Why are functional mris useful to doctors?

MRI Scans

  • Cardiac MRI (National Heart, Lung, and Blood Institute)
  • Chest MRI (National Heart, Lung, and Blood Institute)
  • Knee MRI (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance (MR) Defecography (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance Cholangiopancreatography (MRCP) (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance Imaging (MRI) – Spine (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance Imaging (MRI) — Head (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance Imaging (MRI): Dynamic Pelvic Floor (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Magnetic Resonance, Functional (fMRI) — Brain (American College of Radiology, Radiological Society of North America) – PDF Also in Spanish
  • MR Angiography (MRA) (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MR Enterography (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MRI of the Body (Chest, Abdomen, Pelvis) (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MRI of the Breast (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MRI of the Chest (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MRI of the Musculoskeletal System (American College of Radiology, Radiological Society of North America) Also in Spanish
  • MRI of the Prostate (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Shoulder MRI (American College of Radiology, Radiological Society of North America) Also in Spanish
  • Urography (American College of Radiology, Radiological Society of North America) Also in Spanish

What is Functional Magnetic Resonance Imaging (fMRI)?

Functional magnetic resonance imaging, or fMRI, is a technique for measuring brain activity. It works by detecting the changes in blood oxygenation and flow that occur in response to neural activity – when a brain area is more active it consumes more oxygen and to meet this increased demand blood flow increases to the active area. fMRI can be used to produce activation maps showing which parts of the brain are involved in a particular mental process.

The development of FMRI in the 1990s, generally credited to Seiji Ogawa and Ken Kwong, is the latest in long line of innovations, including positron emission tomography (PET) and near infrared spectroscopy (NIRS), which use blood flow and oxygen metabolism to infer brain activity. As a brain imaging technique FMRI has several significant advantages:

1. It is non-invasive and doesn’t involve radiation, making it safe for the subject.
2. It has excellent spatial and good temporal resolution.
3. It is easy for the experimenter to use.

The attractions of FMRI have made it a popular tool for imaging normal brain function – especially for psychologists. Over the last decade it has provided new insight to the investigation of how memories are formed, language, pain, learning and emotion to name but a few areas of research. FMRI is also being applied in clinical and commercial settings.

How Does an fMRI Work?

The cylindrical tube of an MRI scanner houses a very powerful electro-magnet. A typical research scanner has a field strength of 3 teslas (T), about 50,000 times greater than the Earth’s field. The magnetic field inside the scanner affects the magnetic nuclei of atoms. Normally atomic nuclei are randomly oriented but under the influence of a magnetic field the nuclei become aligned with the direction of the field. The stronger the field the greater the degree of alignment. When pointing in the same direction, the tiny magnetic signals from individual nuclei add up coherently resulting in a signal that is large enough to measure. In fMRI it is the magnetic signal from hydrogen nuclei in water (H2O) that is detected.

The key to MRI is that the signal from hydrogen nuclei varies in strength depending on the surroundings. This provides a means of discriminating between gray matter, white matter and cerebral spinal fluid in structural images of the brain.

Oxygen is delivered to neurons by hemoglobin in capillary red blood cells. When neuronal activity increases there is an increased demand for oxygen and the local response is an increase in blood flow to regions of increased neural activity.

Hemoglobin is diamagnetic when oxygenated but paramagnetic when deoxygenated. This difference in magnetic properties leads to small differences in the MR signal of blood depending on the degree of oxygenation. Since blood oxygenation varies according to the levels of neural activity these differences can be used to detect brain activity. This form of MRI is known as blood oxygenation level dependent (BOLD) imaging.

One point to note is the direction of oxygenation change with increased activity. You might expect blood oxygenation to decrease with activation, but the reality is a little more complex. There is a momentary decrease in blood oxygenation immediately after neural activity increases, known as the “initial dip” in the hemodynamic response. This is followed by a period where the blood flow increases, not just to a level where oxygen demand is met, but overcompensating for the increased demand. This means the blood oxygenation actually increases following neural activation. The blood flow peaks after around 6 seconds and then falls back to baseline, often accompanied by a “post-stimulus undershoot”.

What Does an fMRI Scan Look Like?


The image shown is the result of the simplest kind of fMRI experiment. While lying in the MRI scanner the subject watched a screen which alternated between showing a visual stimulus and being dark every 30 second. Meanwhile the MRI scanner tracked the signal throughout the brain. In brain areas responding to the visual stimulus you would expect the signal to go up and down as the stimulus is turned on and off, albeit blurred slightly by the delay in the blood flow response.

