1. Functional MRI: Physiology and Methodology
Seong-Gi Kim
Department of Radiology and Neurobiology
Univ. of Pittsburgh
Supported by NIH (NS44589, EB003324, EB003375), and
McKnight Foundation

2. Mapping Brain Functions
Stimulation/Task
Functional Map
(MRI)
Neural Activity
As you know very well, functional brain mapping relies on many events from stimulation to detecting signal changes in brain. Stimulation induces neural activity at the localized brain area, then induces hemodynamic changes in blood vasculature such as blood flow, -> detect signal changes using MRI or PET.
Pre-synaptic activity
Post-synaptic activity
Action potentials
Blood flow
Blood volume
Blood oxygenation
Vascular Response

3. Blood oxygenation level
Vascular Structure
Arteries
Capillaries
Veins
Blood oxygenation level
~1.0
~0.6
Distance

4. Blood oxygenation level
Vascular Structure
Arteries
Capillaries
Veins
(Task -> oxygen supply overcompensates
oxygen utilization)
Blood oxygenation level
~1.0
~0.6
Distance
(Fox et al., 1988)

5. Lab’s Research Facility
MR Laboratory
9.4 Tesla, 31-cm bore MR instrument
Visual and electrical stimulation equipment
MR-compatible EEG
Life-supporting equipment
Access to human 3 and 7 T MR systems
Physiology Lab
5 mm
25 x 12 x 2 µm
~ 20ms/frame
Tail tail vein of GFP mice was catheterized for the administration of rhodamine-B dextran (MW of 70 kDa), an intra-vascular fluorescent plasma dye (Figure 2A). -green: neurites (dendrites and axons, not cell bodies because of upper cortical layers)
Invitrogen, Texas Red: excitation/emission maxima of ~595/615 nm
Two-photon laser scanning microscope
Intrinsic optical imager
16-channel multi-unit recording system
Laser Doppler flowmeter
Oxygen polarographer
230 x 230 µm

6. Lab’s Research Direction
Quantification of fMRI Signals
Anatomical source of fMRI: Intra- vs. extravascular
large vs. small vessels; arterial vs. venous vessels
2. Physiological source of fMRI:
neural activity, metabolic response, hemodynamic response
Technological Advances
Development and characterization of various fMRI techniques
(SE BOLD, CBF, CBV, arterial CBV, CMRO2, diffusion, etc)
Pushing limits of spatial and temporal resolution

7. Cortical Column Model in V1
Single-neuron Activities
Ocular
Dominance
Columns
Color sensitive
regions
Gray matter
(1.5 – 3 mm)
Orientation columns
Hubel & Wiesel, 1968

8. fMRI without and without contrast agent
(Cat visual stimulation, 156 x156 x 1000 m)
2 mm
Conventional BOLD fMRI
0.3
3.0 %
With contrast agent, iron oxide particle
Reduce large vessel signals
(Zhao, Wang, Hendrich, Ugurbil & Kim, Neuroimage, 30, , 2006)

9. Coronal plane Left Right mg WM 5 mm A 2 mm L LS Marginal gyrus (mg)
Lateral sulcus (LS)
Marginal gyrus (mg) mg LS WM
5 mm A
2 mm L
-30
-180 (a.u.)
(Zhao, Wang, Hendrich & S-G. Kim, Neuroimage, 27, , 2005)

10. fMRI vs. Invasive Optical Imaging
Left
Right LS mg
SUPS
SPL
1 cm
Optical imaging
5 mm M A
( 570 nm)
MRI M A
5 mm
Comparison between fMRI and optical imaging is not trivial. 1-mm thick fMRI slice is selected in the middle of the cortex (dashed rectangles), while optical imaging data is acquired at the surface of the cortex. (note mg, maginal gyrus where visual cortex exists; LS, lateral sulcus).
To coregister images acquired by fMRI and optical imaging, pial vascular pattern just above the fMRI imaging slice was used.
(move to a next slide) In vessel-weighted MRI, you can see pial vessels as well as intracortical veins (dark spots). It is quite straightforward to obtain vessel-weighted optical images.
(move to a next slide) After moving around images to match vessel patterns, we can find vessel pattern in the ROI is well-matched.
(move to a next). Expand ROIs (move to a next), trace vessel tress in optical image (move to a next) overlay on MRI data. Vessel patterns are well-matched. This is how we can coregister between MRI and optical data.
Note that 6 cats were compared to OIS. M A
1 mm
(Fukuda, Moon, Wang & Kim, J Neurosci, 26:11821–11832, 2006)

11. Iso-orientation maps measured by fMRI vs. optical imaging
(in the same cat) +1
fMRI
Signal intensity (arbitrary unit)
optical imaging
This is one animal data.
Dark spots indicate CBV increase during the stimulation shown in right corner orientation. 45, 90, 135, 0 degree. (just in case, the bright spots indicates the orthogonal stimulation-induced area).
Both maps are quite similar. To help comparison between these two, we marked patched and bothers based on fMRI, and then overlain on optical images
(move to a next). This clearly shows that both maps agree very well, indicating that larger plasma-volume change area co-register larger RBC volume change. -1
1 mm
(Fukuda, Moon, Wang & Kim, J Neurosci, 26:11821–11832, 2006)

12. Iso-orientation maps in the medial area using CBV-weighted fMRI
5 mm D A P
SPL: spleinal sulcus V
SPL
-10
+10
Signal intensity (arbitrary unit)

13. 3D architecture of orientation columnsV M L A P
1 mm
With Shigeru Tanaka at RIKEN, sfn , 2008

14. My future plan and interest
Collaborative Research Efforts
Implementation of new fMRI methodologies into human fMRI research
2. Clinical neuroimaging research

15. Physiology/Optical Imaging Research Staff
Hiro Fukuda
Alberto Vazquez
Kristy Hendrich
Ping Wang
Michelle Tasker
Shafiq Abedin
MRI/Biophysics
External Collaborators
Tao Jin
Tae Kim
Paul Schornack
Cecil Yen
Yuquang Meng
Justin Crowley at CMU
Shigeru Tanaka at RIKEN
Peter Strick at Pitt

16. Multi-slice imaging of orientation columns#0 #1 #2 #3 #4 #5 #6 #7
2.0x2.0 cm^2
3.125 mm
Midline
Coronal view
Left
Right
3.5x2.2 cm2 #0 #1 #2 #3 #4 #5 #6 #7
Orientation column-resolution fMRI was performed on cat visual cortex at 9.4T. The normal adult cat was anesthetized with isoflurane ( %) and immobilized with pancuronium bromide (0.2 mg·kg-1·hr-1, i.v.).
The imaging positions were selected in the region of dorsal surface and less large surface veins, based on high-resolution 3D anatomical images. fMRI data were acquired using the multi-slice 2D gradient-echo EPI sequence with parameters: TR =2.0s, TE =10ms, matrix=128×128, and FOV=2×2cm2, following an intravascular bolus injection of a dextran-coated monocrystalline iron oxide nanoparticles (MION) contrast agent (20mg Fe/kg body weight).
Eight overlapping 0.5-mm thick slices (0.4mm inter-slice gap) covered a 2.8mm slab. For visual stimulation, high-contrast square-wave full-field moving gratings (0.15cpd, 2Hz, movement direction reversal per 0.5s) were presented binocularly with 8 consecutive orientations (22.5º increments, 10s each) presented without a gap between different orientations for one cycle (80s). One stimulation cycle was repeated ten times continuously (total 800s per run). Twenty fMRI runs were performed for signal averaging.
With Shigeru Tanaka at RIKEN
sfn , 2008

17. Electric Activity Measurements