BENG 100: Frontiers of Biomedical Engineering

Lecture 21

 - Bioimaging (cont.)


Professor Saltzman continues his discussion of biomedical imaging technology. Magnetic resonance imaging (MRI) is introduced as an alternate form of imaging, which does not use ionizing radiation yet can provide detailed structure of the body. Functional MRI (fMRI) has a different application from traditional MRI. It can be used to measure oxygen consumption (tissue metabolic rate), and is an important tool in deciphering brain function. Third, ultrasound imaging is another imaging technique that can detect motion by translating sound wave reflections into structural images at fast timescale. Finally, examples of nuclear imaging and advances in light microscopy are discussed.

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Frontiers of Biomedical Engineering

BENG 100 - Lecture 21 - Bioimaging (cont.)

Chapter 1. Introduction [00:00:00]

Professor Mark Saltzman: So, today we’re going to continue talking about imaging. Last Tuesday–on Tuesday I talked mainly about imaging using X-rays and the conventional sorts of X-ray which a chest X-ray which leads to a projected image. So, you understand the limitations of projected images, and from X-rays something about the physics of how an X-ray image is formed based on X-rays passing through your body. Depending on what tissues, what types of tissues the X-ray passes through, some of that X-ray energy will be absorbed. Therefore, only a fraction of it is available to pass all the way through your body and expose the X-ray film.

We’re going to talk about several alternate forms of imaging today, many of which are similar to CT imaging. Now, CT imaging is a special form of X-ray imaging where you rotate the source of X-rays and the detector around the object you’re trying to image around the patient. You take images at a large number of angles and using mathematical approaches you reconstruct the three dimensional image from those multiple two dimensional projections. That mathematical process is called reconstruction from back projections and it results in a three dimensional image, in a CT a slice of the object of the patient is obtained by rotating the source in the detector around that axial location.

What we’re going to start with is talking about an alternate to CT–we’re going to talk about an alternate to CT which forms the same kind of images. That is, images of an axial location, maybe a transverse image; a slice from the body will be imaged using a technique called magnetic resonance as an alternative to using X-rays. We talked last time about one of the problems with X-rays, that X-rays had a lot of beneficial qualities for making images. They pass through tissues, they allow you to look inside, they’re absorbed selectively by tissues of different density, they’re able to expose X-ray film, and all of those properties make them very good for forming images. The problem is that X-rays–X-ray radiation is a form of ionizing radiation that can cause damage to cells and tissues in the body. One has to be careful about how much dose you expose a particular patient to.

Chapter 2. Magnetic Resonance Imaging [00:05:04]

In magnetic resonance imaging, you use magnetic fields and radio frequency radiation, non-ionizing forms of radiation in order to form an image. The kind of image you form is the same. You form a three dimensional image of objects, but since the physics is different, the things that create contrast or your ability to see one object from another in an MR image are different than in a CT image. In a CT image, what forms the contrast is the absorbance of X-rays by the tissue. So, your lungs, which are mostly air, allow X-rays to pass through relatively easily. They’re different from soft tissue like blood or the muscle tissue of your heart which absorbs some of those X-rays, and they’re different from bone, which absorb a lot of those X-rays. It’s density of the tissue, absorbance of the X-rays that leads to contrast.

One of the things I didn’t talk about last time was that sometimes physicians, when they want to images of objects where there’s not a lot of intrinsic contrast–like, say, you want to look at the intestine, but if you take an X-ray of the abdomen everything appears like soft tissue, everything looks about the same. If you, however, fill up the intestines with air by feeding air to the patient or by somehow getting air into the intestinal tract, then that image will appear dark where that air is. You can create contrast, you can see what’s inside of the intestine that way. Another way you can do it is by having the patient drink something that absorbs X-rays very readily and that something is usually a solution of barium, a colloidal barium solution that’s very X-ray dense. So, you can create contrast that way; a digression, something I didn’t mention last time and it is mentioned in the chapter.

