Functional MRI CS 689 Computational Medical Imaging Processing

Functional MRI CS 689 Computational Medical Imaging Processing Spring 2007 University of Kentucky

Outline 1. 2. 3. 4. 5. f. MRI vs. MRI Procedures of f. MRI Medical Significance of f. MRI Methods of f. MRI Types of f. MRI 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 2 • .

a Simple Definition: If the MRI experiment is done while a mental task is given to a subject, a so-called functional magnetic resonance image (f. MRI) is generated. f. MRI is used to map different sensor, motor and cognitive functions to specific regions in the brain. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 3 • .

f. MRI vs. MRI studies brain anatomy. Seeing brain structure 3 Dbrain anatomy 4/3/2007 University of Kentucky Functional MRI (f. MRI) studies brain function. CS 689 Computational Medical Imaging Processing • 4 • .

Procedures of f. MRI 1. 2. 3. 4. 5. a series of baseline images are taken of the brain region of interest when the subject is at rest, as A the subject performs a task a second series of images is taken, as A’ the first set of images is subtracted from the second, as B=A’-A the areas that are most visible in the resulting image, B, are presumed to have been activated by the task. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 5 • .

One example Visual cortex Auditory cortex n A healthy subject was asked to listen to sentences being spoken while watching a screen with a flashing checkerboard presented. The sentences started and stopped at slightly different times than the flashing picture was turned on and off. 4/3/2007 University of Kentucky n On the basis of the differences in timing activation in the brain, the areas responsible for hearing (in the middle of the brain in grey) and vision (in the back of the brain in white) could be localized by f. MRI (Image courtesy of Dr. S. Smith from www. fmrib. ox. ac. uk). CS 689 Computational Medical Imaging Processing • 6 • .

a Experiment n Timing: q q It consists of a set of trials, and the data is partitioned into trials. For some of these intervals, the subject simply rested, or gazed at a fixation point on the screen. For other trials, the subject was shown a picture and a sentence, and instructed to press a button to indicate whether the sentence correctly described the picture. For these trials, the sentence and picture were presented in sequence, with the picture presented first on half of the trials, and the sentence presented first on the other half of the trials. Forty such trials are available for each subject. The timing within each such trial is as follows: 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 7 • .

n The first stimulus (sentence or picture) was presented at the begining of the trail (image=1). n 4 seconds later (image=9) the stimulus was removed, replaced by a blank screen. n 4 seconds later (image=17) the second stimulus was presented. This remained on the screen for 4 seconds, or until the subject pressed the mouse button, whichever came first. n A rest period of 15 seconds (30 images) was added after the second stimulus was removed from the screen. Thus, each trial lasted a total of approximately 27 seconds (approximately 54 images). n Imaging parameters: Images were collected every 500 msec. Only a fraction of the brain of each subject was imaged. The data is marked up with 25 -30 anatomically defined regions (called "Regions of Interest", or ROIs). 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 8 • .

Medical Significance of f. MRI n Different tasks activate different parts of the brain q n When listening to music, a specialized area in the auditory cortex along the sides of the brain shows an increased signal The locations vary for different cases and individuals. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 9 • .

Medical Significance of f. MRI a diagnostic method n q q learning how a normal, diseased or injured brain is working assessing the potential risks of surgery or other invasive treatment of the brain. planning brain surgery -- monitor normal brain function as well as any disturbed brain function. While research is still ongoing, it appears that f. MRI can also help assess the effects of stroke, trauma or degenerative disease (such as Alzheimer's) on brain function. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 10 • .

f. MRI? n It aims to determine the neurobiological correlation of behavior by identifying the brain regions (or “functioning modules”) that become “active” during the performance of specific tasks in vivo. n It extends traditional anatomical imaging to functional imaging. q q observe both the structures and which structures participate in specific functions improving our understanding of a variety of brain pathologies. n such as the addictive behaviors of gambling or drug abuse, are without structural brain changes. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 11 • .

the principle: n when a brain region is being used, arterial oxygenated blood will redistribute and increase to this area. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 12 • .