Researchers look at activity on a scan in voxels — or volume pixels, the smallest distinguishable box-shaped part of a three-dimensional image. The activity in a voxel is defined as how closely the time-course of the signal from that voxel matches the expected time-course. Voxels whose signal corresponds tightly are given a high activation score, voxels showing no correlation have a low score and voxels showing the opposite (deactivation) are given a negative score. These can then be translated into activation maps.

* * *

This article is courtesy of FMRIB Centre, Department of Clinical Neurology, University of Oxford. It was written by Hannah Devlin, with additional contributions by Irene Tracey, Heidi Johansen-Berg and Stuart Clare. Copyright © 2005-2008 FMRIB Centre.

What is Functional Magnetic Resonance Imaging (fMRI)?

What is an fMRI scan and how does it work?

By Megan Tung
An fMRI scan is a functional magnetic resonance imaging scan that measures and maps the brain’s activity. An fMRI scan uses the same technology as an MRI scan. An MRI is a noninvasive test that uses a strong magnetic field and radio waves to create an image of the brain. The image an MRI scan produces is just of organs/tissue, but an fMRI will produce an image showing the blood flow in the brain. By showing the blood flow it will display which parts of the brain are being stimulated.

MRI Machine (used for both MRI and fMRI scans)

History
In the 1930s Columbia University physicist, Isidor Isaac Rabi, discovered when a magnetic field combines with radio waves it causes the nucleus of an atom to “flip.” Most of the atoms in the human body are hydrogen atoms, which have a positively-charged proton within the nucleus. When the MRI machine emits a magnetic field the protons align with the magnetic field. Radio waves then pulse into the patient’s head, knocking the protons out of alignment. As the protons move back into their original position (called precession) they produce a radio signal back. The time and amount of re-alignment changes based on the thickness and hardness of the tissue. The radio waves emitted from the protons produce a clear image of the brain. In the 1900s, physicist Seiji Ogawa discovered oxygen-poor blood was affected by a magnetic field differently than oxygen-rich blood. The data showed oxygen-poor blood and oxygen-rich blood differed by 20%. The active parts of the brain contain more oxygen-rich blood, so this knowledge initiated research being done about fMRI scans.
Process the protons (in hydrogen atoms) go through during an MRI

How does an fMRI map the brain’s activity?
As I mentioned above, the fMRI looks at blood flow in the brain to detect areas of activity. Glucose is the brain’s primary source of energy, but glucose is not stored in the brain. So when parts of the brain need energy to perform an action, more blood flows in to transport glucose to the active areas, thus more oxygen-rich blood enters the area. For example, when you are speaking there is glucose and oxygen-rich blood flowing to the part of your brain designated to speaking.
During an fMRI scan the patient is asked to perform a specific task to increase oxygen-rich blood flow to a certain part of the brain. Such as tap their thumb against their fingers, look at pictures, answer questions on a screen, think about actions based off a picture (ex: they see a picture of a book and think about actions like read a book, write a book, buy a book), etc. For the tasks where the patient is asked a question, most of the time the patient is told to just think about the answer that way the speech part of the brain is not activated as well.
Process the protons (in hydrogen atoms) go through during an MRI

How does an fMRI help?
The primary reason for an fMRI scan is to help map a patient’s brain before they go into brain surgery. Creating this map will help doctors better understand the regions of the brain linked to critical functions such as speaking, walking, sensing, or planning. The brain activity is mapped in squares called voxels, which represent thousands of neurons. Color is then added to the image to create a map of the brain.
There are clinical studies that take multiple fMRI scans to research more about the scan and data it provides. Some believe with more research and development fMRI scans will eventually allow doctors to get a look at people’s mental processes (what they are thinking and feeling). If this is possible, fMRI scans could possibly be used to detect lies versus truths, which could act as more evidence in a court case. However, tons of further research needs to be done before this is actually possible.
Doctors have to be extremely cautious when operating on the brain, so an fMRI cannot be the only method to map the brain when any type of brain surgery is involved. Another method to map out the brain is called intraoperative brain mapping.** An fMRI scan is a great first step to ensuring the doctor has a deep understanding of their patient’s brain prior to surgery. Typically intraoperative brain mapping is used when a tumor/part of the brain needs to be cut out. The fMRI will create a general map of the brain, but the intraoperative brain mapping will allow the doctors to know exactly what parts of the brain are surrounding the part of the brain that needs to be operated on. This method happens during a brain operation by cutting the skull open and using a small electrical probe to stimulate the brain in different ways. The doctors will place the electrode on the brain stimulating in a variety of ways depending on the location. For example, the doctor could stimulate a part of the brain and the patient might think someone is touching their arm even if nobody is near their arm. Or a part of the brain could be stimulated causing the patient to have trouble talking meaning this part of the brain is responsible for speech. The actual electrode (or its pulses) will not hurt the patient, but the electrode might stimulate a part of the brain correlated to pain. The electrode can also stimulate seizures. However, the doctors can see the patient’s brainwaves, so if the doctor sees signs leading to a seizure, they will take a break from stimulating the brain. They can also give the patient anti-seizure medication. But if a seizure still does happen, cold water directly applied to the brain will almost immediately stop the seizure.

