientists go nuts for it. They can tune it over almost the entire electromagnetic spectrum (microwaves to x-rays), create them in high intensity and so on. Perfect for scientific experiments. However, they require a particle accelerator. Not quite the type of the Large Hadron Collider at CERN, but still pretty big machines. Pretty famous in Europe are ESRF in Grenoble, or DESY in Hamburg. This is of course not practical for routine use in a hospital (you also wouldn’t want to expose a patient to this kind of radiation).
Replace the patient with a crystal, get a molecular structure
We can use the diffraction of x-rays on molecules, to get information about their structure. It must be X-radiation here, because it is being scattered of the electrons itself, which define the structure, the bonding situation and position of the atoms. A different kind of radiation would not have the same effect. But more about that another time.
When we do this kind of experiment, we call it x-ray crystallography. So basically, looking at crystals with x-rays. A crystal is a perfectly repetitive pattern of the same unit cell. If we manage to crystallize a molecule, it means that all the molecules are in the same orientation in the entire crystal. This works with small molecules, like a drug, up to large biomolecules, like proteins. The x-rays are being diffracted by the electrons in the crystal lettuce… sorry, lattice (Damn you, German accent) and interact with other x-rays that are also being diffracted. This leads to local spots of constructive and destructive interference that we can catch with a detector behind the crystal. Much like in the hospital, just here we don’t get a picture of your bones, but a so-called diffraction pattern.
What happens then is awfully complicated and I can’t possibly explain it in simple word (read: I don’t fully understand it myself. Honesty always wins. Keywords for the curious: Bragg’s law, reciprocal space, Fourier transformation).
After a lot of math magic, we end up with the electron density in the 3D space. This is basically knowing what the molecule looks like. We then model in a molecule that fits best into the electron density data, and there we go. Through bombarding a crystal with x-radiation, we now know what molecules it is made of. How else would you do that? (Note: There are other ways, of course, and I find them even more beautiful, but I will talk about this another day). This is actually not new. X-ray crystallography has been done for over 100 years now, and was a major breakthrough at the time. Back then, determining the structure of even a small molecule was… a major pain in the ***. But thanks to synchrotron radiation and fast computers, this technique became a standard method for many chemists and related life scientists.
I find it amazing how we can specifically produce this peculiar form of radiation, and how we found so many different applications for it. This was only two important ones in life sciences, but there are so many more, of course. Astronomy, airport security and whatnot. We find even more in chemistry, like x-ray fluorescence to determine the elemental composition of a sample (Calm down biologists, it has nothing to do with microscopy. It is only the same quantum-mechanical principle), or x-ray microscopy for very small structures (here you have it, biologists <3 ). Buuuuut, there are many more interesting methods in life science and medicine, both to image a patient and to determine a molecules structure. One of them is magnetic resonance, that we use in MRI. Truly, a wonderful technique. Come back some time to read more about those.
Special thanks to Carol and Leo for keeping me company in the hospital.
Musical inspiration: Gravity, because that’s what I was listening to when I fell off my bike, and ultimately it was gravity bringing me down. Beware the heavy tunes. Alternative in case of non-appreciation: In my time of need.