What I want to talk about MR is different way of forming images, uses a different kind of physics, and so the elements of intrinsic contrast are different. We’ll talk about what makes MR images in a few moments. Bone does not appear well on MR images, whereas, bone appeared very well in X-rays and CT’s for example. If you’ve taken chemistry, some chemistry in college or in high school, you’ve probably heard of NMR, nuclear magnetic resonance. It was discovered by chemists as a way of analyzing chemical samples. It turns out that if you put certain nuclei, if you put certain atoms in a magnetic field, some of them will align with the magnetic field because they have a magnetic dipole; atoms have a magnetic dipole. Hydrogen atoms or protons have an odd number of nuclei, of neutrons or protons. Because of that they have a dipole, a magnetic dipole. You put them in a magnetic field, they will align with that magnetic field. If you then perturb the molecules that are aligned with the magnetic field using radio frequency waves or other magnetic fields, we’ll talk about this in a moment, then you can measure something about the properties of the atom.

Chemists use this, because it turns out that if you align all the hydrogen atoms or protons in a sample, if you align them in a magnetic field and then you stimulate them with the right kind of radio frequency, they will respond by producing a radio frequency of their own, by producing an energy emission of their own. That energy emission is at radio frequency wavelengths and you can detect it. Protons that are in different environments will respond slightly differently. A proton that is–or a hydrogen–I’m going to say proton instead of hydrogen atom because that’s easier to say, or hydrogen ion, a proton that’s in a fatty solution will behave differently when stimulated in a magnetic field than one that’s in water. One that’s in bone will behave even differently than that. The properties that you can measure by this process called nuclear magnetic resonance depend not only on the atom that you’re stimulating, hydrogen in this case, but the microenvironment or local surrounding that the atom finds itself in.

If you talked about this in chemistry, you might talk about distinguishing different hydrogen ions that are associated with an alcohol molecule or with a benzene ring, and how ones that are in different positions on the molecule will actually respond differently, give you what chemists call different chemical shifts. It’s that same phenomenon that’s being used here to create images. It was discovered in 1946 that atomic nuclei could absorb and reemit radio frequency energy, and particularly, when they were aligned in a magnetic field. That led this discovery of the nuclear magnetic resonance concept; led to the Nobel Prize in Physics in 1952. It’s called nuclear magnetic resonance because it involves–it depends on the particular properties of the nuclei of atoms, that is the number or protons, the number or neutrons. It’s magnetic, because a magnetic field is required in order to align the ions. It’s called resonance because you’re looking for a resonance between the excitation of these molecules, these aligned molecules, aligned in a magnetic field which are exciting them with radio frequency waves. You’re looking for a particular resonance between the magnetic field that’s applied and the stimulation that you give with radio frequency.

Now, when I was introducing the subject, I didn’t call it nuclear magnetic resonance imaging, I called it magnetic resonance imaging or MRI. That’s the common name that’s used for making medical images using this particular physical approach. Why do you think the name was changed from nuclear magnetic resonance to MRI during the 1980s when this technique started to be used in people? Anything with nuclear doesn’t sound so good. You don’t want anything with nuclear done to you, probably because of other uses of nuclei and concerns about nuclear sources of energy and that kind of thing, so the name was changed. I don’t want you to be confused because the phenomenon is the same.

To perform magnetic resonance and to make magnetic resonance images you need a very strong magnetic field. Magnetic fields, if you remember from physics, are measured in a unit called Tesla. Most of the clinical units that are used to perform magnetic resonance images have magnetic fields ranging from 1.5 to 4.0 Tesla. A Tesla, another unit for that is the Gauss and the conversion factor shown here. Just to put it in perspective, you know that the Earth has a magnetic field, that’s why compasses work; has a magnetic field. If you have a compass which is just a device that detects the Earth’s magnetic field always aligns with North, for example. The magnetic field of the Earth is about .3 Gauss or–and it ranges between .3 and .6 so a Gauss is a–that would convert to–.6 Gauss converts to 60 micro-Tesla. So 60 x 10-6 Tesla is the magnetic field of the Earth, we’re talking about much, much higher magnetic fields than that.

You’ll need to know this because you’re going to go down and visit the MR research center at Yale this afternoon. Magnetic fields of this strength can interact with other magnetic objects like credit cards that you might have in your pockets, or keys that you have in your pockets. So when you enter an MR suite, you have to make sure that you’re not carrying anything metal, wearing anything metal, or carrying anything magnetized that has a risk of being demagnetized with it because these are very strong magnetic fields. Because of this the MR facility that you will see here at Yale is in the basement of The Anlyan Center and usually these machines are in the basement.