**There are various methods to map the brain, but I am just discussing one example of an invasive method and one example of a non-invasive method.
Pros
An fMRI scan is a non-invasive procedure that allows doctors to map out the brain before a surgery. This scan provides more information to the doctors about the makeup of an individual’s brain to prevent serious injuries or to determine if surgery is even a possibility. Another positive is the image produced by the fMRI scan is very high resolution.
Cons
Getting an fMRI scan is a very expensive procedure (most of the time*); however, it is worth the price if the scan could prevent someone from losing a necessary function. A minor negative is the machine can only capture a clear image if the person being scanned stays completely skill, but this can be solved with braces/harnesses to hold the patient in place. Finally, researchers do not fully understand every aspect of this process. In the scan they can only look at the blood flow, not at individual neuron’s activities (which is critical to mental function). When a certain area of the brain gets increased blood flow it can represent multiple different functions because it can be hard to isolate the brain performing only one specific action.
*There are clinical trials that will actually pay you money to allow them to scan your brain so they are able to gather more data.
You may also like reading:
Magnetic Fields, My Story as an MRI Tech Intern
The Powerful Magnets of an MRI Machine
Archive: How It Works Megan Tung is a summer intern at Jameco Electronics and a freshman at University of California, Santa Barbara (UCSB). Her interests include photography, music, business, and engineering.

What does fMRI measure?

Fig 1. From Kuo, Stokes, Murray & Nobre (2014)

When you say ‘brain activity’, many people first think of activity maps generated by functional magnetic resonance imaging (fMRI; see figure 1). As a non-invasive braining imaging method, fMRI has become the go-to workhorse of cognitive neuroscience. Since the first papers were published in the early 1990s, there has been an explosion of studies using this technique to study brain function, from basic perception to mind-reading for communicating with locked-inpatients or detecting lies in criminal investigations. At its best, fMRI provides unparalleled access to detailed patterns of activity in the healthy human brain; at its worst, fMRI could reduce to an expensive generator of 3-dimensional Rorschach images. To understand the relative strengths and weaknesses of fMRI, it is essential to understand exactly what fMRI measures. Without delving too deeply into the nitty-gritty (see below for further reading), we will cover the basics that are necessary for understanding the potential and limits of this ever popular and powerful tool.

“fMRI does not directly measure brain activity”

First and foremost, electricity is the language of the brain. At any moment, there are millions of tiny electrical impulses (action potentials) whizzing around your brain. At synaptic junctions, these impulses release specific chemicals (i.e., neurotransmitters), which in turn modulate the electrical activity in the next cell. This is the fundamental basis for neural communication. Somehow, these processes underpin every thought/feeling/action you have ever experienced. Our challenge is to understand how these electric events give rise to these phenomena of mind.

However, fMRI does not exactly measure electrical activity (compare EEG, MEG, intracranial neurophysiology); but rather it measures the indirect consequences of neural activity (the haemodynamic response). The pathway from neural activity to the fMRI activity map is schematised in figure 2 below:

Fig 2. From Arthurs & Boniface (2002)

Fig 3. From Oxford Sparks

To summarise, let’s consider three key principles: 1) neural activity is systematically associated with changes in the relative concentration of oxygen in local blood supply (figure 3); 2) oxygenated blood has different magnetic susceptibility relative to deoxygenated blood; 3) changes in the ratio of oxygenated/de-oxygenated blood (haemodynamicresponse function; figure 4) can be inferred with fMRI by measuring the blood-oxygen-leveldependent (BOLD) response.

Fig 4. Haemodynamic response function

So fMRI only provides an indirect measure of brain activity. This is not necessarily a bad thing. Your classic thermometer does not directly measure ‘temperature’, but rather the volume of mercury in a glass tube. Because these two parameters are tightly coupled, a well calibrated thermometer does a nice job of tracking temperature. The problem arises when the coupling is incomplete, noisy or just very complex. For example, the haemodynamic response is probably most tightly coupled to synaptic events rather than action potentials (see here). This means certain types of activity will be effectively invisible to fMRI, resulting in systematic biases (e.g., favouring input (and local processing) to output neural activity). The extent to which coupling depends on unknown (or unknowable) variability also limits the extent to which we can interpret the BOLD signal. Basic neurophysiological research is therefore absolutely essential for understanding exactly what we are measuring when we switch on the big scanner. See here for an authoritative review by Logothetis, a great pioneer in neural basis of fMRI.

