# Presentation: 656696

## Peter A. Bandettini, Ph.D

Unit on Functional Imaging Methods
&
3T Neuroimaging Core Facility

Laboratory of Brain and Cognition
National Institute of Mental Health

- Unit on Functional Imaging Methods
- &
- 3T Neuroimaging Core Facility
- Laboratory of Brain and Cognition
- National Institute of Mental Health

**The Future of Functional MRI**

## Slide 2

## Methodology

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**Methodology**

- Hemoglobin

- Blood T2

- IVIM

- Baseline Volume

**Interpretation**

**Applications**

- Volume-V1

- BOLD

- Correlation Analysis

- Linear Regression

- Event-related

- BOLD -V1, M1, A1

- TE dep

- Veins

- IV vs EV

- BOLD models

- ASL

- Deconvolution

- Phase Mapping

- V1, V2..mapping

- Language

- Memory

- Presurgical

- Attention

- PSF of BOLD

- Pre-undershoot

- Ocular Dominance

- Mental Chronometry

- Electrophys. correlation

- 1.5T,3T, 4T

- 7T

- SE vs. GE

- Performance prediction

- Emotion

- Real time fMRI

- Balloon Model

- Post-undershoot

- Inflow

- PET correlation

- CO2 effect

-  CO2 Calibration

- Drug effects

- Optical Im. Correlation

- Imagery

- Clinical Populations

- Plasticity

- Complex motor

- Motor learning

- Venography

- Face recognition

- Children

- Simultaneous ASL and BOLD

- Surface Mapping

- Linearity

- Mg+

- Dynamic IV volume

- Bo dep.

- Diff. tensor

- Volume - Stroke

- Z-shim

- Free-behavior Designs

- Extended Stim.

- Local Human Head Gradient Coils

- NIRS Correlation

- SENSE

- Baseline Susceptibility

- Metab. Correlation

- Fluctuations

- Priming/Learning

- Resolution Dep.

- Tumor vasc.

**Technology**

- EPI on Clin. Syst.

- EPI

- Quant. ASL

- Multi-shot fMRI

- Parametric Design

- Current Imaging?

- Multi-Modal Mapping

- Nav. pulses

- Motion Correction

- MRI

- Spiral EPI

- ASL vs. BOLD

- >8 channels

- Multi-variate Mapping

- ICA

- Fuzzy Clustering

- Mixed ER and Blocked

- Linearity mapping

## Methodology

**Methodology**

**Interpretation**

**Applications**

**Technology**

**Physicist**
**Engineer**
**Computer Scientist**
**Statistician**
**Clinician**
**Basic Neuroscientist**
**Cog Neuroscientist**
**Physiologist**

## Where fMRI Will Improve:

**Sensitivity**
**Spatial Resolution**
**Temporal Resolution**
**Image Quality**
**Interpretation**
**Experimental **
**	****Design/Execution/Analysis**

## Why do we need Sensitivity?

**More signal exists **
**More information in the fluctuations**
**Allows shorter scan times**
**Allows more subtle comparisons**
**Allows higher resolution**

## Continuously Growing

- Activation Area

- Inflection Point

- CC Histogram

- Z. S. Saad, K. M. Ropella, E. A. DeYoe, P. A. Bandettini, The spatial extent of the BOLD response.  *NeuroImage, *(*in press).*

**Notes:**
(perhaps show only six and keep going up till 22).
This is a plot of the number of activated voxels detected versus the number of averaged scans.
This data is from the 3T.
The red data represents positive responses and the green data represents negative responses. 
Different dots at any one number of average scans represents the estimates from the different permutations.
The curves represent linear fits to the average number of activated voxels versus Navg.
Note the dramatic increase in the number of activated voxels with Navg. This function fits a linear curve with a correlation of ~92-97%. 
Note also the very large scatter of the number of activated voxels for voxels in a single rep. (perhaps put the subject performance and the number of voxels versus repno here ...)

