BrainLane.net productions presents –



Brain Imaging
With
Dr. Paul Thompson, Ph.D.

Assistant Professor of Neurology
UCLA School of Medicine

By,
Paul D. Costa

In April of 2003, I interviewed Dr. Paul Thompson; at the UCLA Laboratory of Neuro Imaging.  I was first told of Dr. Thompson’s work by Dr. Wes Ashford, the lead M.D., Ph.D. for the End Alzheimer’s 2012 Task Force and was anxious to see first hand the advances Dr. Thompson was making in computer graphic assisted brain scan and data extrapolated imaging.

  Years ago, I had the good fortune of working with Silicon Graphics in the motion picture and virtual reality industries and I was aware of their scientific division's work in medical imaging – but I wasn’t expecting the powerful imaging production that I saw. The entire interview will be available in video CD soon and here most of the interview is presented without editing.

  PDC:   Dr. Thompson, could you give me a brief overview of where brain imaging is today?

  PT:  There are really a couple of different ways of scanning the human brain. One of them is called PET scanning and that gives you a picture of the amount of energy the human brain is using. One of the reasons you might want to know this is in neurological disorders or diseases like Alzheimer’s, or multiple sclerosis – you want to know if the brain is physically functioning in the way you expect it to.  And even if the amount of energy that the brain is using is about right – just like with any other organ of the body – a PET scan tells you how you are really using energy in various parts of the brain.

 

And it will tell you if your memory systems or your language systems – all of these different areas of the brain – are active as they should be. These are typically shown as color images, and these are ones where you might see a red area where the brain is very active and a blue area where it is not as active as you would expect it to be. That’s one type of scanning called PET scanning.

  A little more recently  (PET scanning is maybe 20 years old), MRI or magnetic resonance imaging was developed. This has been around about ten years or so. This images the structure of the brain – I told you about PET scanning, where that is a map of the activity or energy levels of the brain - often what you want to know is about the anatomy of the brain – is it intact? Think of it like an X-ray. If you could get a very very detailed X-ray – an MRI really looks at the anatomy of the brain and sees how it looks structurally.

  PDC: What is the driving motive here in the UCLA imaging labs?

  PT: One of the things we are interested in doing in this laboratory is to understand what parts of the brain do specific things. Now there is a road map to the brain and let me give you a little bit of an introduction to that. So, essentially the brain is organized a little bit like a jigsaw. Each of these different areas does different things. This area is called the temporal lobe, just below the ears – that is involved in learning and memory. If you try to remember a telephone number or someone’s face -  there is actually activity going on there. If this area damaged, you might have difficulty remembering those particular events.

  This area here – this tiny territory there is actually involved in understanding language. If you are listening to someone speaking, or watching television, and understanding the words you are hearing, this area is processing the words and all the information you are hearing.

  This area of the brain is the frontal lobe – the CEO or executive of the brain. This area is involved in behavioral planning – the cells here define what you are going to do in the future. They are also involved in inhibition and self-control. If cells here are declining, you often see inabilities to control behavior or inhibitions as well.

  The last area is the central gyrus, also called the primary sensorimotor area of the brain – this is involved in sensation. There is actually a physical map where you can feel sensations from your feet or your face and other parts of the body. There is actually activity that goes on in each of these particular regions.  Almost, as we have said, there is a "mosaic" of different areas, and each of these different modules does a separate thing.

  PDC: How do patients and doctors use these imaging technologies and has it made that significant of a difference?

  PT: In other conditions such as stroke, you’ll see little areas of the tissue that have been affected. Maybe a blood vessel has changed, or maybe in the case of a brain tumor you’ll want to see where that is, or rule out other causes of disease. In all these cases you’d use an MRI scan, essentially it is the same principle - a patient sits in an MRI scanner – and you get a very detailed 3-D image of the brain. A radiologist or doctor will look at that  and they will try to say which part of the brain is effected. And that might be used to explain some of the symptoms a patient has – if they are losing their memory they will look in the areas of the brain that control memory, if they are having problems with language, they will look in those areas of the brain. Really to see if there is a physical sign of disease or, with the PET scan, to see if there is a little less activity in those areas of the brain.