“spatial resolution”

Just like your digital camera, a brain scan can be defined by units of spatial resolution. However, because the image is 3D, we call these volumetric pixels, or voxels for short. In a typical scan, each voxel might cover 3mm3 of tissue, a volume that would encompass ~ 630,000 neurons in cortex. However, the exact size of the voxel only defines the theoretically maximal resolution. In practice, the effective resolution in fMRI also depends on the spatial specificity of the hemodynamic response, as well as more practical considerations such as the degree of head movement during scanning. These additional factors can add substantial spatial distortion or blurring. Despite these limits, there are few methods with superior spatial resolution. Intracranial recordings can measure activity with excellent spatial precision (even isolating activity from single cells), but this invasive procedure is limited to animal models or very specific clinical conditions that require this level of precision for diagnostic purposes (see here). Moreover, microscopic resolution isn’t everything. If we focus in too closely without seeing the bigger picture, there is always the danger of not seeing the forest for all the trees. fMRI provides a good compromise between precision and coverage. Ultimately, we need to bridge different levels of analysis to capitalise on insights that can only be gained with microscopic precision and macroscopic measures that can track larger-scale network dynamics.

“snapshot is more like a long exposure photograph”

Fig 5. Wiki Commons

Every student in psychology or neuroscience should be able to tell you that fMRI has good spatial resolution (as above), but poor temporal resolution. This is because the haemodynamic response imposes a fundamental limit on the time-precision of the measurement. Firstly, the peak response is delayed by approximately 4-6 seconds. However, this doesn’t really matter for offline analysis, because we can simply adjust our recording to correct for this lag. The real problem is that the response is extended over time. Temporal smoothing makes it difficult to pinpoint the precise moment of activity. Therefore, the image actually reflects an average over many seconds. Think of this like a very long long-exposure photograph (see figure 5), rather than a snapshot of brain activity. This makes it very difficult to study highly dynamic mental processes – fast neural processes are simply blurred. Methods that measure electrical activity more directly have inherently higher temporal resolution (EEG, MEG, intracranial neurophysiology).

“too much data to make sense of”

A standard fMRI experiment generates many thousands of measures in one scan. This is a major advantage of fMRI (mass simultaneous recording), but raises a number of statistical challenges. Data mining can be extremely powerful, however the intrepid data explorer will inevitably encounter spurious effects, or false positives (entertain yourself with some fun false positives here).

This is more of an embarrassment of riches, rather than a limit. I don’t believe that you can ever have too much data, the important thing is to know how to interpret it properly (see here). Moreover, the same problem applies to other data-rich measures of brain activity. The solution is not to limit our recordings, but to improve our analysis approaches to the multivariate problem that is the brain (e.g., see here).

“too many free parameters”

There are many ways to analyse an fMRI dataset, so which do you choose? Especially when many of the available options make sense and can be easily justified, but different choices generate slightly different results. This dilemma will be familiar to anyone who has ever analysed fMRI. A recent paper identified 6,912 slightly different paths through the analysis pipeline, resulting in 34,560 different sets of results. By fully exploiting this wiggle room, it should be possible to generate almost any kind of result you would like (see here for further consideration). Although this flexibility is not strictly a limit in fMRI (and certainly not unique to fMRI), it is definitely something to keep in mind when interpreting what you read in the fMRI literature. It is important to define the analysis pipeline independently of your research question, rather than try them all and choose the one that gives you the ‘best’ result. Otherwise there is a danger that you will only see what you want to see (i.e., circular analysis).

“…correlation, not causation”

It is often pointed out the fMRI can only provide correlational evidence. The same can be said for any other measurement technique. Simply because a certain brain area lights up with a specific mental function, we cannot be sure that the observed activity actually caused the mental event (see here). Only an interference approach can provide such causal evidence. For example, if we ‘knock-out’ a specific area (e.g., natural occurring brain damage, TMS, tDCS, animal ablation studies, optogenetics), and observe a specific impairment in behaviour, then we can infer that the targeted area normally plays a causal role. Although this is strictly correct, this does not necessarily imply the causal methods are better. Neural recordings can provide enormously rich insights into how brain activity unfolds during normal behaviour. In contrast, causal methods allow you to test how the system behaves without a specific area. Because there is likely to be redundancy in the brain (multiple brain areas capable of performing the same function), interference approaches are susceptible to missing important contributions. Moreover, perturbing the neural system is likely to have knock-on effects that are difficult to control for, thereby complicating positive effects. These issues probably deserve a dedicated post in the future. But the point for now is simply to note that one approach is not obviously superior to the other. It depends on the nature of the question.

