Latest Developments in f MRI Peter A Bandettini

Latest Developments in f. MRI Peter A. Bandettini, Ph. D Unit on Functional Imaging Methods & 3 T Neuroimaging Core Facility Laboratory of Brain and Cognition National Institute of Mental Health

Technology Methodology Interpretation Applications

Technology Methodology Engineers Statisticians Physicists Mathematicians Neuroscientists Physiologists Interpretation Clinicians Applications

Technology 1. 5 T, 3 T, 4 T EPI Diff. tensor EPI on Clin. Syst. Local Human Head Gradient Coils BOLD Dynamic IV volume IVIM Deconvolution Event-related Fuzzy Clustering BOLD models PET correlation IV vs EV ASL vs. BOLD Bo dep. Pre-undershoot PSF of BOLD TE dep Resolution Dep. Extended Stim. Post-undershoot Metab. Correlation Linearity SE vs. GE CO 2 effect Optical Im. Correlation Fluctuations NIRS Correlation Balloon Model Electrophys. correlation Inflow Veins Interpretation Blood T 2 Hemoglobin Complex motor Language Applications BOLD -V 1, M 1, A 1 Volume - Stroke D Volume-V 1 88 Current Imaging? CO 2 Calibration Motion Correction Parametric Design Multi-Modal Mapping Surface Mapping Free-behavior Designs ICA Phase Mapping Mental Chronometry Multi-variate Mapping Linear Regression Baseline Volume 82 Baseline Susceptibility Correlation Analysis Methodology 36 Z-shim Simultaneous ASL and BOLD Multi-shot f. MRI >8 channels SENSE Quant. ASL Spiral EPI ASL 7 T Venography Real time f. MRI Nav. pulses MRI Mg+ 89 90 91 92 Tumor vasc. Presurgical Attention Ocular Dominance Priming/Learning Plasticity 94 Emotion Motor learning Children V 1, V 2. . mapping 93 Memory Imagery 95 96 Face recognition 97 98 Drug effects Clinical Populations Performance prediction 99 00 01 02

Alternating Left and Right Finger Tapping ~ 1992

The use of f. MRI for the Investigation of Brain Function and Physiology • Where? • When? • How much? • How to do it well? • Is there more?

A Primary Challenge for Observing Brain Activation with f. MRI: . . . to make progressively more precise inferences without making too many assumptions about non-neuronal physiologic factors.

Neuronal Activation ? Measured Signal Hemodynamics ? ? Noise

Latest Developments… 1. Temporal Resolution 2. Spatial Resolution 3. Sensitivity and Noise 4. Information Content 5. Implementation

Single Shot EPI T 2* decay EPI Readout Window ≈ 20 to 40 ms

P. A. Bandettini, Functional MRI temporal resolution in "Functional MRI" (C. Moonen, and P. Bandettini. , Eds. ), p. 205 -220, Springer - Verlag, . 1999.

Latency + 2 sec - 2 sec Magnitude P. A. Bandettini, The temporal resolution of Functional MRI in "Functional MRI" (C. Moonen, and P. Bandettini. , Eds. ), p. 205 -220, Springer - Verlag, . 1999.

Venogram (3 Tesla)

Hemi-Field Experiment Right Hemisphere Left Hemisphere 9. 0 seconds 15 seconds 500 msec 10 20 Time (seconds) 30

0 500 ms 10 500 ms 20 30 Right Hemifield Left Hemifield + 2. 5 s 0 s - 2. 5 s - =

Hemodynamic Response Modulation Bottleneck In Processing (upstream) Delayed Processing (downstream)

11026– 11031 PNAS September 26, 2000 vol. 97 no. 20

Latest Developments… 1. Temporal Resolution 2. Spatial Resolution 3. Sensitivity and Noise 4. Information Content 5. Implementation

Single Shot Imaging T 2* decay EPI Readout Window ≈ 20 to 40 ms

Partial k-space imaging T 2* decay EPI Window

Partial k-space imaging Jesmanowicz, P. A. Bandettini, J. S. Hyde, (1998) “Single shot half k-space high resolution EPI for f. MRI at 3 T. ” Magn. Reson. Med. 40, 754 -762.

