Jody Culham Brain and Mind Institute Department of Psychology Western University http://www.fmri4newbies.com/ fMRI Physics in a Nutshell Understanding WTF your MR physicist is talking about Last Update: January 14, 2013 Last Course: Psychology 9223, W2013 History of NMR NMR = nuclear magnetic resonance Rabi; Block and Purcell • atomic nuclei absorb and re-emit radio frequency energy nuclear: properties of nuclei of atoms magnetic: magnetic field required resonance: interaction between magnetic field and radio frequency Felix Bloch Edward Purcell NMR MRI: Why the name change? Most likely explanation: “Nuclear” has bad connotations Less likely but more amusing explanation: Subjects got nervous when fast-talking doctors suggested an NMR History of MRI 1971: Raymond Damadian uses NMR for tumor detection 1972: Lauterbur suggests NMR could be used to form images using gradients 1977: Peter Mansfield proposes echo-planar imaging (EPI) to acquire images faster 1977: first MRI scanner (0.05 T) created by Damadian’s FONAR corporation, named “Indomitable” 1977: First MR image of human body • Didn’t use EPI • Each voxel took 2 min; 106 voxels • 4 hours to get one slice History of fMRI fMRI -1990: Ogawa observes BOLD effect with T2* blood vessels became more visible as blood oxygen decreased -1991: Belliveau observes first functional images using a contrast agent -1992: Ogawa et al. and Kwong et al. publish first functional images using BOLD signal Seiji Ogawa First Functional Images Flickering Checkerboard OFF (60 s) - ON (60 s) - OFF (60 s) - ON (60 s) Source: Kwong et al., 1992 Five Nobels; One Ig Nobel; One Controversy 1944 Nobel • Isador Rabi 1956 Nobel • Felix Bloch and Edward Purcell 2000 Ig Nobel • for discoveries "that cannot, or should not, be reproduced” • Pek van Andel, British Medical Journal 2003 Nobel • Paul Lauterbur and Peter Mansfield • Damadian protests Inside the MRI Scanner Robarts Research Institute 3T Delivery August 2008 The Big Magnet Very strong 1 Tesla (T) = 10,000 Gauss Earth’s magnetic field = 0.5 Gauss 3 Tesla = 3 x 10,000 0.5 = 60,000X Earth’s magnetic field Continuously on Robarts Research Institute Siemens 3T Tim Trio Main field = B0 x 60,000 = B0 MRI Scanner: Three Key Components 3T magnet RF Coil gradient coil (inside) Necessary Equipment Magnet Gradient Coil Source for Photos: Joe Gati Radiofrequency Coil Source for Photo: Siemens Improving Data Quality To get better quality data (higher signal-to-noise, as we’ll discuss later): 1. Increase field strength (e.g., use a 3 T scanner instead of a 1.5 T scanner) and/or 2. Use a coil with more channels (e.g., use a 32channel head coil instead of a 12-channel head coil Coils are Application-Specific 12-channel head coil 32-channel head coil 16-channel breast coil Images from: https://www.medical.siemens.com 8-channel knee coil 16-channel peripheral coil Parallel Imaging Siemens Total Imaging Matrix (Tim) system Coils Head coil Surface coil • homogenous signal • moderate SNR • highest signal at hotspot • high SNR at hotspot Photo source: Joe Gati Phased Array (Parallel Imaging) Coils • • • SNR of surface coils with the coverage of head coils OR… faster parallel imaging modern scanners come standard with 8- or 12-channel head coils and capability for up to 32 channels 12-channel coil 32-channel coil 90-channel prototype Mass. General Hospital Wiggins & Wald 32-channel head coil Siemens Photo Source: Technology Review Phased Array Coils Source: Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging Step 1: Study Atoms With NMR Spin Heads have lots of water, thus lots of protons… Let’s study a head Can measure nuclei with odd number of protons or odd number of neutrons 1H, 13C, 19F, 23Na, 31P 1H hydrogen (proton) abundant: high concentration in human body (5 x 1027 protons in 150 lb guy) high sensitivity: yields large signals 1H = “proton” Less common isotopes have neutrons The most common form (99.98%) of hydrogen has one proton and no neutrons Protons: No Magnetic Field • protons in random orientation (obviously not to scale!) Step 2: Put Subject in Big Magnet Protons (hydrogen atoms) have “spins” (like tops). They have an orientation and a frequency. Protons: Within Magnetic Field B0 • protons align parallel or anti-parallel to B0 (parallel>antiparallel) – actually only 0.0003% of protons/T align with field • phase is random Larmor Frequency Larmor equation f = B0 = 42.58 MHz/T for hydrogen At 1.5T, f = 63.8 MHz At 3T, f = 127.7 MHz At 7T f = 298.1 MHz 298.1 Resonance Frequency for 1H 63.8 1.5 3.0 Field Strength (Tesla) 7.0 Radio Frequency Protons: Within Magnetic Field longitudinal axis z Longitudinal