“…the spectre of reverse inference”

A final point worth raising is the spectre of reverse inference making. In an influential review paper, Russ Poldrak outlines the problem:

The usual kind of inference that is drawn from neuroimaging data is of the form ‘if cognitive process X is engaged, then brain area Z is active’. Perusal of the discussion sections of a few fMRI articles will quickly reveal, however, an epidemic of reasoning taking the following form:

  1. In the present study, when task comparison A was presented, brain area Z was active.
  2. In other studies, when cognitive process X was putatively engaged, then brain area Z was active.
  3. Thus, the activity of area Z in the present study demonstrates engagement of cognitive process X by task comparison A.

This is a ‘reverse inference’, in that it reasons backwards from the presence of brain activation to the engagement of a particular cognitive function.

Reverse inferences are not a valid from of deductive reasoning, because there might be other cognitive functions that activate the brain area. Nevertheless, the general form of reasoning can provide useful information, especially when the function of the particular brain area is relatively specific and particularly well-understood. Using accumulated knowledge to interpret new findings is necessary for theory building. However, in the asbence of a strict one-to-one mapping between structure and function, reverse inference is best approached from a Bayesian perspective rather than a logical inference.

Summary: fMRI is one of the most popular methods in cognitive neuroscience, and certainly the most headline grabbing. fMRI provides unparalleled access to the patterns of brain activity underlying human perception, memory and action; but like any method, there are important limitations. To appreciate these limits, it is important understand some of the basic principles of fMRI. We also need to consider fMRI as part of a broader landscape of available techniques, each with their unique strengths and weakness (figure 6). The question is not so much: is fMRI useful? But rather: is fMRI the right tool for my particular question.

Fig 6. from Sejnowski, Churchland and Movshon, 2014, Nature Neuroscience

Further reading:

CBUImaging wiki

FMRIB

Oxford Sparks (see below for video demo)

UCSD

Neurologism

Neuroskeptic

Key references:

Logothetis, N. K. (2008). What we can do and what we cannot do with fMRI. Nature, 453(7197), 869-878. doi: DOI 10.1038/nature06976

Sejnowski, T. J., Churchland, P. S., & Movshon, J. A. (2014). Putting big data to good use in neuroscience. Nat Neurosci, 17(11), 1440-1441.

Fun demonstration from Oxford Sparks:

Center for Cognitive Medicine at Vanderbilt University Medical Center

What is an fMRI?

Functional MRI or functional Magnetic Resonance Imaging (fMRI) is a type of specialized MRI scan and one of the most r ecently developed forms of brain imaging. It is based on the same technology as the MRI — a noninvasive test that uses a strong magnetic field and radio waves to create detailed images of the body. Instead of creating images of organs and tissues like MRI, an fMRI looks at blood flow in the brain to detect areas of activity. These changes in blood flow, which are captured on a computer and shown on the screen, help doctors and researchers understand more about how the brain works.

This neuroimaging technique allows us to detect the specific areas of the brain which are involved in a task, a process, or an emotion. Color changes on the fMRI scans show researchers what specific parts of the brain are being activated while the person in the scanner responds to images, sounds, or performs various tasks. This ability to see not only the structure of the brain, but the function of the brain is a major scientific advancement in medicine.

What will it be like in the scanner?

During the testing, you will lie on a table. Your head may be placed in a brace to hold it still. Then you are moved into the large, cylindrical MRI machine. You may be given earplugs to reduce the sound, since the scanner can tend to be noisy.

While the machine is scanning your brain, you will be asked to perform a variety of tasks. While remaining still in the scanner, you will use your fingers to give answers on a keyboard. You can expect to be in the scanner for about one hour.

Is it safe?

Developed in the early 1990s, fMRI has come to dominate the brain mapping field due to its non-invasiveness, absence of radiation exposure, and relatively wide availability.

Although an fMRI test doesn’t use radiation, its strong magnetic field and radio waves may not be recommended for certain groups of people including: people with certain types of metal in their bodies (pins, screws, plates or surgical staples for example), people who are particularly claustrophobic, have cochlear implants, pacemakers, or are pregnant. You will be asked to give specific information about these and other possible exclusions prior to being placed in the scanner. All metallic objects (jewelry, pens, etc.) must be removed before entering the MRI suite.