  PDC: Has this close-up “snapshot” point of view changed our concepts about the brain? And has it changed our understanding of how the brain functions?

  PT: Yes, essentially the brain is made up of millions of millions of cells – just like any other organ of the body. What’s different about these cells is they actually talk to each other. You can think of it a little bit like the Internet, where you have the computers on the Internet and the wires between them.  So all these brain cells make up brain tissue but they have wires or connections that allow the brain cells to communicate. Now the way the brain cells communicate is through chemical messages and electrical messages. So just as though you might be on a computer on the Internet you’d send a message from your computer to other computers – your brain sends electrical impulses from one cell to another. Now when the brain is healthy all of these electrical messages are being transmitted in the correct way – so all the cells are organized correctly and they are shuttling messages from one cell to the other. When the cells begin to break down though – this might happen in aging or it might happen in a brain disease – you’ll begin to see signs that all the information may not be getting to the right place. And examples might be in Alzheimer’s - memory fails because of a breakdown in memory cells, in other brain diseases perhaps another particular brain function is affected.

  If someone has a stroke in a language area of the brain their speech may be affected – but other areas such as vision and hearing will be fine for them. So one of the ways we are beginning to understand how the brain works is to make physical maps and images of what different parts of the brain do. We know that the cells are sitting in different "islands" – some controlling vision, some hearing, some memory. We're beginning to get a more detailed picture of how the cells talk to each other in a healthy brain, and how they break down in disease.

  There is a very special portion of the brain called the hippocampus – this is where short term memories are processed – maybe if you are thinking of remembering a phone number so you can call someone. That actual memory is laid down in the brain in a small structure called the hippocampus. It is shaped a little bit like a teaspoon – a tiny structure in the shape of a cigar – and it is just inside the brain, beside the ears, on the inside surface of the brain. Now this is how this memory takes place. The things you want to remember usually come in as audio or visual stimuli - things you might see or hear. That information is trafficked – using the brain cells, to this very special memory area of the brain. And there are actual physical changes in the composition of that memory area. Now this may seem very strange, but a lot of the cells are changing. As you listen to this for example, your brain cells are responding and understanding the things being said. They actually are physically reorganizing the structure of the brain, at the level of the brain cells.

  So what I mean by that is the little connections that connect one brain cell to another – there are actually physical changes that go on in them. And that is actually storing information. If you want to recall a telephone number or remember a face- you see someone and want to recall their name or who that is - you are actually calling up a whole resource of memories. These memories are partially stored in the particular location of the brain called the hippocampus.

In diseases such as Alzheimer’s, we know that the physical degeneration of the brain makes it difficult to recall things, like short-term memories. And so a patient might have trouble recalling a phone number or remembering what they did that day – or remembering someone’s name if they see them.   That’s actually because the brain cells used in forming those memories and retrieving them are undergoing changes that are part of the disease. So as well as healthy changes that are part of learning, there are also changes that happen because of the diseases – there is an interplay between positive changes that are necessary throughout life – and also negative effects that make it more difficult to learn.

  PDC: It seems the process of learning is a complex chemical, electrical and physiological transaction – do we really understand what is going on and how can imaging help us in disease conditions?

  PT:  It is complex. When someone actually learns something – let’s say memorizing some information – there actually are a whole set of proteins and chemicals inside your brain cells that undergo change. Now this doesn’t only happen with one round of learning – it can continue as you practice something. Very often, with practiced behavior – something like learning how to ride a bicycle or practicing the piano – there are progressive physical changes inside a brain cell.

  Now let me tell you a little bit about what those are. When a brain cell is active – it is actually sending electrical impulses to other cells. So when you are thinking of a particular thing – the brain cells are firing impulses to a particular set of brain cells that involve that specific thing. So as they fire more and more – different proteins build up in those cells and there are physical changes in the chemistry of membranes of the brain cells – and what that means is it affects the ability of these cells to fire in the future.

