Nanoscale MRI: Medicine's next big thing?


BACKGROUND:    Magnetic Resonance Imaging (MRI) is a test that uses a magnetic field and pulses of radio wave energy to make pictures of organs and structures inside the body.  The MRI shows problems that other imaging methods cannot detect and it also gives different information about structures in the body than can be seen with an ultrasound, X-ray, or a CT scan.  The area of the body being examined has to be placed inside a special machine that contains a strong magnet for an MRI test.  The pictures taken by the MRI scan are digital images that can be saved and stored on a computer.  They can also be viewed remotely, like in a clinic or an operating room.  MRI is done for many reasons.  It can be used to find bleeding, tumors, injury, blood vessel diseases, or infection.  (Source: www.webmd.com)


HOW IT IS DONE:  The patient will have to remove all metal objects and clothing.  The patient will have to lie on their back on a table.  The table will slide into the space that contains the magnet.  A coil device may be placed over or wrapped around the area to be scanned.  The patient has to be completely still while the images are being taken.  An MRI test usually takes 30 to 60 minutes; however, it can last up to two hours.  (Source: www.webmd.com)


RISKS:  There are not any harmful effects from the magnetic field used for MRI, but it is very powerful.  It can affect pacemakers, artificial limbs, and other medical devices that contain iron.  The magnet can even stop a watch if it is too close to it.  Loose metal has the risk of causing damage or injury if it gets pulled toward the magnet.  Metal parts in the eyes can damage the retina.  Iron pigments in tattoos can cause eye and skin irritation.  Some medication patches can cause a burn.  Also, a slight risk of an allergic reaction if contrast material is used during the MRI is possible.   (Source: www.webmd.com)


NEW TECHNOLOGY:  MRI can reveal details of living tissues, organs, and tumors.  The nanoscale MRI can see all the way to the level of atoms.  Doctors believe this could make visual diagnoses of a person's molecules, examine damage on a strand of DNA, watch molecules misfold, and identify a cancer cell by the proteins.  Doctors at The City College of New York used tiny defects in diamonds to sense the magnetic resonance of molecules.  A standard MRI gets a resolution of 100 microns, that is about the width of a human hair.  It can go all the way down to 10 microns, the width of a few blood cells.  The nanoscale MRI would have a resolution 1,000 to 10,000 times better.  Diamonds are crystals made up almost entirely of carbon atoms.  When a nitrogen atom lodges next to a spot where a carbon atom is missing, however, it creates a defect known as nitrogen-vacancy center.  "These imperfections turn out to have a spin, like a little compass, and have some remarkable properties," Carlos Meriles, PhD, was quoted as saying.  Researchers realized that these NV centers could be used as very sensitive sensors.  For example, they can pick up the magnetic resonance of nearby atoms in a cell.  The NVs shine when a light is directed at them, unlike the atoms in a cell.  If you illuminate green light it will flash back red.  "It is a form of what is called optically detected magnetic resonance sends back flashes to say it is alive and well.  The NV can also be thought of as an atomic magnet. You can manipulate the spin of that atomic magnet just like you do with MRI by applying a radio frequency or radio pulses.  Ultimately, one will use a nitrogen-vacancy mounted on the tip of an atomic force microscope, or an array of NVs distributed on the diamond surface, to allow a scanning view of a cell, for example, to probe nuclear spins with a resolution down to a nanometer or perhaps better," Carlos Meriles, PhD, explained. (Source: http://www.ccny.cuny.edu/news/mri-for-nanoscale.cfm)



Carlos Meriles, PhD, Professor of Physics at The City College of New York, talks about improving MRIs. 

Can you explain the problem with the regular MRI?

Dr. Meriles: The main problem boils down to the technical word "sensitivity." It means the amount of material you need in order to get a decent signal, a signal that one can measure in a reasonable amount of time. One can think of atoms as little magnets that one can somehow orient with a magnetic field. The stronger the magnetic field, the larger the fraction of atoms that the magnet orients. Even for the strongest MRI magnets, however, the fraction of oriented atoms is relatively small. Therefore, the minimum amount of sample per image pixel required to produce a signal is comparatively large, which translates in a relatively poor spatial resolution

So, right now the MRIs we get in the hospitals just don't have a high enough resolution?