magnetization Mz y Transverse magnetization Mxy B0 sum of red vectors along longitudinal axis Mz > 0 x Now imagine viewing the spins from above sum of red vectors in transverse plane Mxy~0 transverse plane Step 3: Apply Radio Waves longitudinal axis M=~0 z Longitudinal magnetization Mz y B0 sum of red vectors along longitudinal axis Mz ~ 0 90 RF Pulse Transverse magnetization Mxy x Now imagine viewing the spins from above sum of red vectors in transverse plane Mxy > 0 transverse plane Step 4: Measure Radio Waves Measure during recovery period longitudinal axis Longitudinal z magnetization Mz z y Transverse magnetization Mxy x Before 90° pulse z y y transverse plane x x Immediately after 90° pulse Long after 90° pulse • Measure radio waves as protons gradually return to original configuration within the magnetic field Step 4: Measure Radio Waves Goebel (2007) book chapter Step 4: Measure Radio Waves Short T1 (e.g., fat) 1.0 Transverse Magnetization Mxy Longitudinal Magnetization Mz By selecting TR and TE, we can choose T1- vs. T2-weighting Long T1 (e.g., CSF) 0.5 0 Long T2 (e.g., CSF) 1.0 0.5 Short T2 (e.g., fat) 0 0 1 2 3 Time to Repetition = TR (s) 0 100 200 Time to Echo = TE (ms) T1 measures how quickly the protons realign with the main magnetic field T2 measures how quickly the protons give off energy as they recover to equilibrium T1-WEIGHTED ANATOMICAL IMAGE T2-WEIGHTED ANATOMICAL IMAGE Jargon Watch • • • • • T1 = the most common type of anatomical image T2 = another type of anatomical image TR = repetition time = one timing parameter TE = time to echo = another timing parameter flip angle = how much you tilt the protons (90 degrees in example above) Step 5: Use Gradients to Encode Space Remember the Larmor equation: f = B0 higher magnetic field; higher frequencies (The differences aren’t actually this large) B0 gradient gradient of field strength 3.1 T 1H Larmor freq = 132.0 MHz 2.9 T 1H Larmor freq = 123.5 MHz lower magnetic field; lower frequencies Step 5: Use Gradients to Encode Space • We’ve seen how gradients can be used to encode one direction of space (slice selection) • Other gradients and other tricks (frequency encode and phase encode) can be used to encode the other two directions, though it’s more complicated Step 6: Convert Frequencies to Brain Space k-space contains information about frequencies in image We want to see brains, not frequencies The Mona Lisa in K-Space Original Mona Source: Traveler’s Guide to K-space (C.A. Mistretta) • • • low frequencies in centre high frequencies in surround different orientations around the clock The Mona Lisa in K-Space Original Mona Source: Traveler’s Guide to K-space (C.A. Mistretta) Low-Frequency Mona High-Frequency Mona A Walk Through K-space single shot EPI single shot spiral (forgive the hand-drawn spiral) echo-planar imaging • sample k-space in a linear zig-zag trajectory spiral imaging • sample k-space in a spiral trajectory T2 and T2* Dephasing of transverse magnetization due to both: 1. spin-spin interactions (T2) 2. static magnetic field inhomogeneities (additional T2* effects) Mxy spin echo sequences -sensitive to T2 but not T2* effects T2 T2* Source: Adapted from Jorge Jovicich gradient echo sequences -sensitive to T2+T2* effects time Spin Echo Sequence Goebel (2007) book chapter Pulse Sequence • series of excitations, gradient triggers and readouts Gradient echo Echos – refocussing of signal pulse sequence Spin echo: use a 180 degree pulse to “mirror image” the spins in the transverse plane when “fast” regions get ahead in phase, make them go to the back and catch up -measure T2 -ideally TE = average T2 Gradient echo: flip the gradient from negative to positive t = TE/2 A gradient reversal (shown) or 180 pulse (not shown) at this point will lead to a recovery of transverse magnetization Source: Mark Cohen’s web slides make “fast” regions become “slow” and vice-versa -measure T2* -ideally TE ~ average T2* TE = time to wait to measure refocussed spins Magnetic Field Non-uniformities and Shimming Adding a non-uniform object (like a person) to B0 will make the total magnetic field non-uniform Shimming: applying non-uniform shimming gradients to “even out” coarse nonuniformities in the magnetic field If the subject moves after shimming, the magnetic field uniformity may change Barry et al., 2010, MRI Susceptibility Susceptibility: generation of extra magnetic fields in materials that are immersed in an external field sinuses ear canals Susceptibility Artifact -occurs near junctions between air and tissue • sinuses, ear canals -spins become dephased so quickly (quick T2*), no signal can be measured Susceptibility