So if you had a computer you were changing the composition of – making changes in the way it is wired – it would affect the ability of the computer to do different operations. What you see as you practice a behavior is actually your brain cells are firing – using electrical messages to talk to each other  – and then a second step involved in learning – is these actual building blocks of cells – the proteins or sugars or other elements of any part of the body are being made or restructured so the actual physical membranes of the cells are changing composition. And this translates into differences of how these brain cells fire. So, if a particular brain circuit is useful and helps you remember something – the actual physical structure will change in a way to make it easier for that set of cells to fire. And conversely, if you don’t use brain cells – and you are not learning something there is a degeneration or reduction in the amounts of these particular proteins. Now this is just being understood, and we now know a lot about the physiology of learning – how the brain cells talk to each other when someone learns a particular behavior – but we are only just beginning to understand what the actual proteins are, that are involved. The physical and chemical substrates of learning are really only beginning to be deciphered. There is this sort of progressive knowledge that when you learn something it isn’t just "in your mind". There is also a physical component to this as well.

One of the most exciting things about learning and memory and understanding how these things change as you age – is really seeing this in living patients. If you can understand the changes that occur in a patient as they begin to lose their memory or maybe help to save those memory processes – one way you can look at this is brain imaging.  Brain imaging is something people are familiar with – you go to a hospital and get a brain scan. It can actually give you a physical picture of how the brain is doing. Now a brain image doesn’t show you individual cells – but it shows you aggregate of millions of millions of cells – you’ll see what is known as gray matter – the "thinking part" of the brain. Even though it consists of millions of brain cells – looking at that brain scan can give you a lot of information about what those brain cells are doing. So if someone is learning, one theory is that we see the physical changes in the structure of the brain. One thing that is very easy to see on a brain scan if there are signs of early degeneration of memory areas. For example if a patient is having early memory problems – one of the things we see in their brain scan is the memory areas will actually shrink. There will be volume changes and these are visible at a global level. You could look at your own brain scan and say: “I think – compared to a couple of years ago – these memory areas are shrinking in size”.  What that means in terms of the cells is they are actually beginning to die off or changing in size and number – perhaps by atrophy or from a disease process.

The brain scan is telling you on the whole is there is evidence that cellular changes taking place.  It is a very exciting technology to monitor for early detection of a disease and really understand if the drugs are affecting either our memory or other brain diseases that might be taking place. You can think of brain scanning as a way of getting into the brain – similar to a digital photograph, but really assessing the integrity of the cells rather than the exterior of the body.

  PDC: What drew you to the study of the Alzheimer’s disease process?

  PT: One of my personal interests for many years is to try and understand human diseases. One of the diseases that really has a chance to be solved or cured is Alzheimer’s. Imaging offers the opportunity to capture a detailed picture of Alzheimer’s – catches it "red handed". It’s really a technology that allows you to say – “Are there signs of dementia that can put a patient’s memory at risk later?” Are there ways we can use imaging to help determine a patient’s therapy sooner? I personally have been excited about the promise that imaging has – it doesn’t in itself offer a cure for Alzheimer’s, but it gives you a detailed record of what is going on the brain. This can be used in drug assessment, it can be used to actually be used on a positive side to see if a brain is doing OK. It can be used on a research level to see what happens when a disease hits. We think we know what happens in Alzheimer’s – but that actual sequence of events is a bit of a mystery. One of the things I am trying to do is to reconstruct the physical changes that develop within a patient as they develop a disease, This might be Alzheimer’s, or one of numerous other neurological disorders, such as multiple sclerosis. In a sense the technology is the same, but it helps you see how these diseases unfold over time really with a goal to see what the changes are, and if they can be decelerated.

PDC: Tell me about the animation of the Alzheimer’s disease process.