Dr. Meriles: That is correct. The resolution is precisely tied to sensitivity because resolution means how small the pixels of an image can be. The more resolution you have, the smaller the pixel size is. That effectively means that the sample size per pixel decreases. If the sensitivity is not good, if within a pixel only small fractions of atoms are contributing, then it means that there is a smaller signal and the result is a noisier image. The standard protocol for detecting a magnetic resonance signal in an MRI machine is using coils. It turns out that the aligned atoms in a sample, we call them spins, behave in some peculiar way. The spins will, after you excite them with radio frequency, respond and they'll generate a radio frequency signal that you'll pick up as if using a radio. You go with a radio antenna , put it close to the sample that you want to detect, and that's how you get a signal. The minimum number of spins that you need in order to get a decent radio frequency signal back from the example that you're exciting is comparatively large, and so the sample size that you can have (and ultimately the resolution if one fractions the sample into smaller and smaller pieces) is limited. A typical MRI amounts to somewhere close to one hundred microns (a hundred microns is a tenth of a millimeter).

Where do you want to take it to?

Dr. Meriles: Imagine that you want to do exactly the same you do in a standard MRI. We've all seen these very nice images where we can distinguish different parts of the brain. Imagine you want to see systems that are perhaps as complex as the brain but much smaller at the micron scale or sub-micron scale. So you want to see, for example, the workings of a molecule in the membrane of a cell. That kind of limit you can't even think of reaching with standard MRI technology. We need to come up with other ways of moving sensitivity and resolution forward.

How are you doing that?

Dr. Meriles: Well, you have to look back probably fifteen, maybe twenty years. People came up with strategies other than the one that we are pursuing right now, and perhaps the more powerful strategy is called magnetic resonance force microscopy. It's a technique that works with other principles and it doesn't use a coil, just a small permanent magnet attached to what is called a cantilever. This is the working geometry that is typically used in an atomic force microscope. The idea was to somehow integrate magnetic resonance with atomic force and in that way have the resolution that is associated with this type of microscopy.

The atomic force microscope, is that what we see over there?

Dr. Meriles: Yes, we want to somehow recycle those same ideas in ways that we can now use with a new approach that exploits the properties of the so-called nitrogen vacancy centers in diamond. Let me just say in a few words what that is. First of all, imagine a diamond crystal. So, a crystal is an array of atoms that is near to perfect. It turns out that crystals do have imperfections. For example, a diamond crystal is a lattice of carbon atoms and sometimes in this ideal lattice there is one atom that is replaced by another one, that's called a substitutional impurity. Nitrogen instead of carbon can be the impurity. There are some other impurities possible and these impurities, by the way, are the ones that give the fancy colors to diamonds. For example, if you have yellowish diamonds then there are nitrogen impurities and if you have bluish diamonds it'll have boron, and this is the reason why these impurities are sometimes called color centers. Now there's one particular impurity that we are interested in in this particular work which combines a nitrogen atom with an empty site (or 'vacancy') adjacent to it. We call this combination a nitrogen vacancy center. It turns out that the nitrogen vacancy center has become a hot topic and in physics it's becoming more and trendier because people have found that these NV centers have very peculiar properties. Remember when we were talking before in terms of the fraction of spins that become polarized with a strong magnet? Well, in this particular defect, if you shine the NV center with green light (just a millionth of a second long pulse should be sufficient) the spin polarizes to almost a hundred percent. It's as if you have brought an infinitely large magnet and put it close to it. Of course that is, in practice, impossible. You can accomplish that with just a microsecond long light pulse.

What does that do?

Dr. Meriles: There's one more ingredient that plays an important role. The NV fluorescence (or light that the NV center emits upon illumination) depends on the initial spin state. If the NV spin is pointing up, then the fluorescence will be brighter. If it is pointing down, the fluorescence will be dimmer. So we say we can 'optically detect' the NV spin state. This is important because it allows us to detect up to single NVs, something impossible if one was to use a coil, as in standard MRI. It is important to keep in mind that, in general, other spin systems do not behave this way and that as a result; they cannot be looked at with the same sensitivity. So imagine one set up a geometry that allows one to bring the NV in close proximity with the part of a sample system one wants to investigate, say a cell. The NV spin will serve as a sort of probe to report what's going on around it. If, the NV sees nuclear spins around it behaving in some particular way, one can come up with clever schemes to encode in the NV center information that one wants to know about these other spins. Then one can use light to read from the NV spin information about this other spin system that one cannot see directly.