Knowledge required n The science of applying f. MRI is quite complicated and multidisciplinary. It involves: q q q Physics: Statistics: Because the signals are very subtle, correct application of statistics is essential in the statistical analysis of results to "tease out" observations and avoid false-positive results. Psychology: When conducting f. MRI on humans it is essential to employ carefully designed psychophysical experiments which allow the precise measurement of the neural effect under consideration. Neuroscience: For a non-invasive scan, MRI has moderately good spatial resolution, but relatively poor temporal resolution. Increasingly, it is being combined with other data collection techniques such as electroencephalography (EEG) or magnetoencephalography (MEG), which have much higher recording frequencies. Neuroanatomy: Anatomy is critical in understanding the location (and role) of the signals which f. MRI is able to detect. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 13 • .

3. Types of functional MRI: n BOLD f. MRI q n perfusion f. MRI q n Measures blood oxygenation, i. e, regional differences in oxygenated blood measures regional cerebral blood flow, i. e. the rate at which blood is delivered to tissue. diffusion-weighted f. MRI q q measures random movement of water molecules in tissue. It can detect acute brain infarction within 1 to 2 hours ***Infarct: 梗塞, 如由于血栓或栓子的原因，局部血液供应不畅而引发局部组织坏死 n Magnetic Resonance Spectroscopic Imaging (MRSI) q q measure certain cerebral metabolites noninvasively. phase encoding is used to obtain spectra from multiple regions across a field of view. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 14 • .

3. 1 BOLD f. MRI n n Blood Oxygen Level Dependent Contrast Based on: q (1) different magnetic properties of deoxy- and oxyhemoglobin (氧合血红蛋白) q n n n (2) coupling of oxygenated blood flow and neuronal activity High spatial and temporal resolution 3 -6 second delay in hemodynamic(血液动力学) response ---limits optimal temporal resolution. Compares images taken during active and rest states within a single session 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 15 • .

MRI vs. f. MRI high resolution (1 mm) MRI f. MRI low resolution (~3 mm but can be better) one image f. MRI Blood Oxygenation Level Dependent (BOLD) signal indirect measure of neural activity … many images (e. g. , every 2 sec for 5 mins) blood oxygen f. MRI signal 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 16 • .

Slice Terminology VOXEL (Volumetric Pixel) Slice Thickness e. g. , 6 mm In-plane resolution e. g. , 192 mm / 64 = 3 mm SAGITTAL SLICE IN-PLANE SLICE 6 mm 3 mm Number of Slices e. g. , 10 Matrix Size e. g. , 64 x 64 Field of View (FOV) e. g. , 19. 2 cm 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 17 • .

Hemoglobin Figure Source, Huettel, Song & Mc. Carthy, 2004, Functional Magnetic Resonance Imaging 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 18 • .

Magnetic properties of deoxy- and oxyhaemoglobin n Deoxyhaemoglobin is paramagnetic n The presence of deoxyhaemoglobin in vessel causes a susceptibility difference between the vessel and its surrounding tissue. Then causes dephasing of MR proton signal Leading to a reduction in the value of T 2*, which causes a darkening of the image n n n oxyhaemoglobin is diamagnetic 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 19 • .

Susceptibility artifacts The magnetic susceptiblity of a material : : a measure of how much magnetization is produced within it when it is placed in a magnetic field. q q q Susceptibility differences between tissues can lead to signal loss in MR scans, especially in EPI scans. The susceptibility difference between deoxygenated and oxygenated blood is the basis of the BOLD effect used to detect f. MRI signals. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 20 • .

HDR (Hemodynamics Response) n n the time courses of the changes in blood flow, blood volume and blood oxygenation that occur in the brain in response to brain activity. In the brain, neuronal activity is thought to cause a local increase in blood flow (CBF), which leads to an increase in blood oxygenation and blood volume (CBV). Upon activation, oxygen is extracted by the cells, increasing the level of deoxyhaemoglobin in the blood. And it is compensated for by an increase in blood flow in the vicinity of the active cells, leading to a net increase in oxyhaemoglobin. Signal changes 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 21 • .

T 2*-weighted imaging n T 2*-weighted images are performed which take advantage of the different magnetic properties of deoxyand oxyhaemoglobin. n Because of the magnetic properties of the deoxyhaemoglobin molecule which causes rapid dephasing, T 2* signal is retained longer in a region when it has more oxygenated blood compared to when there is less oxygenated blood. n Thus, an area with more oxygenated blood will show up more intense on T 2*-weighted images compared to when there is less oxygenated blood around. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 22 • .