If you got to a hospital and you have an MR taken; usually you go down to the basement. Why is that? Because they’re put in rooms that are specially shielded, they’re specially shielded so that the magnetic fields cannot penetrate outside of the room. That’s so that people that are walking by on the street don’t have their credit cards erased. People that are walking by on the street don’t have metal objects pulled out of their hands by the strong magnetic fields. This is one of the risks for people that work around nuclear magnetic resonance imaging, is that the fields are so strong that any metal object that’s in the vicinity of the magnetic can be become a projectile. They’re very cautious about metal, another reason why we asked you not to take any stuff that’s unnecessary with you when you go down to The Anlyan Center this afternoon. The magnetic fields are very strong.

Anybody had an MR image taken? Wilma, several of you; it was a device, it might not have looked exactly like this but looked something like this. This looks similar to the CAT scanner I showed you last time, in that there is an instrument with a–basically a big cylinder with a cylindrical hole in the middle. This hole, this is where the patient is going to go, the patient will be lying on this cart, and this will act like a conveyor belt that will move the patient inside the cylinder.

It’s close-fitting, you don’t want the size of the cylinder to be too far away from the patient because you want the magnetic field forces and the radio waves that are emitted by the ions in your–by the atoms in your body to be very close to the detectors that are measuring it. Because of this, when you’re inside, many people–Wilma did you experience this? You feel claustrophobic when you’re inside the machine because you’re in a very confined space and the images take some time to acquire. The quality of the image depends on the strength of the magnetic field and how long you acquire the image. If you have more time to wait you can get a better image, and so there’s a tradeoff between building magnets that are incredibly strong, which is very expensive and time for the patient to be inside the instrument to acquire an image that has a high quality.

Surrounding this cylinder are coils and coils, many miles of coils of wire, and electrical field. Electricity passes through these wires in order to create a big electromagnet and large magnetic fields within this machine. Now, the other thing about the machine is that the operator can control the strength of the magnetic fields, it can control stimulation of the object with radio frequency waves, and it can control what radio frequency signals it picks up from the object as well. One of the advantages of MR, and we’ll see a little bit more about this as we go through the physics, is that it can be tuned. You can tune the imaging method in order to look at the kinds of things that you would like to look at. That turns out to be one of the powerful things about MR. People are still discovering new ways to look at the resonance between the magnetic field and its affect on atoms and the radio frequencies that are generated, to learn how make new kinds of images. We’ll talk about some of that as we go.

The magnetic resonance that’s most done in people for clinical imaging takes advantage of the fact that our bodies are largely water. All those water molecules have hydrogen atoms associated with them. There’s a lot of hydrogen in your body, and hydrogen atoms are susceptible to magnetic resonance because they contain this dipole moment that will align in a magnetic field. What happens in magnetic resonance is you’re placed in a very large magnetic field.

Many of the hydrogen nuclei in the molecules within your body align with this magnetic field, and then the machine sort of tips those aligned molecules out of alignment. If that’s done properly, you will start a kind of motion in these molecules, what’s called a procession, where the molecules move like a top. When they are performing this kind of motion within the magnetic field, they’re trying to get back to the preferred alignment but they’re doing that in this top-like fashion. If you have many, many atoms that are all processing in the right way they will emit radio frequency waves that you can detect in this cylinder outside.

This shows it sort of schematically. You have atoms inside your body, these are hydrogen atoms, for example. You place the body within a strong magnetic field, and these atoms align so that they are parallel with the magnetic field, which is going from top to bottom here. You stimulate these atoms with radio frequency waves and you knock them out of alignment. Now, you can’t just stimulate them with any radio frequency wave, that radio frequency wave has to be exactly right for the atoms that you want to move. It has to be radio waves that are at the correct frequency or wavelength to stimulate these particular atoms. That’s one of the things that makes MR so versatile, in that if you stimulate them with one frequency, you can manipulate hydrogen atoms. If you stimulate them with another frequency, you can stimulate other atoms.

Now, the reason why most of the images you’ll see are based on protons or hydrogen nuclei is because hydrogen is so much more abundant than everything else in your body, and so you get a good signal with that. If you were stimulating other kinds of atoms, you wouldn’t get as strong a signal, you wouldn’t be able to make as good an image. You stimulate these atoms with a radio frequency, they begin this motion or this procession, and this just shows schematically that this procession is like a top. They’re out of alignment, the nuclei are rotating. They’re eventually coming back to their equilibrium position which would be aligned with the magnet again. What you measure in the MR device is this relaxation from the excited or tipped position, relaxing back to their equilibrium or aligned position.

