Functional MRI: Physiology and Methodology

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. Functional Map Stimulation/Task (MRI) Neural Activity Mapping Brain Functions Pre-synaptic activity Post-synaptic activity Action potentials Blood flow Blood volume Blood oxygenation Vascular Response

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

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

5. 5 mm 25 x 12 x 2 µm ~ 20ms/frame 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 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. Single-neuron Activities Cortical Column Model in V1 Ocular Dominance Columns Color sensitive regions Gray matter (1.5 – 3 mm) Orientation columns Hubel & Wiesel, 1968

8. Conventional BOLD fMRI 3.0 % 0.3 2 mm With contrast agent, iron oxide particle Reduce large vessel signals fMRI without and without contrast agent (Cat visual stimulation, 156 x156 x 1000 m) (Zhao, Wang, Hendrich, Ugurbil & Kim, Neuroimage, 30, 1149-60, 2006)

9. Left Right Marginal gyrus (mg) Lateral sulcus (LS) Coronal plane mg LS WM 5 mm A 2 mm L -30 -180 (a.u.) (Zhao, Wang, Hendrich & S-G. Kim, Neuroimage, 27, 416-24, 2005)

10. ( 570 nm) Optical imaging MRI 5 mm 5 mm A A A M M M fMRI vs. Invasive Optical Imaging Left Right LS mg SUPS SPL 1 cm 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 0 Signal intensity (arbitrary unit) optical imaging -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 V -10 0 +10 Signal intensity (arbitrary unit)

13. D A M L P V 1 mm 3D architecture of orientation columns With Shigeru Tanaka at RIKEN, sfn 366.22, 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 Kristy Hendrich Ping Wang Michelle Tasker Shafiq Abedin Hiro Fukuda Alberto Vazquez 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. 3.125 mm #0 #1 #2 #3 Left Right Midline Coronal view #0 #1 #2 #3 #4 #5 #6 #7 2.0x2.0 cm^2 #5 #6 #7 #4 Multi-slice imaging of orientation columns 3.5x2.2 cm2 With Shigeru Tanaka at RIKEN sfn 366.22, 2008

17. Electric Activity Measurements