## Williams, D. S., Detre, J. A., Leigh, J. S. & Koretsky, A. S. (1992) “Magnetic resonance imaging of perfusion using 

- Williams, D. S., Detre, J. A., Leigh, J. S. & Koretsky, A. S. (1992) “Magnetic resonance imaging of perfusion using
- spin-inversion of arterial water.” Proc. Natl. Acad. Sci. USA 89, 212-216.
- Edelman, R., Siewert, B. & Darby, D. (1994) “Qualitative mapping of cerebral blood flow and functional localization
- with echo planar MR imaging ans signal targeting with alternating radiofrequency (EPISTAR).” Radiology
**192**, 1-8.
- Kim, S.-G. (1995) “Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion
- recovery (FAIR) technique: application to functional mapping.” Magn. Reson. Med. **34**, 293-301.
- Kwong, K. K. et al. (1995) “MR perfusion studies with T1-weighted echo planar imaging.”Magn. Reson. Med. **34**,
- 878-887.

## How to Increase Sensitivity?

**Higher field strength**
**More and Smaller RF coils**
**Pulse sequences?**

## Quadrature Head Coil

**Quadrature Head Coil**

**8 Channel Array**

**128 x 96**

**128 x 96**

**64 x 48**

**SNR**

**TSNR**

## Slide 11

## Why to we need higher 

**spatial resolution?**

**Greater delineation of function**
**Possible gain in contrast to noise**
**Reduction of signal dropout**
**Better registration with high res. Anatomy**
**With Regard to functional resolution: calibration**

## Ocular Dominance Column Mapping using fMRI

**calcarine**

**Menon, R. S., S. Ogawa, et al. (1997). “Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging.” **_**J Neurophysiol**_** 77(5): 2780-7.**

**R. D. Frostig et. al, PNAS 87: 6082-6086, (1990).**

**Ocular Dominance Column Mapping using fMRI**

**Optical Imaging**

## How to Increase Resolution?

**Multi-shot Imaging (with navigators)**
**Partial k-space**
**Parallel imaging (SENSE, SMASH, etc..)**

## Single Shot EPI

**T2* decay**

**EPI Readout Window**

**≈ ****20 to 40 ms**

## Multishot Imaging

**T2* decay**

**EPI Window 2**

## Partial k-space imaging

## ≈ 5 to 30 ms

**≈ ****5 to 30 ms**

**Pruessmann, et al. **

**SENSE Imaging**

## Why do we need higher 

**temporal resolution?**

**More slices per volume**
**Better delineation of hemodynamic response**
**Possibly better delineation of cascaded neuronal activity**

## How to Increase 

**temporal resolution?**

**Asynchronous task and TR timing**
**Reduce readout window width**
**Increased averaging**
**Focus on modulation of task timing**
**Calibration?**

## 0

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- 100

- 200

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- Number of runs

- 8 sec on/off

- 16 sec on/off

- Smallest latency
- Variation Detectable
- (ms) (p < 0.001)

- t

- 1 run:

- -1000

- -500

- 500

- 1000

- Number

- delay estimate (ms)

- delay = 107ms

**11**

- 1% Noise
- 4% BOLD
- 256 time pts /run
- 1 second TR

## Optimal Detection of Hemodynamic Latency

**Optimal Detection of Hemodynamic Latency**

## ?

**Hemodynamics**

**?**

**?**

**?**

**Measured Signal**

**Noise**

## Latency

**Latency**

**Magnitude**

**+ 2 sec**

**- 2 sec**

## Hemi-Field Experiment

**Right Hemisphere**

**Left Hemisphere**

## =

**+ 2.5 s**

**- 2.5 s**

**0 s**

**500 ms**

**500 ms**

**Right**** ****Hemifield**

**Left Hemifield**

**-**

## Hemodynamic Response Modulation

**Bottleneck**
**In Processing**
**(upstream)**

**Delayed**
**Processing**
**(downstream)**

**Hemodynamic Response Modulation**

## P.S.F. Bellgowan, Z. S. Saad, P. A. Bandettini, Understanding neural system dynamics through task modulation and measurement of BOLD amplitude, latency, and width. Proc. Nat'l. Acad. Sci. USA  (in press). 

*Our first attempt to apply this strategy..*

## Use of Task Timing Modulation to Extract Processing Streams  

- Use of Task Timing Modulation to Extract Processing Streams

- Stimuli – Six-letter English words and pronounceable non-words.
- 	   Each word or non-word was rotated either 0, 60,or 120 degrees
- Task – Lexical Decision (word / non-word).
- Dependent Measures – Percent Correct and Reaction Time.

- Hypotheses :
- 	**1) Stimulus rotation of 120 degrees will result in:**
- 		a) Longer Reaction Times
- 		b) Stimulus rotation demands a change in perceptual
- 		perspective prior to linguistic processing, resulting in a
- 		delayed IRF onset in areas involved in Lexical and Pre-Lexical
- 		processing.
- 	 2**) Lexical discrimination will result in :**
- 		a) Longer Reaction Times for non-words due to
- 		increased Pre-Lexical processing demands.
- 		b) Wider IRF in Inferior Frontal cortex for non-words
- 		c) Delayed IRF onset in Left Middle Frontal Cortex

## Slide 30

## Estimation of Delay, Width & Amplitude

**time (s)**

**Conv.**

**Adjust ********** to improve fit ****(Nelder-Mead simplex method)**

**5**

**10**

**15**

**0**

**0**

**20**

**Magnitude**

**Delay**

**Width**

- Warm colors are areas where Words > Non-words.  Cool colors (blues) are areas. Where Non-words > words. The Left hemisphere is toward the left margin. The green arrows highlight the inferior frontal gyrus.

## Slide 33

## Regions of Interest

- Word vs. Non-word

- 0o, 60o, 120o Rotation

- Inferior Frontal Gyrus

- Precentral Gyrus

- Middle Temporal Gyrus

## What is needed in image quality?

**Reduction of warping**
**Reduction of signal dropout**
**Reduction of ghosting, etc. artifacts**

## Slide 36

## Improving Image Quality

**Reduction of warping**
**Shorter readout window length (SENSE, etc..)**
**Shimming**
**Reduction of signal dropout**
**Shimming**
**Pulse sequence correction (Z-shim, etc..)**
**Smaller voxel volumes**
**Reduction of ghosting, etc. artifacts**
**Better phase correction**
**Better coil performance**

## Interpretation

**More direct neuronal information**
**More quantitative physiologic information**

##  Neuronal Activity

- Number of Neurons

- Spiking Rate

- Local Field Potential

- Metabolism

- Hemodynamics

- Blood
- Volume

- Flow Velocity

- Aerobic Metabolism

- Anaerobic Metabolism

- BOLD Contrast

**-**

**-**

- Spiking Coherence

- Deoxy-Hb

- Oxygenated
- Blood

- Deoxygenated
- Blood

**+**

- MRI Pulse
- Sequence

- Perfusion

- Perfusion Contrast

- Inflow Contrast

## ?

**Hemodynamics**

**?**

**?**

**?**

**Measured Signal**

**Noise**

## Different stimulus “ON” periods

- measured

- linear

- Signal

- 0.25 s

- 0.5 s

- 1 s

- 2 s

- 20 s

- Stimulus
- timing

- BOLD
- Response

*Brief stimuli produce larger responses than expected*

**Dynamic Nonlinearity Assessment**

**R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” *****NeuroImage*****, 14: 817-826.**

## Spatial Heterogeneity of BOLD Nonlinearity

**R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” *****NeuroImage*****, 14: 817-826.**

**Spatial Heterogeneity of BOLD Nonlinearity**

## Sources of this Nonlinearity

- Neuronal
- Hemodynamic
- Oxygen extraction
- Blood volume dynamics

- Volume

- Flow In

- Flow Out

- Oxygen Extraction

## BOLD Correlation with Neuronal Activity

**Logothetis et al. (2001) “****Neurophysiological investigation of the basis of the fMRI signal” ****Nature, 412, 150-157.**

