1. Perfusion MRI in GSK Study

2. Units Perfusion is measured in mL/100g of tissue/min, or units of CBF
Normal human gray matter is perfused at a rate of 50-60mL/100g/min

3. Measurable Parameters
CBF – Cerebral Blood Flow – The amount of blood moving through a given amount of tissue per unit time (can be absolute: aCBF, or relative: rCBF)
CBV – Cerebral Blood Volume – The amount of blood in a given amount of tissue at any time
MTT – Mean Transit Time – The average amount of time it takes any water molecule or particle of contrast agen to pass through the voxel vasculature

4. MRI Methods
Bolus Tracking - use of a contrast agent such as gadolinium as a tracer
Arterial Spin Labeling (ASL) - labels the water molecules of blood magnetically to use as a tracer

5. Arterial Spin Labeling Method
Tracer is a magnetic label applied to the water molecules in the blood
Magnetic label is produced by saturating or inverting the longitudinal component of the MR signal
The tagged water will pass into brain tissue and alter it’s longitudinal magnetization
A control image where no tagging is done is collected after each tagged image

7. Calculating CBF DM = Mcontrol – Mtag
A difference image is created from the control and tag image that is proportional to CBF.

8. Surround Subtraction
Perfusion images are calculated from a combination of the control and tagged images
Odd indexed images are tagged
Even indexed images are controls
Perfusion weighted time series
= {img[1] – (img[0]+img[2])/2}, {(img[1]+img[3])/2-img[2]}, …

10. Problems with Pulsed ASL
Slice profile effect alters the quality of the subtraction
Measurements are sensitive to the transit time of blood water between labeling and imaging sites

11. Solution
Add one or more spatial saturation pulse during the inversion time to saturate either the imaging slice or the tagging region. This is referred to as quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSSII)

12. QUIPSS RF Pulse Sequence
Slice selective in-plane presaturation applied to imaging slice
Inversion tag is applied
Second saturation pulse is applied to tagging region after a delay, TI1 (done only in QUIPSSII)
After additional delay, at time TI2, an image is acquired using single shot EPI after the inversion tag

13. GSK Study Basic Info
3 Study Days: A – Placebo, B – Ketamine, C – Ketamine&Lamotragine
2 Perfusion runs ~ 5minutes long
One before the bolus and one after the bolus
One Proton Density scan acquired

14. GSK Study Run Breakdown
Localizer
3D T1
T1 flash
Fixation
VOD
Fingertap
Proton Density
Perfusion
Fixation (bolus delivered)
VOD

15. Output Images in Analysis
dM – difference image (relative CBF)
BOLD
CBF (absolute CBF is calculated if Proton Density image was specified)