Now, if you go on–if any of you go on to study quantum mechanics or you try to study the physics of medical imaging, particularly MR in more detail, you’ll learn that this simple description I gave you is not entirely accurate. It’s not inaccurate, but it doesn’t describe the whole thing. It’s really a quantum mechanics phenomenon that’s happening with the molecules here. It can’t be described completely unless you have the sort of tools of quantum physics to describe it, but this is a sufficient way of thinking about what’s going on in here.

What you measure, then, is the relaxation of these excited molecules back to their aligned state. You can measure that because as these molecules are processing they’re emitting radio frequency radiation which you can detect. Now, this involves magnetic fields, strong magnetic fields. It involves radio frequency radiation, the kind of radiation that radio stations use to broadcast signals that are picked up by antennas. These are generally presumed to be safe for biological tissues. There’s no ill effects that we know of, of exposure to magnetic fields or radio frequency radiation at these wavelengths. So, it doesn’t have the same concerns that X-ray radiation or other kinds of radiation, which I’ll talk about in a few minutes, have.

This is some examples of MR images. These are MR images that are taken at different locations in the brain. Remember, now, that the patient is being conveyed on this table into the core of the instrument and measurements are made only on the part of the body that’s inside the instrument. Just like in CT image, you move the patient through and you take images of different slices through the patient. Now, if the patient is having a brain or head MR scan, you would just put them in until you went through this part of the body. If you’re doing it in the abdomen or the leg, you would just scan that part of the body. This shows, then, images, transverse images at various locations moving down. This is near the top of the head, this a little further down, you can see the ventricles.

I think actually these two images might be from the same location, but they show you one of the features of MR. That is, by looking at different relaxations or stimulating with different pulses of radio frequency, you can see different kinds of contrast. In this image you can see more clearly the distinction between gray matter and white matter. In this image you don’t see that so clearly but you see better the distinction between brain tissue and the cerebral spinal fluid that’s in the ventricles. The point is that the technique can be tuned to see what you would like to see best. Then, going farther down in the brain you see–now you’re seeing some of the bones of the face and the cerebellum back here, or a lower section of the brain. So, this is a section probably from somewhere in here and this is even lower down than that. These are just examples of some magnetic resonance images.

As I mentioned, magnetic resonance is not so good at looking at bone because bone doesn’t have a lot of water in it. Doesn’t have a lot of–so it doesn’t contribute a lot of signal but it’s very good for looking at differences between soft tissues. Remember in CT soft tissues like the muscular wall of the heart and the blood that’s inside the heart look roughly the same. You can’t distinguish those well, there’s not intrinsic contrast. With MR there is intrinsic contrast because those–the properties of those different tissues are different by this method.

Chapter 3. fMRI [00:25:13]

A newer form of magnetic resonance imaging is called functional MR imaging and it uses the same machine. It uses the same approach, but instead of designing your radio frequency pulses so that you look at the static structure, you design it so that you’re particularly sensitive for looking at flowing blood. You can actually measure the velocity of blood flow in different regions of the brain. Now, you can do that because blood contains a lot of water. This is water that’s not static, just staying in one place in the brain, but it’s moving through blood vessels. You can detect the motion of the blood vessels with this technique.

It can also tell the difference between saturated and desaturated blood. What’s saturated blood? Here, I mean blood that’s saturated with oxygen, so it’s loaded up with oxygen; desaturated blood is blood that’s had the oxygen removed. Now, if you can measure blood flow and you can measure differences between saturated and desaturated blood, that means that you can monitor within a small region of tissue how much blood flow is going through, how much oxygen is being consumed. You can measure, locally, what’s the rate of oxygen consumption in a tissue.

Now, if you know oxygen consumption, then you know something about metabolic activity in that tissue. A region of tissue that’s consuming a lot of oxygen is doing a lot of work. In the brain, if you find regions of tissue that are consuming oxygen, that means those are regions of tissue where there’s a lot of energy being consumed, those are regions of tissue where there’s a lot of neural activity, a lot of brain cells doing what brain cells do. It’s called functional MR imaging because through this approach, one can look inside the brain, for example, and find regions that are performing functions.