   

PT: These are MRIs of a patient involved in an Alzheimer study -  one of the things you can do with MRI is section the brain and have a look at it from different angles. This is a three dimensional MRI scan – it takes about 8 minutes to perform. One of the things we are looking for in these images are there any early signs of Alzheimer’s. I’ll tell you some of the areas that are important – these are fluid filled areas here – they almost act like hydraulics and actually cause a sort of buffering to any mechanical sort of impact that happens. One of the things you see as you age is that these fluid filled spaces enlarge. Often one of the first signs of dementia is if these fluid filled spaces are a little bit bigger than they should be. One of the reasons this happens is as the brain cells degenerate – you actually get an increase in the size of these fluid filled spaces. They are pretty complex in geometry – it is like a labyrinthine complex system that threads through the brain. One of the things you are looking for is a sign that this is abnormally enlarged. Another area I’ll show you is the memory system. Here is the hippocampus –All the memories of what you are thinking of doing today – or what your plans are or maybe your remembering your schedule for later today – all these are being processed in this tiny area there called the hippocampus. This is another area you would look at, in these images, to see if there are any signs of change. Now the hippocampus is really the size of a teaspoon. It has a little "handle" and then there is a little piece at the end here – that brain tissue changes very drastically in aging and also in Alzheimer's Disease. One of the things you see is shrinkage – this patient actually looks like they are doing pretty well. Their hippocampus is a good size. The fluid that surrounds the hippocampus – it doesn’t look like there is a lot of it. This actually looks like a healthy brain. No signs of serious deterioration. One of the things you’d begin to see is these areas here – a little tract of tissue called the hippocampus and all the memory areas that begin to decline in AD and Aging – these are accompanied by a reduction in volume of the structure. This structure is called the hippocampus and again we begin to see a paring down of tissue structure here – a little bit like the cells were dying and at the same time you’d see an increase or enlargement of the fluid that surrounds the hippocampus as well. So this is really a target for Alzheimer’s therapy - you are looking at the structure and trying to save the cells in it. With a drug, you are trying to make sure the rate of loss of these cells is either stabilized or prevented by the use of therapy.

 

This is a horizontal section through the brain that has been taken with MRI scanning – you can see the patient’s eyes here and the nose. One of the areas of AD research that we are really interested in is the hippocampus – the reason for that is it is the structure that controls and lays down memories – things that you learn – the brain tissue is active in this little area of the brain.   What this scanner is doing is actually accessing the physical intactness of that tissue. So even though it is very tiny – you can tell this looks like a healthy subject – there is a lot of tissue in the area and that means the memory function is largely intact. This little fluid filled space here – that would be drastically increased in an Alzheimer’s patient – one of the reasons that happens is that the brain tissue surrounding the hippocampus begins to die off and as these cells die off you can see a corresponding enlargement of the fluid filled spaces. So this is really the target for Alzheimer’s drug therapy. Some of the drugs used can really save the cells here and you can use images like this to see if the drugs are slowing down rates of cell loss. Also to see if a patient is doing well – if you were to look at this area over a period of time you could see if the brain deterioration which usually takes place  is happening, at what rate it is happening, and where in the brain is the tissue being lost.

This animation shows these changes, and what happens as a patient develops AD over a year and a half. The red areas that you see here are areas where cells are actually being lost. As AD hits the brain there is this progressive "lava flow", which is sort of eating into the brain cells and eliminating them and resulting in the memory decline that you see. One of the earliest areas to be affected in AD is the memory system. One of the things you see is that the red areas – the areas that go into deficit – they are initially only in memory areas.  So this makes sense – a patient will have a deficit in memory and learning but not in vision or hearing. As this disease progresses you see this sort of wildfire of tissue loss that spreads across the brain. What this means is that over a year or two year period there is actually a progressive spread of the disease – the brain cells are being lost – not in the whole brain itself but in a sort of slowly spreading sequence. There is some logic as to how this happens – the memory systems are affected first – then the more "emotional" areas of the brain are affected and ultimately the areas of self-control are being eroded away. One of the things that the brain scan tells us is there is a physical basis for these changes the patient has. If we can use these scans as a record of what is happening in the brain. You can actually see if the physical spread of the disease is being halted or where a drug is slowing it down. So really this animation shows you two things – One is that AD is very selective, and, second, that there is a sequence of how brain tissue is affected.

