# Presentation: 181168

## Latest Developments in fMRI

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

## The use of fMRI for the Investigation 

- The use of fMRI for the Investigation
- of Brain Function and Physiology

**Where?**
**When?**
**How much?**
**How to get the brain to do what we want it to **
**do in the context of an fMRI experiment?**
**(*****limitations*****: limited time and signal to noise, motion, acoustic noise)**
**How much more information can we obtain?**

## ?

**Neuronal**

**Activation**

**Hemodynamics**

**Measured**

**fMRI**

**Signal**

**?**

**?**

**Physiologic Factors**

## A Primary Challenge for Observing Brain Activation:

**...to make progressively more precise inferences without making **
**too many assumptions about non-neuronal physiologic factors.**

## Blood Volume
Contrast agent injection and time series collection of T2* or T2 - weighted images
BOLD
Time series collection of T2* or T2 - weighted images
Perfusion
T1 weighting
Arterial spin labeling	

**Blood Volume**
**Contrast agent injection and time series collection of T2* or T2 - weighted images**
**BOLD**
**Time series collection of T2* or T2 - weighted images**
**Perfusion**
**T1 weighting**
**Arterial spin labeling****	**

**Contrast in Functional MRI**

## Resting		   Active

**Resting****	****	****   ****Active**

## Slide 7

## Slide 8

## 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*

## Alternating Left and Right Finger Tapping 

**Alternating Left and Right Finger Tapping **

**~**** ****1992**

## Slide 12

## -

**EPISTAR**

** **

** **

** **

** **

**FAIR**

** **

** **

** **

**. . .**

**. . .**

**Perfusion**
**Time Series**

**-**

**-**

**-**

**-**

**Perfusion / Flow  Imaging**

## FAIR

**FAIR**

**EPISTAR**

## Resting ASL Signal

## Comparison with Positron Emission Tomography

- PET: H215O

- MRI: ASL

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Anatomic

- time

- _Anatomic_

- _Functional_

## Echo-Planar Imaging

**Echo-Planar Imaging**

## Slide 21

## Time (sec)

**Time (sec)**

## Slide 23

## Word stem completion

## Slide 25

## Latency

**Latency**

**Magnitude**

**+ 2 sec**

**- 2 sec**

## Regions of Interest Used for Hemi-Field Experiment

**Right Hemisphere**

**Left Hemisphere**

## Slide 28

## Hemi-field with 500 msec asynchrony

**Percent**

**MR**

**Signal**

**Strength**

**Time (seconds)**

**Average of 6 runs     Standard Deviations Shown**

## =

**+ 2.5 s**

**- 2.5 s**

**0 s**

**500 ms**

**500 ms**

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

**Left Hemifield**

**-**

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

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

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Single Shot Imaging

**T2* decay**

**EPI Readout Window**

**≈ ****20 to 40 ms**

## Multishot Imaging

**T2* decay**

**EPI Window 2**

## Partial k-space imaging

## 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 37

## Slide 38

## Slide 39

## BOLD

**BOLD**

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

## Anatomy

**Anatomy**

**BOLD**

**Perfusion**

## Hemodynamic Specificity

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

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

**Hemodynamic Specificity**

## 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.

## Why short is better than long

- [Oxy]

- The vascular response to
- prolonged neural stimulation

- The vascular response to
- brief  neural stimulation

- ~12 sec

- 1Malonek D, Grinvald A. Science 272, 551-4 (1996).
- 2Kim D-S, Duong T, Kim S-G. Nat Neurosci 3, 164-9 (2000).

- It is argued that fMRI cannot achieve submillimeter functional resolution because a saturated hyperoxic vascular response to neural activity spreads over many millimeters1,2.
- However, optical imaging has demonstrated that the hyperoxic response can yield well-localized maps when using short duration  stimuli (<5 sec)1.

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Temporal  S/N vs. Image S/N

**1400**
**1200**
**1000**
**800**
**600**
**400**
**200**

**0      200       400       600       800      1000     1200     1400**

**PHANTOMS**

**Image S/N**

**Temporal S/N**

***	******	******	******	******	******           ******	******	*****N. Petridou **

**Image S/N**

**Temporal S/N**

**SUBJECTS**

**Temporal  S/N vs. Image S/N**

## Slide 47

**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 ...)

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Motor Cortex

**Motor Cortex**

**Auditory Cortex**

## 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*

## Results – visual task

- Nonlinearity

- Magnitude

- Latency

## Results – motor task

- Nonlinearity

- Magnitude

- Latency

## Different stimulus “OFF” periods

- Stimulus
- timing

- BOLD
- Response

- measured

- linear

- Signal

- 2 s

- 3 s

- 4 s

- 8 s

- 16 s

*Brief stimulus OFF periods produce smaller decreases than expected*

## Sources of this Nonlinearity

- Neuronal
- Hemodynamic
- Oxygen extraction
- Blood volume dynamics

- Volume

- Flow In

- Flow Out

- Oxygen Extraction

## 5% CO2

**5% CO2**

**12% O2**

## 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.***

## Slide 59

## Neuronal Activation Input Strategies

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

## 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”

## Pushing the Envelope...

- Temporal Resolution
- Spatial Resolution
- Sensitivity and Noise
- Information Content
- Implementation

## Motion

**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 65

## Slide 66

## a.

**Time (sec)**

**a.**

**b.**

**c.**

## b.

**b.**

## Slide 69

## How to deal with Scanner Noise?

**Clustered volume acquisition**
**Talavage et al.**
**Silent sequences**

## Slide 71

## Slide 72

## Functional Imaging Methods / 3T Group	

**Staff Scientists:**
**Sean Marrett**
**Jerzy Bodurka**
**Post Docs:**
**Rasmus Birn**
**Patrick Bellgowan**
**Ziad Saad**
**Graduate Student:**
**Natalia Petridou**
**Summer Student:**
**Dan Kelley**
**Program Assistant:**
**Kay Kuhns**

**Functional Imaging Methods / 3T Group**

**August, 2000**