It takes you down from being able to see the image of the brain too?

Dr. Meriles: It takes you down only a couple of atoms in the NV vicinity.

How many times stronger is it?

Dr. Meriles: For practical purposes we can say a thousand times stronger roughly. So imagine that with present technology and assuming that you do not go with the systems that you find in a hospital where the resolution, as I said, could be something on the order of a hundred microns. Imagine that you do some laboratory work, and people have done this, and you push down the resolution so you can go to something live five microns, which are five thousands of a millimeter. With an NV center and this is actually what was demonstrated in this last work, you can go up to one thousand times higher resolution, that is, something in the order of nanometers.

Everybody is worried about getting MRI's all the time. Is the stronger MRI going to be more dangerous?

Dr. Meriles: That's actually a good question and a nice way to look at it. Remember the way that I said the NV was going to get polarized? We used light pulses, and that essentially means that a strong magnet in that particular case is unnecessary. Essentially your MRI is going to take place with a very small magnetic field, and actually, in the experiments that we run in the laboratory we just use a small permanent magnet (like the one that one would put on the door of a fridge) to do the experiments. So, the bulky magnets typical of MRI you won't need anymore; it's a completely different ballgame because now the structure and the working geometry resemble a microscope much more than they resemble the standard MRI system.

Is it safer and more powerful now?

Dr. Meriles: Yes, we could say so. Of course, the kind of applications that you're going to be able to do with such a system are different, and so it's not thought of as a system for investigating humans directly the way we do it in MRI.

Will this replace the MRI we see in the hospital?

Dr. Meriles:  This most likely won't replace it. It's just opening up other possibilities.

Why wouldn't it replace MRI if you can see more?

Dr. Meriles:  It's not impossible to conceive extensions that will eventually complement MRI as we know it today, and people are working in that direction too. Say you could put diamond nano-crystals inside the part of the body that you want to look at, or some other system that you can inject in your blood and use it to generate large alignments of the atoms or spins in this part of your body. In that case the strong magnets won't be necessary and it will be safer.

What would you use this for?

Dr. Meriles: What I'm particularly interested in is in what happens at the nano-scale; that is my main driving interest.

You can do this with an atomic microscope, right?

Dr. Meriles: Yes, that's right. What we've discussed so far, and that's because perhaps it's more familiar to everybody, are these applications in biology or biomedicine. Now, people are thinking in a different way where you now start thinking of these spins or little atomic magnets as units of logic the same way you have now electronics working with zeros and ones. The zeros and ones mean having or not having a charge at a certain position in a circuit, but it turns out that you could actually start thinking of replacing that kind of logic, an electronic-based logic or charge- based logic, into a spin-based logic where now you have spins pointing up or pointing down indicating zeros and ones. There are a number of advantages in going in that direction. One in particular is the fact that the amount of heat that one creates by changing the orientation of these spins is comparatively smaller than replacing a charge or taking it away. So as circuits become more and more dense, the heat that one dissipates becomes a serious problem, and people are trying to go around those problems and spins are an interesting alternative to explore. This new form of electronics by the way is called spintronics and is an area that is taking off as we speak. Spintronics is already part of present technology, you'll find it in certain hard drives and the replacement is not complete yet, but I think that it's evolving in that direction. However, there is something that is perhaps more mysterious or esoteric and that you won't hear too much out there. Within the physics community there's a large group of people working intensively on what is a new form of logic. Imagine that I tell you that you have a system that can be in state zero or state one or any combination thereof simultaneously. So the possibilities of processing information with such a system turn out to increase dramatically in certain cases. This form of computation exploits some quantum properties that you only find when you deal with very microscopic systems such as individual's NVs. There is now the idea that you will be replacing what we call classical logic zeros and ones with this new form of computation which is called quantum computation or quantum information processing, which will be way more efficient than what is presently possible. NV centers in particular turn out to be very strong candidates for these kinds of applications precisely because one can manipulate the spin state in such a controllable way which allows one to do things that you simply can't do in other systems. This is what makes them so special.



Carlos A. Meriles, PhD

Professor of Physics

The City College of New York – CUNY

(212) 650-5625