An experiment that–well, the other thing about fMRI before I talk about the experiment, is that instead of just looking at anatomy now, this is a high resolution picture of the anatomy of the brain, an fMRI image is fuzzier. You don’t have as high a resolution and that’s because you want to take images fast, you don’t want to wait a long time. You want to be–you want to see how the image changes with time. In a static image, when they took a picture of Wilma for example, they kept her inside the machine for a while so that they could get a really high resolution image of the structure in her brain. She was asked to remain very still because you don’t want to have any motion, you want just a picture of the static’s. In fMRI, you want to take a picture faster but then you want to look at how it changes with time because it’s these changes in time that allow you to look at things like oxygen consumption. You have to look over time in order to measure that.

In an fMRI–in one kind of fMRI imaging you look at blood oxygen level, that’s a measure of neural activity, when blood oxygen goes up neural activity goes up, the extraction of oxygen goes up and the fMRI signal goes up. Here’s an example of an fMRI image, and actually the fMRI image isn’t shown here. The fMRI image would be a blurry one like the one I showed you in the last slide. You might find regions where there’s high levels of activity, and you would superimpose those on a static image of that same brain, so here two kinds of imaging were done. One was the high resolution MR imaging to get a picture of the anatomy, and then this more rapid time sequence of images to find out where oxygen consumption was occurring.

What was discovered was that oxygen consumption is occurring in this location here and this location here. This is known to be a certain area of the brain called Broca’s area that’s involved in speech. I don’t remember whether it’s in hearing and decoding speech or in producing speech, I think it’s in hearing and decoding speech but I don’t remember. In this particular example mixed speech was–while the patient was being imaged they were being exposed to speech that included a mixture of languages, both Spanish and English. In this picture they were only listening to Spanish, in this picture they were only listening to English. What you see is that when the mixed–under the mixed condition, when they’re hearing both Spanish and English, there’s a certain portion of the brain that’s more active than it is with only Spanish and only English. From this you can conclude that this part of the brain must be involved, somehow, in the special activity that was happening at this point here. That is some kind of mixed language experience.

Many, many–this as you could extrapolate from this, and you could imagine that this approach where you could look at what areas of the brain become active during sorts of activities, certain sorts of behavior, when certain emotions are elicited, has become a very powerful tool in psychology. You can do psychological experiments while patients are getting fMRI scans, and you can find out what parts of the brain are involved in that kind of psychological response. This imaging is teaching us a lot more than just what is the normal structure of tissue, in this case the brain looks like, but how does it really work in a functioning animal like a person.

That’s a very brief introduction to MR imaging, there’s a lot more to learn about this, you’ll learn more about this, and you’ll see some of these instruments this afternoon. There’s more detail in the book as well.

Chapter 4. Ultrasound Imaging [00:31:33]

A second kind of imaging which shares an advantage with MR in that it does not involve ionizing radiation is ultrasound imaging. Ultrasound imaging is different from the others we’ve talked about in that there is no electromagnetic radiation involved. You’re not using light or different forms of light; you’re using sound to create images instead. Sounds is pressure waves that transmit through a medium. When I’m talking up here my vocal apparatus is creating waves of pressure in the air which get transmitted through the room. You can understand them because the waves of pressure that I’m creating stimulate your eardrums at the right frequencies and you convert that into sound.

Ultrasound uses much, much higher frequencies of sound than our ears can detect. We detect, I forget exactly what the range is, but up to I think 40,000 Hz or cycles per second is the frequency and this is in the megaHertz range or millions of Hertz range, so it’s higher frequency sounds than you can hear. Some have very short–of these high frequency sound waves have very short wavelengths. They can penetrate through tissues. Ultrasound allows for good imaging of anatomical structure. It’s also a fast imaging method, and so it can allow you to look at motion in ways that are difficult to do using some of these other techniques, and I’ll tell you about that.

The way that ultrasound works is you have to get sound waves propagated into the body and you do that through a special device called an ultrasound transducer. The transducer is placed right on the surface of your body. It might look like a cylinder like a probe that’s placed against the surface of your body. Usually not even just placed against a surface of your body, but it’s placed with some kind of a gel, a liquid gel such that the probe comes in very good contact with your skin. That’s because sound waves don’t transmit very easily across interfaces. If I put something up between my voice and you, then the sound waves don’t transmit as well, you can’t hear it. Sound waves bounce off interfaces. You want to get the sound to go into the skin, you have to put the transducer, which is producing the sound waves, right up against the skin. You don’t want a gap of air in between and that’s why you put the gel.