Multishot Imaging T 2* decay EPI Window 1 T 2* decay EPI Window 2

Multi Shot EPI Excitations Matrix Size 1 64 x 64 2 128 x 128 4 256 x 128 8 256 x 256

BOLD Perfusion Rest Activation P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, in "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed. ), p. 345 -371, W. B. Saunders Co. , 1997.

Anatomy BOLD Perfusion P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, in "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed. ), p. 345 -371, W. B. Saunders Co. , 1997.

Arterial inflow (BOLD TR < 500 ms) Venous inflow (for ASL, w/ no VN) Pulse Sequence Sensitivity Spatial Heterogeneity

ODC Maps using f. MRI Menon, et al 1 cm calcarine • Identical in size, orientation, and appearance to those obtained by optical imaging 1 and histology 3, 4. 1 Malonek D, Grinvald A. Science 272, 551 -4 (1996). 3 Horton JC, Hocking DR. J Neurosci 16, 7228 -39 (1996). 4 Horton JC, et al. Arch Ophthalmol 108, 1025 -31 (1990).

Latest Developments… 1. Temporal Resolution 2. Spatial Resolution 3. Sensitivity and Noise 4. Information Content 5. Implementation

Continuously Growing Activation Area CC Histogram Inflection Point Ziad Saad, et al

Temporal S/N vs. Image S/N PHANTOMS SUBJECTS 1400 1000 Temporal S/N 1200 1000 800 600 400 200 400 600 800 Image S/N 1000 1200 1400 0 200 400 600 800 Image S/N N. Petridou 1000

e s i o Signal to Noise Ratio N l a gn rm e h T / Si Signal / Physiologic Noise Optimal for f. MRI Resolution, Speed, Surface Coils, Field Strength, etc. .

Latest Developments… 1. Temporal Resolution 2. Spatial Resolution 3. Sensitivity and Noise 4. Information Content 5. Implementation

D Neuronal Activity Number of Neurons Local Field Potential Spiking Coherence Spiking Rate D Metabolism Aerobic Metabolism Anaerobic Metabolism D Hemodynamics Blood Volume Flow Velocity Perfusion D BOLD Contrast D Perfusion Contrast D Inflow Contrast - Deoxygenated Blood Oxygenated Blood MRI Pulse Sequence + D Deoxy-Hb

Motor Cortex S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex. ” J. Cereb. Blood Flow and Met. 16, 1250 -1254. Auditory Cortex J. R. Binder, et al, (1994). “Effects of stimulus rate on signal response during functional magnetic resonance imaging of auditory cortex. ” Cogn. Brain Res. 2, 31 -38

Logothetis et al. (2001) “Neurophysiological investigation of the basis of the f. MRI signal” Nature, 412, 150 -157 S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex. ” J. Cereb. Blood Flow and Met. 16, 1250 -1254.

BOLD Response Stimulus timing Signal Different stimulus “ON” periods 0. 25 s linear 0. 5 s measured 1 s 2 s 20 s time (s) Brief stimuli produce larger responses than expected

Results – visual task 8 f (SD) 6 4 2 0 1 -2 f (SD) 6 40 4 20 2 4 nonlinearity 6 3 4 5 0 10 20 30 40 8 60 02 2 Stimulus Duration 0 8 -2 1 2 3 4 5 Stimulus Duration

Results – visual task Nonlinearity Magnitude Latency

Sources of this Nonlinearity • Neuronal • Hemodynamic Oxygen Extraction – Oxygen extraction – Blood volume dynamics Flow In Flow Out D Volume

BOLD Correlation with Neuronal Activity Logothetis et al. (2001) “Neurophysiological investigation of the basis of the f. MRI signal” Nature, 412, 150 -157. P. A. Bandettini and L. G. Ungerleider, (2001) “From neuron to BOLD: new connections. ” Nature Neuroscience, 4: 864 -866.