variations can also be seen around blood vessels where deoxyhemoglobin affects T2* in nearby tissue Source: Robert Cox’s web slides Hemoglobin Hemoglogin (Hgb): - can attach up to four oxygen atoms (O2) - oxy-Hgb (four O2) is diamagnetic no B effects - deoxy-Hgb is paramagnetic if [deoxy-Hgb] local B Source: http://wsrv.clas.virginia.edu/~rjh9u/hemoglob.html, Jorge Jovicich BOLD signal Blood Oxygen Level Dependent signal neural activity blood flow oxyhemoglobin T2* MR signal At Rest: Mxy Signal Mo sin T2* task T2* control Stask Scontrol Active: S TEoptimum time Source: Jorge Jovicich Figure Source: Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging MRI Safety Magnetic Fields • main magnetic field is very strong • BUT static magnetic fields are less of a concern than changing magnetic fields • moving quickly through a magnetic field, especially the head, is a BAD idea -- like doing whole brain TMS on yourself • some people experience dizziness, nausea, metallic tastes – BUT these were also reported in 45% of subjects when the magnet was OFF! • typical consent form phrasing: “no known risks” – you can never prove anything is safe, only that something is unsafe Magnet Safety: Big Things Source: www.howstuffworks.com Source: http://www.simplyphysics.com/ flying_objects.html “Large ferromagnetic objects that were reported as having been drawn into the MR equipment include a defibrillator, a wheelchair, a respirator, ankle weights, an IV pole, a tool box, sand bags containing metal filings, a vacuum cleaner, and mop buckets.” -Chaljub et al., (2001) AJR Very Serious Risk Westchester NY, 2001 Source: http://www.mrireview.com/docs/mrideath.pdf Magnet Safety: Little Things Aneurysm clips can be pulled off vessels, leading to death Flying things can kill people. Even in less severe incidents, they can fly into the magnet and damage it or require an expensive shutdown. Subject Safety Anyone going near the magnet – subjects, staff and visitors – must be thoroughly screened: Subjects must have no metal in their bodies: • pacemaker • aneurysm clips • metal implants (e.g., cochlear implants) • interuterine devices (IUDs) • some dental work (but fillings are okay) This subject was wearing a hair band with a ~2 mm copper clamp. Left: with hair band. Right: without. Source: Jorge Jovicich Subjects must remove metal from their bodies • jewellery, watch, piercings • coins, etc. • wallet • any metal that may distort the field (e.g., underwire bra) Females must not be pregnant or at risk of conceiving • Some institutions even require pregancy tests for any female, every session Subjects must be given ear plugs (acoustic noise can reach 120 dB) Fall-off of Magnetic Field Very Serious Risk Source: http://www.fmrib.ox.ac.uk/%7Epeterj/safety_docs/fda_primer.html Magnet Safety 1. 2. 3. 4. 5. Principal Investigators should be sure all lab members are aware of hazards. Make sure that anyone who is about to enter the magnet room has been filled out consent and screening forms (subjects, lab members, visitors). Remove all metal, coins, credit cards etc. as soon as you enter the magnet area. Think! Train yourself to mini-screen yourself every time you approach the magnet room. Do not enter the magnet room with any tools (e.g., scissors). Use only magnetfriendly tools in the toolbox in the magnet room. Do the “Metal Macarena!” Specific Absorption Rate (SAR) • excess energy heats body tissues • if body heats faster than natural cooling, temperature rises • Specific Absorption Rate (SAR) = amount of heat absorbed by body • magnets have SAR limits to prevent overheating – limited to 1 degree rise in core body temperature – depends on body size, geometry, thermoregulation – depends on pulse sequences (e.g., larger flip angles = greater SAR) Other safety issues • fire safety – – – – always give subjects a panic button make sure that subject can be evacuated quickly if needed have an MR-compatible fire extinguisher available operator must know safety protocols • quenching – – – – rapid decrease in magnetic field strength helium boils off and can fill room (displacing oxygen) can occur spontaneously only voluntarily initiated in extreme situations • burns – do not loop any wires or cables – do not place electrodes on subjects’ skin Other safety issues • claustrophobia – subject screening • peripheral nerve stimulation – rapid switching of gradients can lead to generation of currents in the body that stimulate the nerves (e.g., twitching) – manufacturers limit rate of gradient switching to avoid problems • acoustic noise – – – – without ear protection, could cause hearing loss soundproofing earplugs headphones