Now, this transducer has a special material in it that’s called a piezoelectric material. Piezoelectric materials have the property that if you put a voltage through them they resonate, or they physically move. In addition, if you stimulate a piezoelectric material with a moving wave, it will create a voltage. Voltages get transmitted into movements. In this transducer the movement gets transmitted into sound wave–is what produces the sound waves that get transmitted into your skin and through your body. Because these piezoelectric materials can both form sound when they’re stimulated and they can detect sound and convert it into electricity when they’re stimulated by sound, then the transducer is both sending out sound waves and receiving sound waves back.

These work basically by the same principle that an echo works. If I shout in the right kind of a room where there’s nothing to absorb the sound between me and the back wall, the sound will hit the back wall and it will be reflected back to me. I will hear that sound some time interval later. You’ve all had the experience of hearing an echo. The same thing happens here, you transmit sound into the skin and it moves forward until it hits an interface. Sound doesn’t move so well across interfaces, so it moves through your skin and it goes down and hits the bone. There’s an interface between materials here that have two different properties: skin, muscle, bone. At each one of those interfaces some of the sound bounces back.

Since the detector is both sending sound and receiving sound, it sends out a sound wave and then it gets the sound back. It can determine how long it took for the sound to come back. If I know the speed of sound and I know how long it took for an echo to return, I can calculate how far away the object was that created the echo or the interference. Ultrasound works by sending out sound waves that bounce back, are received, and the machine calculates how long it took for this echo to go out and come back. Then, it knows there must have been some kind of an object at that distance away. Does that make sense? Ultrasound creates echo time maps and calculates depths from that.

Here’s an ultrasound image of the heart and it’s the heart turned upside down. This vaguely familiar to you from a few weeks ago, but the atria are on the top and the–or the atria are on the bottom and the ventricles are on the top. That’s just to show you in alignment with this image here. The probe is placed on the chest, for example, and it’s moved from side to side at one location. So, what you see is an image of what the probe can see as it sort of sweeps out this cone where the sound is moving. What you see is that there are boundaries between light and dark regions here, and those correspond to boundaries in the tissue. You can see the right atrium, you can see the right ventricle over here. You can see the left atrium and the left ventricle because the white region is the muscular tissue of the heart, and the darker region is the blood that’s within the heart.

Now, you’ll notice that it’s kind of a–it’s not a sharp image like the images that I showed you with CT, or the images that I showed you with MR. It’s a noisier image and there are–there’s a lot of sort of white spots or dark spots throughout it. Those are things that are called speckles, it’s talked about in your book. There are random sources of interference with the ultrasound image. The reason why ultrasound is useful is because you can watch things with time, and so you can see motion. In static pictures it looks like a very noisy image, but if you were watching this in real time you would see the motion of the heart. The speckles wouldn’t be as obvious because you’d be noticing more how the walls of the ventricle move, for example, in time. That would be very clear from the image.

What would also be clear to you is the motion of the valves, and we talked about the very critical role that valves play in the function of your heart. If your valves aren’t working right you can’t make an efficient heartbeat, that is, a heartbeat that produces a cardiac output. Ultrasound imaging has been one of the most used tools for looking at valve disease, and that event is called echocardiography. Have you ever heard of that term echocardiography? Which is basically ultrasound of the heart and it’s used principally to look at the function of your valve, the mitral valve and the tricuspid valve, here. If this was a video image you would see the valves opening and closing in correct coordination hopefully with the contraction of the heart. Ultrasound allows you to look at motion, and so to see things that are moving that would be difficult to do with other techniques.

You also know, and probably all of you in this room have–pictures were taken of you when you were in utero.Ultrasound imaging is a very common form of fetal monitoring now, where almost every woman who is pregnant has at least one ultrasound image taken at some course during the pregnancy just to make sure that the pregnancy is proceeding properly. This is an example of an ultrasound image, it looks the same way, an ultrasound image of an infant. This is the kind of ultrasound imaging machine that you might find in an obstetrics office.

