Measuring Blood Oxygenation in the Brain Functional Imaging • Functional Imaging must provide a spatial depiction of some process that is at least indirectly related to neural activity • in most imaging (i.e. PET, fMRI) that process is change in blood oxygenation related to changes in regional cerebral blood flow • Why should we measure blood oxygenation? Functional Imaging • Why should we measure blood oxygenation? • Onset of a stimulus (or cognitive task) changes local blood oxygenation – first with a decrease – then with an “overshoot” Functional Imaging • Why should we measure blood oxygenation? • Onset of a stimulus (or cognitive task) changes local blood oxygenation – first with a decrease – then with an “overshoot” • How do we measure changes in blood oxygenation? Functional Imaging • Recall that precessing protons give off a radio “echo” as they realign with the magnetic field Functional Imaging • Recall that precessing protons give off a radio “echo” as they realign with the magnetic field • We pick up the combined echo from many protons that are in phase Functional Imaging • recall that the precession frequency depends on the field strength – anything that changes the field at one proton will cause it to dephase Functional Imaging • recall that the precession frequency depends on the field strength – anything that changes the field at one proton will cause it to dephase • The de-phased region will give off less echo Functional Imaging • Oxygenated hemoglobin is diamagnetic - it has no magnetic effects on surrounding molecules • Deoxygenated hemoglobin is paramagnetic - it has strong magnetic effects on surrounding molecules! QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Hemoglobin Heme Functional Imaging • Oxygenated hemoglobin is diamagnetic - it has no magnetic effects on surrounding molecules • Deoxygenated hemoglobin is paramagnetic - it has strong magnetic effects on surrounding molecules! • Thus deoxygenated tissue gives of less MR echo because the protons de-phase quickly Functional Imaging • blood flow overshoots baseline after a brain region is activated • More oxygenated blood in that region increases MR signal from that region (other regions de-phase faster) Functional Imaging • It is important to recognize that fMRI “sees” changes in the ratio of oxygenated to deoxygenated blood nothing more – BOLD: Blood Oxygenation Level Dependant contrast • How do we create those pretty pictures? Functional Imaging • It is important to recognize that fMRI “sees” changes in the ratio of oxygenated to deoxygenated blood nothing more – BOLD: Blood Oxygenation Level Dependant contrast • How do we create those pretty pictures? • We ask the question “When the subject engages in this cognitive task, where does blood oxygenation change significantly?” “where does it change randomly?” Experimental Design in fMRI • Experimental Design is crucial in using fMRI • Simplest design is called “Blocked” – alternates between active and “rest” conditions Active 60 sec Rest 60 sec Active 60 sec Rest 60 sec Experimental Design in fMRI • Experimental Design is crucial in using fMRI • Simplest design is called “Blocked” – alternates between active and “rest” conditions QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Experimental Design in fMRI Signal • A voxel in tissue insensitive to the task demands shows random signal change QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Experimental Design in fMRI Signal • A voxel in tissue that responds to the task shows signal change that matches the timecourse of the stimulus QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Active 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Rest 60 sec QuickTime™ and a decompressor are needed to see this picture. QuickTime™ and a decompressor are needed to see this picture. Experimental Design in fMRI • A real example of fMRI design done well: – alternate moving, blank and stationary visual input Moving 40 sec Blank 40 sec Stationary 40 sec Blank 40 sec Experimental Design in fMRI • Voxels in Primary cortex tracked all stimuli QuickTime™ and a decompressor are needed to see this picture. Experimental Design in fMRI • Voxels in area MT tracked only the onset of motion QuickTime™ and a decompressor are needed to see this picture. Experimental Design in fMRI • Voxels in area MT tracked only the onset of motion • How did they know to look in area MT? QuickTime™ and a decompressor are needed to see this picture. PET: another way to measure blood Oxygenation • Positron Emission Tomography (PET) • Injects a radioisotope of oxygen • PET scanner detects the concentration of this isotope as it decays QuickTime™ and a decompressor are needed to see this picture. PET: another way to measure blood Oxygenation • Although oxygenation is measured differently, the logic of PET and fMRI are similar: compare active and “rest” conditions Advantages of fMRI • All techniques have certain advantages • A good scientist leverages these advantages Advantages of fMRI • Advantages of MRI: 1. Most hospitals have MRI scanners that can be used for fMRI (PET is rare) 2. Better spatial resolution in fMRI than PET 3. Structural MRI is usually needed anyway 4. No radioactivity in MRI 5. Better temporal resolution in MRI Advantages of PET • Advantages of PET: 1. Quiet 2. A number of different molecules can be labeled and imaged in the body Limitations of fMRI • All techniques have constraints and limitations • A good scientist is careful to interpret data within those constraints Limitations of fMRI • Limitations of MRI and PET: 1. BOLD signal change does not necessarily mean a region was specifically engaged in a cognitive operation 2. Poor temporal resolution - depends on slow changes in blood flow 3. expensive
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