PDC: That would be valuable information in therapy, are we at a point where the technology is being utilized?

PT: Almost, memory areas are affected, emotional areas are affected and then areas of self-control are affected. The second thing these animations show that is much more positive – is really they are telling you if in a particular patient the disease is being slowed down by a particular drug – whether things they are doing are warding off the rate of changes happening here. Even though this looks like depressing image – we are thinking in the near future these changes could be decelerated; these scans will give you a physical record of how well the patient is doing.

What happens when a patient gets Alzheimer’s disease – there are particular changes in their brain we are learning about. One of them is this molecular compound – beta-amyloid – a starchy substance that builds up in the brain – now amyloid is not always toxic by itself – but as it builds up in the brain more and more – a lot of properties of the brain cells that allow them to function normally – begin to be impaired. The first is the brain cell starts to be inflamed – the reason we know that is anti-inflammatory drugs – things like Celebrex or things like Aspirin – actually can give a lot of benefits in the early stage of Alzheimer’s.

The reason they are helping is the inflammation that is happening to those brain cells is actually being calmed a little bit. Now on the other hand the later stages of AD when the amyloid has built up quite a lot – it’s actually impairing the cells to a degree so they can’t function at all. So you begin to see brain cells dying – the amyloid starts killing off the brain cells at a tremendous rate and what you might see is as much as 5% of the brain cells a year- being killed in the brain of an Alzheimer’s patient. We know that that process is quite selective where amyloid - the molecule that is building up in Alzheimer’s – where that molecule is building up more brain cells there are cells being killed. It is almost like a two stage process- if you can keep some of those brain cells healthy in the brain – some of the degenerative effects that you see as brain cells die – might be warded off. 

PDC: Isn’t that the hope of pharmaceuticals and inoculation treatment approach – to alter the chemistry of the disease process and spoil it?

PT: Yes, and imaging has shown without a doubt there are a couple of different ways of warding this off. One of the ways is drug treatment and obviously drug companies are trying hard to keep the brain functions as intact as possible.   Really by beefing up the ability of brain cells to talk to each other.    So one of the drug treatments used in Alzheimer’s is called a cholinesterase inhibitor. And what that is actually doing is – you have depletion, as these brain cells die, of the chemicals that allow these brain cells to talk to each other. This drug treatment is affecting the way this compound is being depleted. You actually have "vacuums" in your brain that clear the chemicals that let the brain cells speak with each other. One of the drugs blocks these vacuums – it is an interesting mechanism – when you take these drugs you're actually inhibiting the clearance of the brain chemicals and this class of drugs really beefs up the brain cells speaking to each other. 

A second way that you can balance brain function that is not through drug treatments -  is really just common sense. So anything you can do to stay healthy things like nutrition or exercise – these are going to contribute to the physical health of the brain.   Now it is certainly known that your blood vessels and cardiovascular health is greatly improved with exercise.  This is identical with the brain – the more people exercise the more the gray matter of their brain is kept intact. This is the same tissue that is at risk in things like AD – and so even though exercise doesn’t directly prevent Alzheimer’s we know that anything you can do to keep you brain tissue healthy and intact – makes it more robust it makes it less easy for diseases like AD, or many others, to really take effect. So the things you see – is the many things we can do – things like good diet, exercising or really having a healthy lifestyle that isn’t damaging brain cells – all of these, like any other physical system, are helping to ward off the effects of ageing as well as the more pathological effects of Alzheimer’s as they build up. 

PDC You are talking here about the lifestyle and simple over the counter treatments that people can self-administer to himself or herself right? 

PT: Yes, and I think we are at a threshold point in imaging where a lot of things are possible for evaluating their effectiveness. One of the reasons I say this is the imaging technology has undergone a revolution in the last few years. We are now actually able to physically image the things that cause Alzheimer’s. Let me give you an example. The amyloid protein that builds up in the brain has never really been seen before – except at autopsy. Now that is interesting in terms of understanding the disease – but it doesn’t help living patients. 