You can see, in this particular case, that here’s the head of the fetus, here’s an arm, here’s the torso. Again, it’s not a very sharp image, but if you were watching this in real time as the technician moved the probe around on the pregnant woman’s abdomen, you would see the baby moving. You would be able to distinguish parts much more easily in that way because you’re moving both the probe and the baby’s moving, and you’re seeing things from different angles in real time as it’s happening. This is a very common technique. I wouldn’t be surprised if many of you, if you don’t have a picture of yourself in utero in your scrapbook, probably your mother has one somewhere, all infants of your age were ultrasound.

Ultrasound is also a good technique for looking at flow. When you look at flow you’re taking advantage of something called the Doppler effect. In physics you’ve probably heard about the Doppler effect. A simple way of thinking about it is if you’re standing on the street and there’s an ambulance coming towards you or a car that’s coming towards you and the horn is honking. As the car is approaching you, you hear a certain frequency of sound that changes as the car passes. The frequency of the sound that you hear depends both on the frequency of the sound that’s being emitted by the siren and the speed that the ambulance is moving relative to you. When the ambulance is moving towards you, you hear a frequency that’s offset from the real frequency of the siren. When it’s moving away from you its offset even more and you can hear that.

If I’m doing ultrasound imaging, imaging with sound waves, of an object that’s moving away from the probe, I can detect both where it is and how fast it’s moving by the frequency of the signal that’s returned to the probe. That allows you to image the rate of blood flow through vessels, and that’s shown in this picture here. You can measure the rate of blood flow through the carotid arteries, for example. That turns out to be a very useful technique for patients that have cerebral vascular disease. They’re getting arthrosclerosis or hardening of the arteries in the important vessels going up to their neck that can be measured–through their neck up to their brain that can be measured using ultrasound.

Those two methods–magnetic resonance ultrasound having the big advantage, that they don’t involve ionizing radiation. Magnetic resonance imaging in general takes a long time, requires very expensive equipment. Ultrasound imaging can be done in real time. You can take pictures, images of the inside rapidly. The equipment is not so expensive, so any doctor’s office can have an ultrasound machine. The image quality is not as high, but you can image things that are in motion. These imaging approaches are used for different applications because of the advantages that each one has.

Chapter 5. Nuclear Medicine [00:44:22]

I want to talk briefly about nuclear medicine. I’m going to have to go fast here. This does use a form of ionizing radiation, in particular, gamma rays. Gamma rays are produced by nuclear events, events inside the nucleus; in particular, they happen when radioactive isotopes decay. When radioactive isotopes like Zenon-133, Technetium-99, Iodine-123, these are unstable isotopes of these molecules. So, with a certain frequency, they will decay back to their more stable form. When they decay, they emit a form of radiation called gamma radiation, many of these. Gamma rays–remember on the electromagnetic spectrum, they were up there with X-rays, high frequency, short wavelength radiation, penetrates easily through tissue but is also an example of ionizing radiation.

Now, the difference between nuclear medicine and–what’s called nuclear medicine and conventional X-rays is in X-rays, the X-ray source was outside of you and you were being bombarded with X-rays. In nuclear medicine, the gamma ray source is injected inside of you. What you measure is the amount of radiation that comes out. Now, what’s the advantage of that? Well, the advantage is if I can find radioisotopes that concentrate in certain regions of your body and I inject those isotopes into you, and then measure where they are, I can measure the function of that particular region of your body.

The first imaging that was done was done in the thyroid and your thyroid has a very active mechanism for concentrating iodine. Because of that if I feed somebody radioactive iodine that iodine will accumulate in their thyroid gland which is in your neck. The rate at which it accumulates and the pattern at which it accumulates can indicate whether you have a healthy or a diseased thyroid. If I, then, take images of the thyroid after I’ve injected the radioactivity and I look to see if the radioactivity is there, and how fast it gets there, and how fast your body removes it, then I can learn something about how your thyroid is functioning because of its ability to concentrate iodine. That’s one example of it.

Imagine you have a chemical that accumulates in the brain and accumulates only in certain areas. For example, you have a chemical that’s related to the neurotransmitter dopamine and you give it to a patient that you suspect of having Parkinson’s Disease. Well, Parkinson’s Disease involves the brain neurons that process and use dopamine and so if this radio chemical goes up into the brain it’s going to interact with those cells that are involved in Parkinson’s Disease. By watching how this molecule moves around in the brain I can learn about how your brain is processing dopamine and if it’s responding in a normal sort of way. Does that make sense? The advantage of nuclear medicine is that you’re designing very specific kinds of radioactive molecules that you can put into the body. The molecules are designed to illuminate some kind of biological function, not structure. Then, I measure the time course of how those objects–how those radio labeled compounds move through your body.