What is fMRI?

Imaging Brain Activity

Courtesy of Dr. David Shin, UC San Diego

In your brain the activity of the neurons constantly fluctuates as you engage in different activities, from simple tasks like controlling your hand to reach out and pick up a cup of coffee to complex cognitive activities like understanding language in a conversation. The brain also has many specialized parts, so that activities involving vision, hearing, touch, language, memory, etc. have different patterns of activity. Even when you rest quietly with your eyes closed the brain is still highly active, and the patterns of activity in this resting state are thought to reveal particular networks of areas that often act together. Functional magnetic resonance imaging (fMRI) is a technique for measuring and mapping brain activity that is noninvasive and safe. It is being used in many studies to better understand how the healthy brain works, and in a growing number of studies it is being applied to understand how that normal function is disrupted in disease.

Magnetic Resonance Imaging (MRI)

Courtesy of Dr. Richard Buxton, UC San Diego

MRI has become a standard tool for Radiology because it provides high resolution images with good contrast between different tissues. It works by exploiting the fact that the nucleus of a hydrogen atom behaves like a small magnet. Using the phenomenon of nuclear magnetic resonance (NMR), the hydrogen nuclei can be manipulated so that they generate a signal that can be mapped and turned into an image. When you lay in the strong magnetic field of an MRI system all of the hydrogen nuclei in your body, most of which are in water molecules, tend to align with that magnetic field. When a radio frequency (RF) magnetic pulse is applied at the right frequency, these hydrogen nuclei absorb energy and then create a brief, faint signal (the MR signal) that is detected by the RF coils in the MRI system.

The MR image is a map of the distribution of the MR signal, and by manipulating the timing of the RF pulses and the delays before detecting the signal MRI is a sensitive tool for detecting subtle changes in brain anatomy. However, mapping brain structure is not the same as mapping brain function.

fMRI

Fox MD, Raichle ME. Spontaneous fluctuations in brain activity
observed with functional magnetic resonance imaging.
Net Rev Neurosci. 2007 Sep;8(9);700-11.

The discovery that MRI could be made sensitive to brain activity, as well as brain anatomy, is only about 20 years old. The essential observation was that when neural activity increased in a particular area of the brain, the MR signal also increased by a small amount. Although this effect involves a signal change of only about 1%, it is still the basis for most of the fMRI studies done today.

In the simplest fMRI experiment a subject alternates between periods of doing a particular task and a control state, such as 30 second blocks looking at a visual stimulus alternating with 30 second blocks with eyes closed. The fMRI data is analyzed to identify brain areas in which the MR signal has a matching pattern of changes, and these areas are taken to be activated by the stimulus (in this example, the visual cortex at the back of the head).

Why is the MR Signal Sensitive to Changes in Brain Activity?

Courtesy of Dr. Richard Buxton, UC San Diego

It is not because the MR signal is directly sensitive to the neural activity. Instead, the MR signal change is an indirect effect related to the changes in blood flow that follow the changes in neural activity. The picture of what happens is somewhat subtle, and depends on two effects. The first effect is that oxygen-rich blood and oxygen-poor blood have different magnetic properties related to the hemoglobin that binds oxygen in blood. This has a small effect on the MR signal, so that if the blood is more oxygenated the signal is slightly stronger. The second effect relates to an unexpected physiological phenomenon. For reasons that we still do not fully understand, neural activity triggers a much larger change in blood flow than in oxygen metabolism, and this leads to the blood being more oxygenated when neural activity increases. This somewhat paradoxical blood oxygenation level dependent (BOLD) effect is the basis for fMRI.

Blood Flow Dynamics Provides a Sensitive Window on Brain Function

Blood flow to an area of the brain is remarkably sensitive to changes in neural activity. If you sequentially tap each finger of one hand against the thumb as fast as you can, the blood flow in the motor region increases by about 60%. For this reason, blood flow changes are a sensitive indicator of underlying neural activity changes. However, these large blood flow fluctuations still result in a BOLD signal change that is only a few percent. Nevertheless, this makes it possible to map changes in activity associated with a wide range of motor, sensory and cognitive tasks. By carefully designing experiments to probe different aspects of brain function, many investigators are trying to better understand the neurological and psychological changes associated with Alzhemer’s disease, schizophrenia, depression, autism and many other disorders.

In addition, in recent years it has become clear that there is a great deal of information on how the brain is organized just in the way different brain regions continue to fluctuate together even when you are not doing a particular task. The strength of these resting state networks (RSN) also changes with disease, and an important goal is to investigate whether psychiatric disease can be understood in terms of disorders of these basic networks.