BOLD Time Course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 23 • .

Evolution of BOLD Response Hu et al. , 1997, MRM 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 24 • .

Initial Dip (Hypo-oxic Phase) n n n Transient increase in oxygen consumption, before change in blood flow q Menon et al. , 1995; Hu, et al. , 1997 Smaller amplitude than main BOLD signal q 10% of peak amplitude (e. g. , 0. 1% signal change) Potentially more spatially specific q Oxygen utilization may be more closely associated with neuronal activity than positive response Slide modified from Duke course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 25 • .

Rise (Hyperoxic Phase) n n Results from vasodilation of arterioles, resulting in a large increase in cerebral blood flow Inflection point can be used to index onset of processing Slide modified from Duke course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 26 • .

Peak – Overshoot n n Over-compensatory response q More pronounced in BOLD signal measures than flow measures Overshoot found in blocked designs with extended intervals q Signal saturates after ~10 s of stimulation Slide modified from Duke course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 27 • .

Sustained Response n n Blocked design analyses rest upon presence of sustained response q Comparison of sustained activity vs. baseline q Statistically simple, powerful Problems q Difficulty in identifying magnitude of activation q Little ability to describe form of hemodynamic response q May require detrending of raw time course Slide modified from Duke course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 28 • .

Undershoot n n Cerebral blood flow more locked to stimuli than cerebral blood volume q Increased blood volume with baseline flow leads to decrease in MR signal More frequently observed for longer-duration stimuli (>10 s) q Short duration stimuli may not evidence q May remain for 10 s of seconds Slide modified from Duke course 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 29 • .

BOLD = convolution BOLD f. MRI of neuronal activity and n haemodynamic transfer function (gamma) Neuronal Activity BOLD Signal Haemodynamic Function Time Slide from Matt Brown 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 30 • .

BOLD Summates Neuronal Activity Slide from Matt Brown 4/3/2007 University of Kentucky BOLD Signal CS 689 Computational Medical Imaging Processing • 31 • .

BOLD Overlap and Jittering n n Burock et al. 1998. 4/3/2007 University of Kentucky Closely-spaced haemodynamic impulses summate. Constant ITI causes tetanus. CS 689 Computational Medical Imaging Processing • 32 • .

Design Types = trial of one type (e. g. , face image) = trial of another type (e. g. , place image) = null trial (nothing happens) Block Design Slow ER Design Rapid Counterbalanced ER Design Rapid Jittered ER Design Mixed Design 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 33 • .

* Example A typical BOLD time course with 4 “active” states and 4 “resting” states. n n With prior knowledge of the activation timing, we can perform a statistical test on the data to determine which areas of the brain are active, then overlay this statistical map (shown in color) on a high resolution MR image so that one can visualize the functional information in relation to relevant anatomical landmarks. There a wide variety of different software packages that facilitate processing, analysis and display of f. MRI data in addition to many different stimulus delivery packages: http: //www. fmri-world. de/ The choice of each depends largely on the onsite resources and the specific application. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 34 • .

* Functional mapping : Statistical Parametric Mapping n Statistical parametric mapping entails the construction of spatially extended statistical processes to test hypotheses about regionally specific effects (Friston et al. 1991). n image processes with voxel values that are distributed according to a known probability density function, usually T or F distributions. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 35 • .

General Linear Model (GLM) n To estimate some parameters that could explain the spatially continuous data in exactly the same way as in conventional analysis of discrete data. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 36 • .

Gaussian random field n GRF theory is used to resolve the multiplecomparisons problem that ensues when making inferences over a volume of the brain. n GRF theory provides a method for adjusting p values for the search volume of an SPM to control false positive rates. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 37 • .

Bayesian inferences n Bayesian inferences about spatially extended effects use posterior probability maps (PPMs). 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 38 • .

* Two issues on BOLD f. MRI n No prior knowledge of activation timing n Temporal limits : HDR delay n Spatial limits of f. MRI 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 39 • .