There are several ways of measuring it. I’m just going to show you the simple one here; not simple one but a very powerful one called Positron Emission Tomography. Here the chemical that’s emitted is a special radio isotope that emits not gamma rays but another nuclear–another particle called a positron. When positrons are emitted, they will move through tissue until they hit an electron. Positrons don’t have to move very far, there’s lots of electrons around in tissues. When a positron hits an electron, they annihilate one another and they generate two gamma rays which move in opposite directions. If I have a positron emitting substance in the brain, it will emit gamma rays which can be detected. Because I’m detecting one here and one here, I know exactly where the source came from. I can trace it back along the lines where I detected the gamma rays and I can find out where the positron emitting element was. So, I can make very nice maps of the brain like these that show you where the positron emitting isotope accumulates in the brain. This is called PET imaging.

I’m going to skip over this one which tells you a little bit about the economics of these different modalities. Ultrasound, as I mentioned, was cheaper; CT costs more, MR in general cost more, PET imaging costs even more because you have to generate radio isotopes locally at the source too. In general you need a cyclotron or some kind of a machine to generate these radio isotopes as well. There are other things you have to think about if you’re thinking about installing these, is how much do they cost to operate and how heavily do technicians have to be involved in order to keep them working.

Chapter 6. Optical Imaging and Conclusion [00:49:56]

The last thing I want to talk about is optical imaging, and as I mentioned last time, I think that during your lifetime we’re going to see a lot of new approaches for using light to image inside the body. That’s a problem because light doesn’t penetrate through your body, it bounces off; most of it bounces off. That’s why we can see each other, because we’re seeing the reflected light off of different objects. You can use light to look at biological objects. You can look at them in great detail this way and that’s what microscopes do. They allow you to use light radiation in order to look at magnified images of biological objects. We’ve gotten very good at designing microscopes that allow us to look at, in very sophisticated ways, at biological objects on the stage of a microscope.

This just shows you an image, it’s actually very similar to the CT scans or MR scans I showed you before, in that these are different optical sections taken from a pollen grain. A pollen grain is very small. Here’s an image from the bottom moving up, moving up, moving up–this shows you all the three dimensional detail of this particular pollen grain. You can reconstruct in three dimensions and see what it looks on the outside, or you could look and see what it’s like at any point in its interior structure. We’re very sophisticated at using light to make images like this now on microscope stages. One could take very beautiful pictures of biological objects like cells with different kinds of optical techniques.

Here’s–this is familiar to you, this is a glomerulus. I told you what a glomerulus was last week, but this shows sort of the tuft of capillaries inside a glomerulus imaged by light microscopy. Well, how do I take advantage of this kind of microscopy but look at these kinds of images inside people? We don’t how to do that yet, but we do have some technologies for looking at–using light to look inside and the main one is called endoscopy. Endoscopy involves objects called fiber optics, and fiber optics allow you to not only focus light through a lens but to take that light and bounce it down an optical shaft. I could take a light beam and shine it here into a fiber. That fiber has a special coating on which then allows the light to bounce all the way down the fiber. I can bend the fiber, and because the bouncing depends on the coating and not the shape of the fiber, the light will turn with the fiber. This is how fiber optics works; it’s described a little bit more in detail in your book.

One can design devices like this endoscope. This endoscope you can look through this end here, it has a light source. That light source shines through fiber optics that you can bend around, and that light comes out the outside. If the light comes out the outside it hits some biological object and then bounces back light, reflects light and you can see it. You can look inside objects where you can put this endoscope. This endoscope is designed to go–a patient will swallow it. This end will go down in their mouth, past their vocal chords, through their esophagus, into the stomach, and then out of the stomach into the duodenum or the first part of the small intestine. That’s what’s shown here.

This is the valve that’s leading from stomach into the duodenum or the first part of the small intestine. You can see what the lining of the small intestine and the stomach looks like. This has been a very important diagnostic approach for using light to image the lining of the stomach. What would you be looking for? Things like ulcers, things like cancers, any kind of disturbance in the normal anatomy of the lining of the gut. I think you’re going to see a lot of new methods beyond this for using light to look inside people as well. I’ll stop there. Thanks.

[end of transcript]

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