Measuring Blood Flow Directly with ASL

Courtesy of Dr. Eric Wong, UC San Diego

The BOLD signal that underlies most fMRI applications is essentially a qualitative signal, because it depends in a complex way on the combined physiological changes of blood flow and oxygen metabolism. An alternative MRI method called arterial spin labeling (ASL) is a tool for measuring blood flow changes directly. One of the limitations of the BOLD signal is that it is always a signal change between two conditions, such as tapping your fingers compared to resting. For this reason, BOLD imaging can tell us nothing about the actual level of blood flow before the task started. With ASL it is possible to measure the absolute level of blood flow in any condition. For example, if blood flow decreases as Alzheimer’s disease develops, this could be detected with ASL methods but not with BOLD imaging. ASL works by manipulating the MR signal of arterial blood before it is delivered to different areas of the brain. By subtracting two images in which the arterial blood is manipulated differently, the static signal from all the hydrogen nuclei in the rest of the tissue subtracts out, leaving just the signal arising from the delivered arterial blood.

ASL and BOLD imaging can be used together to provide a more quantitative probe of brain function, including assessment of oxygen metabolism changes, and this potential synergy is a primary motivation for ongoing research at the CFMRI in developing the next generation of fMRI methods.

Diffusion Tensor Imaging (DTI)

Courtesy of Dr. Lawrence Frank, UC San Diego

Brain function depends on the wiring between brain regions, the complex web of axons carrying signals from one neuron to another. In addition to methods for detecting brain activation with fMRI, MRI also provides a way to measure these anatomical connections. The white matter of the brain consists of bundles of these axonal fibers, so that within a small region the fibers are all aligned, and diffusion tensor imaging (DTI) is able to measure the direction of this alignment. Knowing the orientation of the fibers at each point it is possible to trace paths through the brain that map the fiber tracts. The method exploits the sensitivity of the magnetic resonance signal to the small random motions of water molecules. This diffusion of water molecules is analogous to a drop of ink slowly expanding in a pool of water as the ink molecules diffuse. In white matter fiber tracts the displacements of water molecules due to diffusion are much greater along the direction of the fibers than in a perpendicular direction, making it possible to map the fiber orientation with DTI. In addition to mapping white matter fiber tracts, these methods are useful for detecting and characterizing disorders of white matter in disease.

MR Microscopy

Courtesy of Dr. Miriam Scadeng, UC San Diego

Using our 7 Tesla scanner and special purpose coils designed for high resolution imaging, it is possible to image mice (and even zebrafish) with a resolution well below one tenth of a millimeter. While many of these studies also target the brain, these studies also extend outside the brain and include detailed identification of anatomical structures (such as the airways of the mouse lung in this image) for a variety of experiments. The insights into anatomy and physiology made possible by high resolution imaging in small animals provides a critical complement to the human studies on our 3 Tesla scanners.

Structural/Anatomical MRI

Structural MRI provides information about brain anatomy to complement functional MRI in a number of ways. Since brain function depends to some extent on the integrity of brain structure, measures that characterize the underlying tissue integrity allow one to examine the impact of tissue loss or damage on functional signals. Furthermore, structural MRI provides anatomical reference for visualization of activation patterns and regions of interest to extract functional signal information.

Many pulse sequences are available, emphasizing different aspects of normal and abnormal brain tissue. By modifying sequence parameters such as repetition time (TR) and echo time (TE), for example, anatomical images can emphasize contrast between gray and white matter (e.g., T1-weighted with short TR and short TE) or between brain tissue and cerebrospinal fluid (e.g., T2-weighted with long TR and long TE).

Information from structural MRI can be used to describe the shape, size, and integrity of gray and white matter structures in the brain. Morphometric techniques measure the volume or shape of gray matter structures, such as subcortical nuclei or the hippocampus, and the volume, thickness, or surface area of the cerebral neocortex. The volume of normal and abnormal white matter also can allow inference of macrostructural white matter integrity, providing indications of inflammation, edema, and demyelination; complementary microstructural studies using diffusion imaging can help to provide a more comprehensive picture of white matter integrity.

Combining structural MRI, functional MRI and diffusion imaging may more broadly characterize normal and abnormal brain function, supporting biomarker studies of neurodegenerative or psychiatric disorders to determine risk, progression, and therapeutic effectiveness.

Magnetic resonance imaging (MRI), also known as nuclear magnetic resonance imaging, is a scanning technique for creating detailed images of the human body.

