# Presentation: 673583

## Pushing the Spatial, Temporal and Interpretive Limits of Functional MRI

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

## Categories of Questions 

**Categories of Questions **
**Asked with fMRI**

**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*****: time, motion, acoustic noise)**

## A Primary Challenge:

**...to make progressively more precise inferences using fMRI **
**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**

## Slide 5

## ?

**Neuronal**

**Activation**

**Hemodynamics**

**Measured**

**fMRI**

**Signal**

**?**

**?**

**Physiologic Factors**

## Physiologic Factors that Influence BOLD Contrast

- Blood oxygenation
- Blood volume
- Blood pressure
- Hematocrit
- Vessel size

**Coupling:**
**Flow & CMRO****2**

## Where and When?

**The resolution is determined by **
**the cerebral hemodynamics.**
**• ****Know the vasculature at which **
**you are looking.**
**(or)**
**• ****Normalize to the spatial variation **
**in the vasculature.**
**(or)**
**• ****Make several assumptions.**

## Slide 9

## Slide 10

## Slide 11

## -

**EPISTAR**

** **

** **

** **

** **

**FAIR**

** **

** **

** **

**. . .**

**. . .**

**Perfusion**
**Time Series**

**-**

**-**

**-**

**-**

**Perfusion / Flow  Imaging**

## FAIR

**FAIR**

**EPISTAR**

## BOLD

**BOLD**

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

## Anatomy

**Anatomy**

**BOLD**

**Perfusion**

## T1 - weighted

**T1 - weighted**

**T2* and T1***
**weighted**

**T2* weighted**

## Vascular Sensitization

**Vascular Sensitization**

## Spatial Normalization

**Hypercapnia**

**Spatial Normalization**

## Slide 19

## ,

**Finger **
**Movement**

**5% CO2**

**12% O2**

**Anatomical**

## Slide 21

## Finger Movement / 5% CO2

**Finger Movement / 5% CO2**

**Finger Movement**

## Hoge et al

**Hoge et al**

## Slide 24

## Slide 25

## Latency

**Latency**

**Magnitude**

**+ 2 sec**

**- 2 sec**

## Temporal Normalization

**Relative Timing**

**Temporal Normalization**

## Regions of Interest Used for Hemi-Field Experiment

**Right Hemisphere**

**Left Hemisphere**

## Slide 29

## Hemi-field with 500 msec asynchrony

**Percent**

**MR**

**Signal**

**Strength**

**Time (seconds)**

**Average of 6 runs     Standard Deviations Shown**

## Percent

**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**

**-**

## How Much?

**Central Issue:**
**Spatial and temporal neuronal firing integration **
**to create an fMRI signal change.**
***- is the hemodynamic response a linear system?***
***-what is the dynamic range?***

## Motor Cortex

**Motor Cortex**

**Auditory Cortex**

## Slide 36

## Slide 37

## Time (sec)

**Time (sec)**

## Stimululs - Duration Dependent Deviation 

- Stimululs - Duration Dependent Deviation
- from Linearity of the fMRI Response
- (Hemodynamic or Neuronal?)

- >linear

- linear

## How to get the brain to do what we want it to 

**do in the context of an fMRI experiment?**

**"Interesting"**
** ****Aspects of**
**MR Signal**

**Noise **
**&**
**Artifact**

## Neuronal Activation Input Strategies

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

## Slide 43

## Slide 44

## 2

- 3

- 4

- 5

- 6

- 7

- 8

- 9

- 10

- 11

- 12

- 13

- Overt Word Production

## Tongue Movement

- Jaw Clenching

## Event-Related fMRI Questions:

**1. What is the optimal ISI?**
**2. How does functional contrast **
** ****compare with “blocked” timing?**
***(Is the hemodynamic response a linear system?)***

## Contrast in Event Related fMRI

**Dependency on:**
**•****Inter-stimulus Interval (ISI)**
**•****Stimulus Duration (SD)**
**Comparison with:**
**•****Blocked strategies**
**•****Synthesized responses created using**
** ****convolution**