CBF BOLD (% increase) 20 CBF (% increase) 15 10 5 0 -5 -10 0 200 400 600 800 1000 1200 1400 Time (seconds) 3 2 1 0 0 200 400 600 800 1000 1200 1400 Time (seconds) Simultaneous Perfusion and BOLD imaging during graded visual activation and hypercapnia N=12

Computed CMRO 2 Changes 40 30 20 10 0 -10 -20 -30 -40 Subject 1 Subject 2 %

CBF OEF CMRO 2

Latest Developments… 1. Temporal Resolution 2. Spatial Resolution 3. Sensitivity and Noise 4. Information Content 5. Implementation

Neuronal Activation Input Strategies 1. Block Design 2. 2. Parametric Design 3. Frequency Encoding 4. Phase Encoding 5. Event Related 6. Orthogonal Design 7. Free Behavior Design

First Event-related f. MRI Results Blamire, A. M. , et al. (1992). “Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging. ” Proc. Natl. Acad. Sci. USA 89: 11069 -11073.

Event Related Advantages • Task Randomization • Post acquisition, Performance-based, data binning • Natural presentation • Reduction of habituation effects • Overt responses • Reduction of scanner noise effects • More precise estimation of hemodynamic response

f. MRI during tasks that involve brief motion Blocked Design motion BOLD response task t Event-Related Design motion BOLD response task R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related f. MRI of tasks involving brief motion. Human Brain Mapping 7: 106 -114 (1999).

Overt Word Production 2 3 4 5 6 7 8 9 10 11 12 13 R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related f. MRI of tasks involving brief motion. Human Brain Mapping 7: 106 -114 (1999).

Speaking - Blocked Trial motion t Expected Response BOLD response t R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related f. MRI of tasks involving brief motion. Human Brain Mapping 7: 106 -114 (1999).

Speaking - ER-f. MRI avg Expected Response avg R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related f. MRI of tasks involving brief motion. Human Brain Mapping 7: 106 -114 (1999).

R. M. Birn, R. W. Cox, P. A. Bandettini, Detection versus estimation in Event. Related f. MRI: choosing the optimal stimulus timing. Neuro. Image 15: 262 -264, (2002).

Neuronal Activation Input Strategies 1. Block Design 2. 2. Parametric Design 3. Frequency Encoding 4. Phase Encoding 5. Event Related 6. Orthogonal Design 7. Free Behavior Design

Free Behavior Design Use a continuous measure as a reference function: • Task performance • Skin Conductance • Heart, respiration rate. . • Eye position • EEG

The Skin Conductance Response (SCR) Ventromedial PFC Orbitofrontal Cortex Hypothalamus Amygdala Sympathetic Nervous System Sweat Gland Resistance change across two electrodes induced by changes in sweating.

Brain activity correlated with SCR during “Rest” J. C. Patterson II, L. G. Ungerleider, and P. A Bandettini, Task - independent functional brain activity correlation with skin conductance changes: an f. MRI study. Neuro. Image (in press)

OHBM 2002

• Shimming • Acoustic Noise • Multishot Techniques • Increased Gradient Performance • Higher Field Strengths • Surface Coil Arrays • Calibration / Quantification • Embedded Functional Contrast • Noise / Fluctuations • Direct Neuronal Current Imaging • Clinical Populations • Neuronal, Vascular, and Metabolic Information

FIM Unit & FMRI Core Facility Director: Graduate Student: Summer Students: Peter Bandettini Natalia Petridou Hannah Chang Staff Scientists: Post-Back. IRTA Students: Courtney Kemps Sean Marrett Elisa Kapler Douglass Ruff Jerzy Bodurka August Tuan Carla Wettig Frank Ye Dan Kelley Kang-Xing Jin Wen-Ming Luh Visiting Fellows: Program Assistant: Computer Specialist: Sergio Casciaro Kay Kuhns Adam Thomas Marta Maieron Scanning Technologists: Post Docs: Guosheng Ding Karen Bove-Bettis Rasmus Birn Clinical Fellow: Paula Rowser Hauke Heekeren James Patterson David Knight Psychologist: Patrick Bellgowan Julie Frost Ziad Saad