There’s really been a revolution in imaging though that allows you to see where AD is spreading in the living brain. And it's not only these approaches that I’ve talked about with MRI – that are looking at the intactness of cells – but really a new window is created on the disease – partly because you can now also see these "rogue chemicals" that are building up on the brain. Now why would we want to do that? Well one of the ways that we can know if a drug or lifestyle is effective is looking for a physical marker for the disease. Now with scanning and imaging if someone has a tumor or a broken blood vessel - it is very easy use scanning to detect that and see how that patient is doing.

With Alzheimer’s disease until recently – it hasn’t been so easy. Alzheimer’s disease eliminates a small fraction of your brain cells per year – but it is actually moderately difficult to see in a brain scan if someone has Alzheimer’s or not. One of the revolutions in brain imaging is we now have scanning in exquisite detail – we can see changes in the order of 1% or half of a percent in the number of brain cells per year – this lets you see the physical process of aging in unprecedented detail. There are also newer imaging technologies as well – one new form is called amyloid imaging – this is relatively new its been developed over the past few years – and you can actually see the physical spread of the molecule causing Alzheimer’s - amyloid. And there is a lot of exciting ways this technology can be used in the future.  

PDC: Could the imaging technology be useful in verifying the effectiveness of immunotherapy – or the vaccine approach?

PT: In my opinion, yes. In trials that are using vaccines, the target of those trials is to eat up the amyloid that is building up in the brain. Now there is no better way than imaging to see if a patient’s amyloid is being cleared. Now clearly the "acid test" is at autopsy, to see if the plaques are still present. But certainly for a patient that is alive who wants to know if the brain function or the pathology is being arrested or opposed – you’d want to use the best of imaging you have available – really to see if the hallmarks of the disease – the physical signs of the disease – rather they have been cleared or they are progressing as the disease evolves.

Imaging is at a threshold where we can see some of the hallmarks of the disease for the first time. Some of the molecules we know that are implicated – we have only previously seen at autopsy. Now you can use imaging to see these molecules in living patients. Why that is useful is you really want a physical marker of the disease as patient is taking drugs or really as people are doing things to slow down the onset of the disease. These images give you a physical – quantitative measure of how well someone is doing – have they averted the disease by doing particular things or in the case of a patient has a drug treatment they have been having slowed down the disease or not.

PDC: Do you see the end of Alzheimer’s disease and the role imaging will play in that end?

PT: Well, there’s a lot of ways that I think will begin to bring about the end of Alzheimer’s disease – some of them are measures that anyone can take that delay the onset of AD – this "buys time". Some of the things we know are effective are exercise, cardiovascular fitness keeps the brain intact – and even healthy diet and nutrition are important to keep the brain healthy. A much more direct approach that I think will be revolutionary is the use of vaccines and other agents perhaps that we don’t know about yet – but based on vaccine technology that physically combat the causes of the disease.

As we said before, AD builds up in the brain - it doesn’t just hit you immediately. It plays out over a period of two to three years. Now even though this seems like bad news, it is actually a window of opportunity for drug treatments like vaccines or vaccines in concert with other drugs. Now in a sense AD is a paradoxical disease – there is a slow onset – it sort of sneaks up on people and then it doesn’t hit all at once.

There is a slow progression. One of the ways that the vaccine is promising is that they physically target the cause of the disease – so if we know these "rogue proteins" contribute to the memory decline and other symptoms the patient has – you can actually attack the protein. Some of the treatments that are experimental right now I think will be used in the future to clear the brain of the physical source of these symptoms. Now there are also other ways that lead to an onset of symptoms – even if we can’t clear the brain of the physical cause of the disease we can balance the function of brain cells – so there are major efforts at the drug companies worldwide essentially to help the brain’s chemicals communicate more effectively when the brain is under attack. Rather than combating the pathology itself it’s really sort of mustering the forces of the brain to keep the cognitive function, as it should be. Now since we know how brain cells talk to each other and the chemicals are very well known – it is comparatively more straightforward to try and affect these chemicals and beef up their functions. Let me give you an example – if someone has depression, we know that anti-depressants can be quite effective in eliminating or at least partially opposing depression. The reason that works is that often in depression the serotonins or the dopamine systems of the brain – these are different chemical messengers  - are altered. And so the drugs work by restoring the imbalance of those chemicals in the brain. Now in AD the situation is no different - the brain cells are degenerating in the brain – causing a chemical imbalance in the brain - and the way the brain cells communicate with each other – it isn’t just that they are dying – but the existing cells are having difficulty communicating with each other with these chemicals.

