Why high-field MRI? Benefits of high-field MRI. Signal-to-noise ratio (SNR) Contrast (anatomical & functional) 8 x 8 x 8 mm 3 4 x 4 x 4 mm 3

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Why high-field MRI? 8 x 8 x 8 mm 3 4 x 4 x 4 mm 3 2 x 2 x 2 mm 3 1 x 1 x 1 mm 3 Voxel volume 2 x 2 x 2 mm 3 = 8 Voxel volume 1 x 1 x 1 mm 3 = 1 Benefits of high-field MRI Signal-to-noise ratio (SNR) Contrast (anatomical & functional) 1

Outline High-resolution vascular imaging High-resolution fmri applications Anatomical contrast @ 7T MRI Clinical applications of @7T MRI High Resolution Vascular Imaging coronal A T 1 -weighted 3D gradient echo acquisition. TR/TE = 32.4/5.5 ms readout bandwidth 20 khz FOV: 20 x 20 x 5mm Matrix: 256 x 256 x 32 Image resolution: 0.078 x 0.078 x 0.156 mm San time: acquisition time 4:25 min/scan, total scan time 35:20 min (n=8). Veins are dark due to elevated concentration of deoxyhemoglobin (BOLD) axial Bolan, et al. NeuroImage 2006 High Resolution Vascular Imaging (Time-of-flight / inflow effects) coronal In a T 1 -weighted sequence, long T 1 spins are saturated because they don't have time to recover Excitation slab Fresh blood that flows into the slice is fully relaxed, and therefore bright axial axial Bolan, et al. NeuroImage 2006 2

High Resolution Vascular Imaging In a T 1 -weighted sequence, long T 1 spins are saturated because they don't have time to recover (Time-of-flight / inflow effects) coronal Arteries are bright due to unsaturated fresh blood fast inflow into slab Veins are dark due to elevated concentration of deoxyhemoglobin (BOLD) sagittal axial Bolan, et al. NeuroImage 2006 High Resolution Vascular Imaging (Time-of-flight / inflow effects) In a T 1 -weighted sequence, long T 1 spins are saturated because they don't have time to recover Vessel Classification Arteries are bright due to unsaturated fresh blood fast inflow into slab Veins are dark due to elevated concentration of deoxyhemoglobin (BOLD) axial Veins Arteries Bolan, et al. NeuroImage 2006 In-vivo High Resolution Vascular Imaging Maximum Intensity Projections (MIP) MIP of the 3D subtraction (Pre/Post MION) Bolan, et al. NeuroImage 2006 3

High Resolution Vascular Imaging (Time-of-flight / inflow effects) 3D Vessel Reconstruction Vessel Classification Veins Arteries Bolan, et al. NeuroImage 2006 High Resolution Vascular Imaging (SEM ) Ex-vivo Weber et al., Cereb. Cortex 2008 Scanning electron micrographs of a vascular corrosion cast from monkey visual cortex (superior temporal gyrus) BOLD signal and the underlying vascular system Multi slice BOLD fmri: Voxel size: 0.25 x 0.25 x 0.5 mm Harel et al, Front Neuroenergetics 2010 4

Anatomical Image Functional Image Ogawa, Tank, Menon, Ellermann, Kim, Merkle, Ugurbil. PNAS.1992 Advantages of high-field for fmri 4 Tesla 7 Tesla Yacoub, 2003 Spatial Specificity of fmri Signals SE-BOLD 7T; 1 x 1 x 2 mm Yacoub et al., 2003 5

Cortical Lamina Surface I II / III IV V VI White Matter gray matter / tissue Brodmann's "areas" Brodmann, 1909 Cell size Cell type Cell density Korbinian Brodmann (1868-1918) High Resolution BOLD fmri Surface GE-BOLD 0.7 1mm SE-BOLD White Matter 0.5 0.1 0.1 Cat Magnet: 9.4T In-plane Resolution: 150 x 150 µm 2 Harel et al, Harel NeuroImage et al. 2006 Low magnification photographs Histology (Nissl) High magnification I II & III VI V IV Harel et al, NeuroImage 2006 6

GE-BOLD Layer Specificity of BOLD fmri (, S) Harel et al, Harel NeuroImage et al. 2006 In-vivo High Resolution Vascular Imaging coronal axial MIP of the 3D subtraction (Pre/Post MION) Bolan et al, NeuroImage 2006 GE-BOLD Layer Specificity of BOLD fmri (, S) SE-BOLD Harel et al, Harel NeuroImage et al. 2006 7

Anatomical Image Functional Image Ogawa, Tank, Menon, Ellermann, