# Presentation: 784673

## Choosing the Optimal Sequences and Strategies for Functional MRI

- Peter A. Bandettini, Ph.D
- Unit on Functional Imaging Methods
- Laboratory of Brain and Cognition
- National Institute of Mental Health

## Variables to Optimize 

**Information Content**
**Sensitivity**
**Speed**
**Resolution**
**Image quality**

## Variables to Optimize 

**Information Content**
**Sensitivity**
**Speed**
**Resolution**
**Image quality**

## Information Content

**Blood Volume**
**Blood Oxygenation**
**Blood Perfusion**
**Hemodynamic Specificity**
**Mapping of CMRO****2**

## Contrast agent injection and time series collection of T2* or T2 - weighted images

**Blood Volume**

## Blood Volume

## Susceptibility Contrast

**Susceptibility Contrast**

## Blood Oxygenation

**Blood Oxygenation**

## BOLD Contrast in the Detection of Neuronal Activity

**BOLD Contrast in the Detection of Neuronal Activity**

**Cerebral Tissue Activation**

**Local Vasodilation**

**Increase in Cerebral Blood**
**Flow and Volume**

**Oxygen Delivery Exceeds**
**Metabolic Need**

**Increase in Capillary and Venous Blood Oxygenation**

**Decrease in Deoxy-hemoglobin**

***Deoxy-hemoglobin: paramagnetic***
***Oxy-hemoglobin: ******	******diamagnetic***

**Decrease in susceptibility-related**
**intravoxel dephasing**

**Increase in T2 and T2***

**Local Signal Increase in T2 and T2* - weighted sequences**

## The BOLD Signal

- _B_lood _O_xygenation _L_evel _D_ependent (BOLD)  signal changes

*task*

*task*

## Slide 11

## Blood Perfusion

**EPISTAR**

** **

** **

** **

** **

**FAIR**

** **

** **

** **

**. . .**

**. . .**

**Perfusion**
**Time Series**

**-**

**-**

**-**

**-**

## FAIR

**FAIR**

**EPISTAR**

## BOLD

**BOLD**

**Perfusion**
*Rest**	**	**Activation*

## Anatomy

**Anatomy**

**BOLD**

**Perfusion**

## +				-

**BOLD**
**Perfusion**

**+****	****	****	****	****-**

**• ****unique information**
**• ****baseline information**
**• ****multislice trivial**

**• ****highest C / N**
**• ****easy to implement**
**• ****multislice trivial**
**• ****non invasive**
**• ****highest temp. res.**

**• ****unique information**
**• ****control over ves. size**
**• ****baseline information**
**• ****non invasive**

**• ****invasive**
**• ****low C / N for func.**

**• ****complicated signal**
**• ****no baseline info.**

**• ****multislice non trivial**
**• ****lower temp. res.**
**• ****low C / N**

## Hemodynamic Specificity

**Venous inflow**
**(Perf. No VN)**

**Arterial inflow**
**(BOLD TR < 500 ms)**

**Hemodynamic Specificity**

## Activation: 		Flow
				CMRO2
				Blood Oxygenation

CO2 stress: 		Flow
				CMRO2
				Blood Oxygenation

**	****	****	****	****CMRO****2**
**	****	****	****	****Blood Oxygenation**
**	****	****	****	**** **
**CO****2**** stress:**** ****	****	****Flow**
**	****	****	****	****CMRO****2**
**	****	****	****	****Blood Oxygenation**

**Mapping of CMRO****2**

## CMRO2-related BOLD signal deficit:

- CMRO2-related BOLD signal deficit:

- N=12

**CBF**

**BOLD**

**Simultaneous Perfusion and BOLD imaging**
**during graded visual activation and hypercapnia**

***Hoge, et al.***

**Notes:**
here we see the resultant perfusion and BOLD responses;
on the left, we see that the perfusion increases evoked by the two stimulus types are well matched...
while on the right we see that the BOLD signals are significantly different.
what is happening here is that increased dHb production associated with accelerated aerobic metabolism during brain activation is attenuating the visually evoked BOLD signal.

## CBF-CMRO2 coupling

**Characterizing Activation-induced CMRO****2**** changes**
**using calibration with hypercapnia**

***Hoge, et al.***

**Notes:**
this scatter plot shows the visually evoked responses in green, with the hypercapnically evoked baseline CMRO2 data in red.
iso-CMRO2 contours are also shown...
while it is clear that the BOLD-perfusion relationships for vasodilatory stimulation and neuronal activation are significantly different, the BOLD-perfusion relationship for different visual stimuli was quite consistent - even for stimuli known to activate tissues with different enzymatic makeup.
in addition to my measurements, most literature results for many different types of task and tissue type also fall within the area delineated by the dashed line here...  
2% BOLD increases and 50% perfusion increases are pretty standard for most paradigms, which usually attempt to stimulate to maximal levels.

## Computed CMRO2 Changes

- Computed CMRO2 Changes

**Subject 1**

**Subject 2**

**%**

**%**

**40**

**0**

**10**

**20**

**30**

**-10**

**-20**

**-30**

**-40**

***Hoge, et al.***

## Variables to Optimize

**Information Content**
**Sensitivity**
**Speed**
**Resolution**
**Image quality**

## Sensitivity

**Optimizing fMRI Contrast**
**Maximizing Signal**
**Reducing Physiologic Fluctuations**
**Minimizing Temporal Artifacts**

## Optimizing fMRI Contrast

**Increase field strength**
**Adjust pulse sequence timing (TE ≈ T2*)**
**Adjust voxel volume (≈ activation volume)**

## Slide 25

## Gradient - Echo

**Gradient - Echo**

**Asymmetric**
**Spin - Echo**

## Gradient - Echo

**Gradient - Echo**

**Asymmetric**
**Spin - Echo**

## Maximizing Signal

- Higher Bo Field
- Radio frequency Coils
- Choice of repetition time (TR)
- Voxel volume

## Physiologic Fluctuations

**Cardiac****	****	****0.6 to 1.2 Hz **
**Respiratory ****	****0.1 to 0.2 Hz**
**Low Frequency****	****0.0 to 0.1 Hz**

## 0.25 Hz Breathing at 1.5T

**Image**

**Respiration map**

**0                      0.25                      0.5  ****Hz**

**0.25 Hz Breathing at 1.5T**

**3ms**

**26ms**

**49ms**

**3ms**

## 0.68 Hz Cardiac rate at 3T

**3ms**

**26ms**

**49ms**

**0         0.68 (aliased)                 0.5**
**Hz**

**0.68 Hz Cardiac rate at 3T**

**Power Spectra**

**Image**

**Cardiac map**

## Temporal vs. Spatial SNR- 3T

**26ms**

**49ms**

**SPIRAL**

**EPI**

**27ms**

**50ms**

**26ms**

**49ms**

**27ms**

**50ms**

## Reducing Physiologic Fluctuations

- Filtering
- Pulse sequence
- single vs. multishot
- strategies for multishot
- Gating with correction for variable TR

## Temporal Artifacts

- System instabilities
- Motion
- Drift
- Stimulus correlated
- Stimulus uncorrelated

## Minimizing

**Temporal**
**Artifacts**

**Recognize?**
**Edge effects**
**Shorter signal change latencies**
**Unusually high signal changes**
**External measuring devices**
**Correct?**
**Image registration algorithms**
**Orthogonalize to motion-related function *****(cardiac, respiration, movement)***
**Navigator echo for k-space alignment ****	****	*****(for multishot techniques)***
**Re-do scan**
**Bypass?**
**Paradigm timing strategies..**
**Gating (with T1-correction)**
**Suppress?**
**Flatten image contrast**
**Physical restraint**
**Averaging, smoothing**

## Slide 36

## Slide 37

## 2

- 3

- 4

- 5

- 6

- 7

- 8

- 9

- 10

- 11

- 12

- 13

- Overt Word Production

## Tongue Movement

- Jaw Clenching

## Variables to Optimize

**Information Content**
**Sensitivity**
**Speed**
**Resolution**
**Image quality**

## Rapid imaging techniques:
Single shot imaging
TR vs. Brain coverage: 
min TR = (time/slice) x number of slices in volume 
Hemodynamic Issues
Paradigm timing
Event related fMRI
Timing modulation

- Single shot imaging
- TR vs. Brain coverage:
- min TR = (time/slice) x number of slices in volume
- Hemodynamic Issues
- Paradigm timing
- Event related fMRI
- Timing modulation

**Speed**

## Single Shot Imaging

**T2* decay**

**EPI Readout Window**

**≈ ****20 to 40 ms**

## Slide 43

## Time (sec)

**Time (sec)**

## Slide 46

## Compute nonlinearity (for each voxel)

-   Amplitude of Response

-   Area under response / Stimulus Duration

*Fit ideal (linear) to response*

*Output Area / Input Area*

## Nonlinearity

- Stimulus Duration

- Stimulus Duration

*Magnitude*

*Area*

- Output / input

- Output / input

*linear*

- Visual

- Motor

## Results – visual task

- Nonlinearity

- Magnitude

- Latency

## Results – motor task

- Nonlinearity

- Magnitude

- Latency

## Slide 51

## Slide 52

## Latency

**Latency**

**Magnitude**

**+ 2 sec**

**- 2 sec**

## Temporal Normalization

**Relative Timing**

**Temporal Normalization**

## Regions of Interest Used for Hemi-Field Experiment

- <date/time>

- Regions of Interest Used for Hemi-Field Experiment

**Right Hemisphere**

**Left Hemisphere**

## Slide 56

## Hemi-field with 500 msec asynchrony

- <date/time>

**Percent**

**MR**

**Signal**

**Strength**

**Time (seconds)**

**Average of 6 runs     Standard Deviations Shown**

## Percent

- <date/time>

**Percent**

**MR**

**Signal**

**Strength**

**Time (seconds)**

**Average of 6 runs     Smoothed Data**

## =

**+ 2.5 s**

**- 2.5 s**

**0 s**

**500 ms**

**500 ms**

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

**Left Hemifield**

**-**

## =

**+ 2.5 s**

**- 2.5 s**

**0 s**

**250 ms**

**250 ms**

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

**Left Hemifield**

**-**

## Variables to Optimize

**Information Content**
**Sensitivity**
**Acquisition Speed**
**Resolution**
**Image quality**

## Multishot Imaging

**T2* decay**

**EPI Window 2**

## Partial k-space imaging

## Slide 64

## Slide 65

## Multi Shot EPI

**Excitations****	****1****	****	****2****	****	****4****	****	****8****	**
**Matrix Size****	****64 x 64****	****	****128 x 128****	****256 x 128 ****	****256 x 256**

**Multi Shot EPI**

## Slide 67

## Slide 68

## ODC Maps using fMRI

**calcarine**

**1 cm**

- 1Malonek D, Grinvald A. *Science* 272, 551-4 (1996).
- 3Horton JC, Hocking DR. *J Neurosci* 16, 7228-39 (1996).
- 4Horton JC, et al. *Arch Ophthalmol* 108, 1025-31 (1990).

-  Identical in size, orientation, and appearance to those obtained by optical imaging1 and histology3,4.

## fMRI Timecourse within an ODC

- time (s)

- % change in MR signal

- corresponding eye
- stimulation

- fellow eye
- stimulation

- stimulus duration

- For a 4 second stimulus, the hyperoxic response does not saturate (i.e., does not reach a plateau).
- The ratio of the peak magnitudes of the fMRI responses is nearly 3:1.

## Experiment 2: Stimulus Duration

- The saturation of the hyperoxic response does not permit reliable mapping of ODCs.
- ODC maps obtained using the hyperoxic phase of the BOLD fMRI signal *are*  reliable when stimulus duration is 4 seconds or less.

## Variables to Optimize

**Information Content**
**Sensitivity**
**Speed**
**Resolution**
**Image quality**

## Image Quality

- Minimizing warping
- Shimming
- Reduced readout window duration
- Minimizing dropout
- Shimming
- Reduced TE
- Adjust slice orientation
- Increase resolution

## Neuronal Activation Input Strategies

**1. Block Design**
**2. Frequency Encoding**
**3. Phase Encoding**
**4. Event Related**
**5. Orthogonal Block Design**
**6. Free behavior Design.**

## M.A. Burock et al. NeuroReport, 9, 3735-9 (1998)

## Definitions

- ISI

- min. SD

- ISI

- ISI

- SD

- Blocked
- Trial

- Event-Related
- Constant ISI

- Event-Related
- Variable ISI

## Detection – constant ISI

- 0

- 10

- 20

- 30

- 40

- ISI

- Detectability

- 0

- 10

- 20

- 30

- 40

- ISI

- Contrast

- ISI

*Optimal detection when there is no overlap*

## Detection vs. ISI – different SD

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- ISI (s)

- Detectability

- SD = 1000 ms.

- SD = 250 ms.

- SD = 4000 s.

- ISI

- SD

*Optimal detection when there is no overlap*

## Detection: Contrast

- Stimulus

- Response

- task

- control

- task

- control

## Detection vs. % “on” – variable ISI

- 0

- 0.2

- 0.4

- 0.6

- 0.8

- 1

- Fraction in task state

- Detectability

## Detection vs. Average ISI

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- average ISI (s)

- Detectability

- 2

- min. SD = 1 s

- 2

- variable ISI

- constant ISI

## Detection vs. average ISI

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- average ISI (s)

- Detectability

- SD = 1000 ms.

- SD = 250 ms.

- SD = 4000 s.

## Detection – 50% “on”

- minimum Stimulus Duration

- stimulus timing

- stimulus timing

## Estimation accuracy vs. average ISI

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- average ISI (s)

- Estimation Accuracy

- SD = 1 s

- 2

## Estimation accuracy vs. average ISI

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- 0

- 5

- 10

- 15

- 20

- average ISI (sec)

- Estimation Accuracy

- SD = 4000 ms.

- SD = 1000 ms.

- SD = 250 ms.

## Estimation accuracy – 50% “on”

- 0

- 5

- 10

- 15

- 20

- minimum Stimulus Duration (s)

- Estimation Accuracy

## Detection and Estimation

- 0

- 5

- 10

- 15

- 20

- minimum Stimulus Duration (s)

- Detectability

- Estimation accuracy

## Acknowledgements

**Robert Savoy**
**Ravi Menon**
**Eric Wong**
**Rick Hoge**
**&...**

## Functional Imaging Methods / 3T Group	

**Sean Marrett**
**Jerzy Bodurka**
**Post Docs:**
**Rasmus Birn**
**Patrick Bellgowan**
**Ziad Saad**
**Clinical Fellow:**
**James Patterson**
**Graduate Student:**
**Natalia Petridou**
**Summer Students:**
**Hannah Chang**
**Courtney Kemps**

**July 7, 2000**

**Functional Imaging Methods / 3T Group**