**P. A. Bandettini and L. G. Ungerleider, (2001) “From neuron to BOLD: new connections.” Nature Neuroscience, 4:  864-866.**

## Computed CMRO2 Changes

**Subject 1**

**Subject 2**

**%**

**%**

**40**

**0**

**10**

**20**

**30**

**-10**

**-20**

**-30**

**-40**

- Computed CMRO2 Changes

## CBF

**CBF**

**OEF**

**CMRO****2**

## Neuronal Current Imaging

- These bio-currents induce **spatially distributed and transient** magnetic flux density changes and magnetic field gradients.
- In the context of MRI, these currents therefore alter **the magnetic phase** of surrounding water protons.

## J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes, Magn. Reson. Med. 47: 1052-1058, (2002). 

**J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes, Magn. Reson. Med. ****47: 1052-1058, (2002****). **

## results

**results**

- A: activity, on-off frequency (appx. 7 sec)
- B: activity
- C: scanner noise (cooling-pump)

- _Active_ state: black line, _Inactive_ state: red line

- A

- B

- C

- A

- B

- C

*1: *_*culture*_

*2: *_*CSF*_

- FSE image

**Hz**

**Hz**

**CSF**

**detection of neuronal currents in vitro**

**Culture**

**Notes:**
Note: each culture has a different on-off frequency (some of the cultures we had were epileptic, like this one, and I assume they had different activity patterns than non-epileptic ones). This spectrum was calculated with a sliding window fft of 150sec.

## Power spectra

- 0.5 Hz

- 0.5 Hz

**Eyes closed**

**Eyes open**

- Phase v=0.12Hz

- Closed

- Open

## Experimental 

**Design, Execution, and Analysis**

## Neuronal Activation Input Strategies

**Block Design**
**2. Parametric Design**
**3. Frequency Encoding**
**4. Phase Encoding**
**5. Event Related**
**6. Orthogonal Design**
**7.**** ****Free Behavior Design**

## Detectability – constant ISI

- Average ISI (s)

- Detectability

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- 40

- SD – stimulus duration

- ISI – inter-stimulus interval

## Detectability vs. Average ISI

- 0

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- 40

- average ISI (s)

- Detectability

- SD = 1000 ms.

- SD = 250 ms.

- SD = 4000 s.

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

## Estimation accuracy vs. average ISI

- 0

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- 40

- 0

- 5

- 10

- 15

- 20

- average ISI (sec)

- Estimation Accuracy

- SD = 4000 ms.

- SD = 1000 ms.

- SD = 250 ms.

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

## Slide 56

## Free Behavior Design

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

## 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 fMRI study. *NeuroImage*,  **17**: 1787-1806, (2002).

## OHBM 2002

**OHBM 2002**

## Methodology

**Methodology**

**Interpretation**

**Applications**

**Technology**

## FIM Unit & FMRI Core Facility 	

**Peter Bandettini**
**Staff Scientists:**
**Sean Marrett**
**Jerzy Bodurka**
**Frank Ye**
**Wen-Ming Luh**
**Computer Specialist:**
**Adam Thomas**
**Post Docs:**
**Rasmus Birn**
**Hauke Heekeren**
**David Knight**
**Patrick Bellgowan**
**Ziad Saad**

**FIM Unit & FMRI Core Facility **

**Graduate Student:**
**Natalia Petridou**
**Post-Back. IRTA Students:**
**Elisa Kapler**
**August Tuan**
**Dan Kelley**
**Visiting Fellows:**
**Sergio Casciaro**
**Marta Maieron**
**Guosheng Ding**
**Clinical Fellow:**
**James Patterson**
**Psychologist:**
**Julie Frost**

**Summer Students:**
**Hannah Chang**
**Courtney Kemps**
**Douglass Ruff**
**Carla Wettig**
**Kang-Xing Jin**** **
**Program Assistant:**
**Kay Kuhns**
**Scanning Technologists:**
**Karen Bove-Bettis**
**Paula Rowser**