An Introduction to Functional MRI Brain Imaging and

An Introduction to Functional MRI Brain Imaging and Analysis Center FMRI Graduate Course

Summary of the Course • Combines lectures and laboratory sessions – Laboratories will illustrate concepts from lectures • Grading basis – – Participation in course sessions (attendance, discussion) Completion of laboratory exercises One take-home test (mid-term) Practicum research project at end of semester • Course web page (www. biac. duke. edu/education) – BIAC Logins • Readings – Buxton, Introduction to f. MRI – Original papers (generally posted on the web page) – Full reading list to be posted over upcoming weeks

Outline for Today • • • Why use f. MRI to image brain function? Key concepts of f. MRI History of f. MRI Parts of a MR scanner MR safety • Laboratory: Scanner Visit (Dr. Jim Voyvodic) – Scanner hardware – Stimulus presentation and recording hardware – Demonstration of real-time f. MRI

What is f. MRI? • A technique for measuring changes in brain activity over time using principles of magnetic resonance. • Scanning procedures and restrictions are generally similar to clinical MR. • Most f. MRI studies use changes in BOLD contrast, although other measures exist.

Growth of f. MRI : Published Studies …

Why the Growth of f. MRI?

Why the Growth of f. MRI? • Powerful – Improved ability to understand cognition – Better spatial resolution than PET – Allows new forms of analysis • High benefit/risk ratio – Non-invasive (no contrast agents) – Repeated studies (multisession, longitudinal) • Accessible – Uses clinically prevalent equipment – No isotopes required – Little special training for personnel

New Cognitive Analyses • Sampling rate affects experimental design – PET: >30 s/data point ; f. MRI: 1 s/data point – Cognitive processes being measured must change more slowly than sampling rate • New forms of analyses – Event-related: sorting trials by accuracy, response time, type of condition – Rapid stimulus presentation • Allows creation of process models of activity – Difference in activation timing between regions is often on order of 100 -1000 ms

Cheng, Waggoner, & Tanaka (2001) Neuron Sakai, Rowe, & Passingham (2002) Nature Neuroscience

Image provided by Dr. James Voyvodic (Duke BIAC)

Key Concepts • • Contrast Spatial Resolution Temporal Resolution Functional Resolution

Anatomical Contrast Definition: The ability to distinguish between two (or more) different properties of tissue.

Blood Oxygenation Level Dependent (BOLD) Contrast From Mosley & Glover (1995)

Design Effects on Functional Contrast should really be considered as “contrast to noise”: how effectively can we decide whether a given brain region has property X or property Y?

Spatial Resolution: Voxels Voxel: A small rectangular prism that is the basic sampling unit of f. MRI. Typical functional voxel: (4 mm)3. Typical anatomical voxel: (1. 5 mm)3.

Spatial Resolution: Examples ~8 mm 2 ~4 mm 2 ~1. 5 mm 2 ~2 mm 2 ~1 mm 2

Temporal Resolution • Importance depends upon research question – Type I: Detection • Temporal resolution is only indirectly important if your study investigates whether or not a given brain region is active. – Type II: Estimation • Temporal resolution is extremely important when attempting to understand the properties of an active region. • Determining factors – Sampling rate, usually repetition time (TR) – Dependent variable, usually BOLD response • BOLD response is sluggish, taking 2 -3 seconds to rise above baseline and 4 -6 seconds to peak – Experimental design

From Jezzard et al. , 2001

Functional Resolution The ability of a measurement technique to identify the relation between underlying neuronal activity and a cognitive or behavioral phenomenon. Functional resolution is limited both by the intrinsic properties of our brain measure and by our ability to manipulate the experimental design to allow variation in the phenomenon of interest.

History of Magnetic Resonance Imaging

Timeline of MR Imaging 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1952 – Purcell and Bloch share Nobel prize in Physics. 1920 1930 1940 1950 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1960 1959 – Singer measures blood flow using NMR (in mice). 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1985 – Insurance reimbursements for MRI exams begin. 1973 – Lauterbur publishes method for generating images using NMR gradients. MRI scanners become clinically prevalent. NMR becomes MRI 1970 1980 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2 D-Fourier transform for MR. 1990 2000 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast.

Discovery of Nuclear Magnetic Resonance Absorption (1946) • Bloch and Purcell independently discovered how to measure nuclear moment in bulk matter (1946) – Determined relaxation times. • They showed that energy applied at a resonant frequency was absorbed by matter, and the reemission could be measured in detector coils Felix Bloch • They shared the 1952 Nobel Prize in Physics Edward Purcell

Timeline of MR Imaging 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1952 – Purcell and Bloch share Nobel prize in Physics. 1920 1930 1940 1950 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1960 1959 – Singer measures blood flow using NMR (in mice). 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1985 – Insurance reimbursements for MRI exams begin. 1973 – Lauterbur publishes method for generating images using NMR gradients. MRI scanners become clinically prevalent. NMR becomes MRI 1970 1980 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2 D-Fourier transform for MR. 1990 2000 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast.

Early Uses of NMR • Most early NMR was used for chemical analysis – No medical applications • 1971 – Damadian publishes and patents idea for using NMR to distinguish healthy and malignant tissues – “Tumor detection by nuclear magnetic resonance”, Science – Proposes using differences in relaxation times – No image formation method proposed • 1973 – Lauterbur describes projection method for creating NMR images – Mansfield (1973) independently describes similar approach

The First ZMR NMR Image Lauterbur, P. C. (1973). Image formation by induced local interaction: Examples employing nuclear magnetic resonance. Nature, 242, 190 -191.