## Issues:

**1. ISI Issue**** **
**•****Shorter ISI provides more trials per unit time.**
**•****Shorter ISI causes overlap in hemodynamic **
**response, reducing dynamic range.**
**2. Contrast Issue**
**• ****Does signal behave like a linear system with **
**brief SD?**

## Experimental Methods

**•****Two imaging planes containing motor and **
**visual cortex.**
**•****EPI, 3.75 x 3.75 x 7 mm, TE = 40 ms, TR = 1 sec.**
**•****Time series duration = 360 images (6 minutes).**
**•****10 series compared:**
**Single Trial:**** SD = 2, ISI =  24, 20, 16, 12, 10, 8, 6, 4, 2.**
**Blocked: ****SD = 20, ISI = 20.**
**•****Subjects instructed to tap fingers when GRASS **
**goggles were on.**

**Experimental Methods**

## Visual Cortex

**20, 20**

**ISI, SD**

**12, 2**

**10, 2**

**8, 2**

**6, 2**

**4, 2**

**2, 2**

**ISI, SD**

## Motor Cortex

**Motor Cortex**

**20, 20**

**ISI, SD**

**12, 2**

**10, 2**

**8, 2**

**6, 2**

**4, 2**

**2, 2**

**ISI, SD**

## Motor Cortex

**ISI**

**ISI**

**Visual Cortex**

## Motor Cortex

**ISI**

**ISI**

**Motor Cortex**

**Visual Cortex**

## Contrast to Noise Images

**( ISI, SD )**

**S1**

**S2**

**Contrast to Noise Images**

## 20, 20

**20, 20**

**2, 2**

**( ISI, SD )**

**Motor**

**Visual**

**Relative differences in activation intensities**
**may reflect spatial differences in hemodynamic responsivity. (draining veins vs. capillaries).**

## Functional Contrast

**Functional Contrast**

**( Block design = 1 )**

## *

*****

**Response Synthesis**

**S = k t ****8.6 ****e**** - t / 0.547**

**Cohen, Neuroimage 6, 93-103 (1997)**

## Synthesized Responses

**Synthesized Responses**

**20, 20**

**ISI, Dur**

**12, 2**

**10, 2**

**8, 2**

**6, 2**

**4, 2**

**2, 2**

**ISI, Dur**

## Convolution

**ISI**

**Convolution**

## Functional Contrast

**ISI (sec)**

**1**

**32**

**1**

**32**

**SD (sec)**

**Functional Contrast**

## Functional Contrast

**Functional Contrast**

**( Block design = 1 )**

## Possible implications for interpretation of event-related

**Possible implications for interpretation of event-related**
**data using short, randomized ISI w/ deconvolution.****	**

**Dale AM, Buckner RL (1997), Human Brain Mapping, 5, 329-340.**

## Event - Related Functional Contrast

**Event - Related Functional Contrast**

**( Block design = 1 )**

**( ISI, SD )**

**Contrast to Noise Images**

## You can go

**You can go**
**even faster with**
**the assumption of **
**linearity...**

## If ISI is randomized,

**If ISI is randomized,**
**and if ON / OFF distribution**
**is 50%, the optimal average**
**ISI is as short as you can **
**make it.**

## Conclusions

**The fMRI signal is able to be ****calibrated****. Physiologic, neuronal, and pulse sequence calibration techniques are just starting to develop to complement pulse sequence advances.**
**-****spatial resolution**** < 0.5 mm**
**-****temporal resolution**** < 100 ms**
**-****information content:**** quantitative flow, CMRO2...**
**A large amount of additional information exists in the fMRI signal (i.e. fluctuations..).**
**To aid the development of calibration, more work needs to be done using extremely well understood neuronal activation (across several temporal, spatial, and intensity scales) to better characterize of the fMRI signal.**

## Slide 68