There are certain molecules – the neurotransmitter pathways where there is a lot of research going on. These chemicals are depleted in early Alzheimer’s – so one of the ways forward in drug therapy in Alzheimer’s is to see if there are ways to keep these chemicals around longer in the brain – so not just people who are worried about Alzheimer’s disease but also those who have it can keep their brain balanced for as long as possible.

One of the things we are interested in is to understand which parts of the brain are affected in brain disease. So let me give you a road map of the brain and those areas affected by diseases. One of the things you see here is the overall structure of the brain – it is actually separated into regions. Through a lot of research from many laboratories worldwide – we are now beginning to understand what these different parts do. This is an area just below the ears – it’s just on the exterior surface – this area is involved in memory  - a lot of the thoughts you are having when you try to recall a name or a telephone number or your interesting in what happened to you many years ago – there is a processing going on here – it’s called the temporal lobe. This is actually a very discrete area of tissue and if anything happens to the brain in this tissue area – it can actually impair memory function. So this is the first area to degenerate in the case of Alzheimer’s.

PDC: How do you see the pharmaceutical industry and the imaging communities working together?

PT:  I think the next few years will see a revolution in our ability to see understand how drugs are working to get rid of Alzheimer’s – and really to try and get new drugs on the market as fast as possible. One way that imaging can help is that there are certain areas of the brain – this is the memory area of the brain – where very very subtle changes take place early in Alzheimer’s. With imaging you can access the intactness of this – you can also look at Amyloid, one of molecules involved in Alzheimer’s that’s building up here. I think that a second revolution in our understanding of Alzheimer’s will take place if we can see the earliest possible signs of AD and deliver drugs to the patient as soon as possible so this brain tissue stays intact. We will see that drug development and imaging will work hand in hand, the drugs will actually combat the disease and the imaging will give you the best possible index of which drug is working – whether one drug is better than another – and if the physical spread of the disease is actually halted in concert with the symptoms.

PDC: What does this beanbag graphic brain image signify?

PT: This sort of "M&M" graphic of the brain is actually a map of how variable the structure of the brain is in a population of people. Just as there isn’t any one road map of a city, everyone’s brain is a little different. In early days, surgeons would plan surgeries using an individual brain. This image is actually a composite of many many brains – and what the different areas of color are telling you are – the pink areas are areas where your brain and my brain might be quite different – really the structures might be enormously different in those areas.  The blue areas are brain regions that are very consistent in anatomy between subject to subject. Now one of the points of having this is you would like a measure of variance of brain structure in a population. If you have a measure of that, you can tell if a brain is abnormal. Part of why it’s hard to tell if a brain is abnormal is that there is so much that’s different between normal healthy subjects. It is similar to faces – each face is different from any others – it is difficult to tell if a nose if out of place or something like that – because we don’t have a statistical record of what those features should be. But just looking at this again – the little beans describe regions of space where 95% of the normal population would have their anatomy. And so the "bigger beans" are areas that are very variable – the pink areas that you see there with the elongated beans - there is a lot of difference in where people’s brain function is located in those particular areas. But the areas that you see in blue everyone is kind of the same. A surgeon needs this for understanding what the variability is for planning a surgery – and also more practically for more accessing brain abnormalities. If someone’s fissures or grooves on the brain surface look abnormal – this provides you with a quantitative way of measuring if that brain is out of whack at that particular area: Is it different than the population? So what you can use this for is to give you a map of the abnormality of each brain region by consulting a database of population data.