Early Human MR Images (Damadian)

Mink 5 Image – Damadian (1977)

Timeline of MR Imaging 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1952 – Purcell and Bloch share Nobel prize in Physics. 1920 1930 1940 1950 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1960 1959 – Singer measures blood flow using NMR (in mice). 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1985 – Insurance reimbursements for MRI exams begin. 1973 – Lauterbur publishes method for generating images using NMR gradients. MRI scanners become clinically prevalent. NMR becomes MRI 1970 1980 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2 D-Fourier transform for MR. 1990 2000 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast.

Using MRI to Study Brain Function Visual Cortex: Kwong, et al. , 1994 Somatosensory Cortex: Hammeke, et al. , 1994

Parts of a MR Scanner BIAC 1. 5 T Scanner

MRI Safety Issue: The appropriate risk level for a research participant is much lower than for a clinical patient.

Hospital Nightmare Boy, 6, Killed in Freak MRI Accident July 31, 2001 — A 6 -year-old boy died after undergoing an MRI exam at a New Yorkarea hospital when the machine's powerful magnetic field jerked a metal oxygen tank across the room, crushing the child's head. … ABCNews. com

MR Incidents • Pacemaker malfunctions leading to death – At least 5 as of 1998 (Schenck, JMRI, 2001) – E. g. , in 2001 an elderly man died in Australia after being twice asked if he had a pacemaker • Blinding due to movements of metal in the eye – At least two incidents (1985, 1990) • Dislodgment of aneurysm clip (1992) • Projectile injuries (most common incident type) – Injuries (e. g. , cranial fractures) from oxygen canister (1991, 2001) – Scissors hit patient in head, causing wounds (1993) • Gun pulled out of policeman’s hand, hitting wall and firing – Rochester, NY (2000)

Issues in MR Safety • Magnetic Field Effects • Known acute risks – Projectiles, rapid field changes, RF heating, claustrophobia, acoustic noise, etc. • Potential risks – Current induction in tissue at high fields – Changes in the developing brain • Epidemiological studies of chronic risks – Extended exposure to magnetic fields • Difficulty in assessing subjective experience – In one study, 45% of subjects exposed to a 4 T scanner reported unusual sensations (Erhard et al. , 1995)

Possible Effects of Magnetic Fields • Physiological – Red blood cells (especially sickled) may alter shape in a magnetic field – Some photoreceptors may align with the field. • Sensory (generally reported in high-field) – – Nausea Vertigo Metallic taste Magnetophosphenes

Risks of MRI • • Projectile Effects: External Projectile Effects: Internal Radiofrequency Energy Gradient field changes Claustrophobia Acoustic Noise Quenching

Projectile Effects: External Chaljub (2001) Schenck (1996) “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 Chaljub (2001)

Radiofrequency Energy • Tissue Heating – Specific Absorption Rate (SAR; W/kg) • Pulse sequences are limited to cause less than a one-degree rise in core body temperature • Scanners can be operated at up to 4 W/kg (with large safety margin) for normal subjects, 1. 5 W/kg for compromised patients (infants, fetuses, cardiac) – Weight of subject critical for SAR calculations • Burns – Looped wires can act as RF antennas and focus energy in a small area • Most common problem: ECG leads • Necklaces, earrings, piercings, pulse oximeters, any other cabling

Projectile/Torsion Effects: Internal • Motion of implanted medical devices – Clips, shunts, valves, etc. • Motion or rotation of debris, shrapnel, filings – Primary risk: Metal fragments in eyes • Swelling/irritation of skin due to motion of iron oxides in tattoo and makeup pigments

Acoustic Noise • Potential problem with all scans – Short-term and long-term effects • Sound level of BIAC scanners – 1. 5 T: 93 -98 d. B (EPI) – 4. 0 T: 94 -98 d. B (EPI) • OSHA maximum exposure guidelines – 2 -4 hours per day at BIAC levels • Earplugs reduce these values by 14 -29 d. B, depending upon fit.

Gradient Field Changes • Peripheral nerve stimulation – May range from distracting to painful – Risk greatly increased by conductive loops • Arms clasped • Legs crossed • Theoretical risk of cardiac stimulation – No evidence for effects at gradient strengths used in MRI

Claustrophobia • Most common subject problem – About 10% of patients – About 1 -2% of BIAC subjects • Ameliorated with comfort measures – – Talking with subject Air flow through scanner Panic button Slow entry into scanner

Quenching • Definition: Rapid decrease in magnetic field strength due to loss of superconductivity – Only initiated voluntarily due to danger to participant’s life or health • Effects – Magnets heat up with loss of current – Cryogenic fluids (Helium) boil off and fill the scanner room • Displaces breathable air from room • Cooling of room, condensation reduces visibility – Physical damage to the scanner may occur – Safety personnel must be cognizant of room conditions

Scanner Visit • Anyone with implanted metal should see me before going to the scanner – Pacemaker, cochlear implant, shunt, clip, etc. – Dental work and piercings are fine • Please do not bring backpacks, books, etc. , – You can leave them here in the room, which we will lock • MR center is a working patient environment