1. When the temporal response is unknown… n new f. MRI analysis methods to detect activation without prior knowledge of activation timing. n One of these methods is called Independent Component Analysis (ICA) n It involves the development of novel ICA algorithms that are specific to f. MRI data, the development of new stimulus designs that are appropriate for ICA and the use of ICA in patient populations to remove noise and motion artifacts. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 40 • .

2. HDR delay & Limited temporal resolution n A time delay from the onset of the neural activity to the change of BOLD signal. q q a time delay of 3 -6 seconds between when a brain region is activated and blood flow increases to it. During this time, the activated areas experience a relative decrease in oxygenated blood as oxygen is extracted by the active regional neurons. Afterward, the amount of blood flowing to the area far outweighs the amount of oxygen that is extracted so that oxygenated blood is now higher. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 41 • .

Limited temporal resolution n Although images can be acquired every 100 msecs with EPI, this predictable but time-varied delayed onset of the BOLD response limits the immediate temporal resolution to several seconds instead of the 100 msec. n In the future, researchers may be able to improve the temporal resolution of f. MRI by measuring the initial decrease in oxygenated blood with activation. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 42 • .

3. What Limits Spatial Resolution n n noise q smaller voxels have lower SNR head motion q the smaller your voxels, the more contamination head motion induces temporal resolution q the smaller your voxels, the longer it takes to acquire the same volume n 4 mm x 4 mm at 16 slices/sec OR 1 mm x 1 mm at 1 slice/sec vasculature q depends on pulse sequences n e. g. , spin echo sequences reduce contributions from large vessels q some preprocessing techniques may reduce contribution of large vessels (Menon, 2002, MRM) 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 43 • .

The Initial Dip n n The initial dip seems to have better spatial specificity However, it’s often called the “elusive initial dip” for a reason 4/3/2007 University of Kentucky CS 689 f. MRI for Dummies Computational Medical Imaging Processing • 44 • .

Voxelnon-isotropic Size non-isotropic 3 x 3 x 6 = 54 mm 3 3 x 3 x 3 = 27 mm 3 2. 1 x 6 = 27 mm 3 e. g. , SNR = 100 e. g. , SNR = 71 In general, larger voxels buy you more SNR. EXCEPT when the activated region does not fill the voxel (partial voluming) 4/3/2007 University of Kentucky CS 689 f. MRI for Dummies Computational Medical Imaging Processing • 45 • .

Partial Voluming n n The f. MRI signal occurs in gray matter (where the synapses and dendrites are) If your voxel includes white matter (where the axons are), fluid, or space outside the brain, f. MRI for Dummies CS 689 your Computational Medical Imaging Processing you effectively down signal 4/3/2007 University ofwater Kentucky • 46 • .

Partial Voluming Partial volume effects: The combination, within a single voxel, of signal contributions from two or more distinct tissue types or functional regions (Huettel, Song & Mc. Carthy, 2004) This voxel contains mostly gray matter This voxel contains mostly white matter This voxel contains both gray and white matter. Even if neurons within the voxel are strongly activated, the signal may be washed out by the absence of activation in white matter. Partial voluming becomes more of a problem with larger voxel sizes Worst case scenario: A 22 cm x 22 cm voxel would contain the whole brain 4/3/2007 University of Kentucky CS 689 f. MRI for Dummies Computational Medical Imaging Processing • 47 • .

3. 2. Diffusion and Perfusion MRI n Diffusion MRI measures the molecular mobility of water in tissue, while perfusion MRI measures the rate at which blood is delivered to tissue. n Therefore, both these techniques measure quantities which have direct physiological relevance. n Diffusion in biological systems is a complex phenomenon, influenced directly by tissue microstructure, and that its measurement can provide a large amount of information about the organization of this structure in normal and diseased tissue. n Perfusion reflects the delivery of essential nutrients to tissue, and so is directly related to its status. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 48 • .

3. 3. MRS q q Magnetic Resonance Spectroscopy. The data gathered in MRS is presented as a spectrum. (i. e. the strength of the magnetic resonance signal is plotted as a function of resonant frequency). Because of the way magnetic resonance works, the chemical environment of the nucleus being scanned will vary its resonant frequency. Hence, by observing the position of peaks in MR spectroscopic data it is possible to determine some of the molecules present in the sample. 4/3/2007 University of Kentucky CS 689 Computational Medical Imaging Processing • 49 • .