The scan uses a strong magnetic field and radio waves to generate images of parts of the body that can’t be seen as well with X-rays, CT scans or ultrasound. For example, it can help doctors to see inside joints, cartilage, ligaments, muscles and tendons, which makes it helpful for detecting various sports injuries.

MRI is also used to examine internal body structures and diagnose a variety of disorders, such as strokes, tumors, aneurysms, spinal cord injuries, multiple sclerosis and eye or inner ear problems, according to the Mayo Clinic. It is also widely used in research to measure brain structure and function, among other things.

“What makes MRI so powerful is, you have really exquisite soft tissue, and anatomic, detail,” said Dr. Christopher Filippi, a diagnostic radiologist at North Shore University Hospital, Manhasset, New York. The biggest benefit of MRI compared with other imaging techniques (such as CT scans and x-rays) is, there’s no risk of being exposed to radiation, Filippi told Live Science.

What to expect

During an MRI, a person will be asked to lie on a movable table that will slide into a doughnut-shaped opening of the machine to scan a specific portion of your body. The machine itself will generate a strong magnetic field around the person and radio waves will be directed at the body, according to the Mayo Clinic.

A person will not feel the magnetic field or radio waves, so the procedure itself is painless. However, there may be a lot of loud thumping or tapping noises during the scan (it may sound like a sledgehammer!), so people are often given headphones to listen to music or earplugs to help block the sound. A technician may also give instructions to you during the test.

Some people may be given a contrast solution by intravenous, a liquid dye that can highlight specific problems that might not show up otherwise on the scan.

Young children as well as people who feel claustrophobic in enclosed places may be given sedating medication to help them relax or fall asleep during the scan because it is important to stay as still as possible to get clear images. Movement can blur the images.

Some hospitals might have an open MRI machine that is open on the sides rather than the tunnel-like tube found in a traditional machine. This may be a helpful alternative for people who feel afraid of confined spaces.

The scan itself may take 30 to 60 minutes, on average, according to the American Academy of Family Physicians.

A radiologist will look at the images and send a report to your doctor with your test results.

How it works

The human body is mostly water. Water molecules (H2O) contain hydrogen nuclei (protons), which become aligned in a magnetic field. An MRI scanner applies a very strong magnetic field (about 0.2 to 3 teslas, or roughly a thousand times the strength of a typical fridge magnet), which aligns the proton “spins.”

The scanner also produces a radio frequency current that creates a varying magnetic field. The protons absorb the energy from the magnetic field and flip their spins. When the field is turned off, the protons gradually return to their normal spin, a process called precession. The return process produces a radio signal that can be measured by receivers in the scanner and made into an image, Filippi explained.

An MRI scan reveals the gross anatomical structure of the human brain. (Image credit: Courtesy FONAR Corporation)

Protons in different body tissues return to their normal spins at different rates, so the scanner can distinguish among various types of tissue. The scanner settings can be adjusted to produce contrasts between different body tissues. Additional magnetic fields are used to produce 3-dimensional images that may be viewed from different angles. There are many forms of MRI, but diffusion MRI and functional MRI (fMRI) are two of the most common.

Diffusion MRI

This form of MRI measures how water molecules diffuse through body tissues. Certain disease processes — such as a stroke or tumor — can restrict this diffusion, so this method is often used to diagnose them, Filippi said. Diffusion MRI has only been around for about 15 to 20 years, he added.

Functional MRI

In addition to structural imaging, MRI can also be used to visualize functional activity in the brain. Functional MRI, or fMRI, measures changes in blood flow to different parts of the brain.

It is used to observe brain structures and to determine which parts of the brain are handling critical functions. Functional MRI may also be used to evaluate damage from a head injury or Alzheimer’s disease. fMRI has been especially useful in neuroscience — “It has really revolutionized how we study the brain,” Filippi told Live Science.

MRI safety

Unlike other imaging forms like X-rays or CT scans, MRI doesn’t use ionizing radiation. MRI is increasingly being used to image fetuses during pregnancy, and no adverse effects on the fetus have been demonstrated, Filippi said.

Still, the procedure can have risks, and medical societies don’t recommend using MRI as the first stage of diagnosis.

Because MRI uses strong magnets, any kind of metal implant, such as a pacemaker, artificial joints, artificial heart valves, cochlear implants or metal plates, screws or rods, pose a hazard. The implant can move or heat up in the magnetic field.

Several patients with pacemakers who underwent MRI scans have died, patients should always be asked about any implants before getting scanned. Many implants today are “MR-safe,” however, Filippi said.

The constant flipping of magnetic fields can produce loud clicking or beeping noises, so ear protection is necessary during the scan.

Cari Nierenberg contributed to this article.

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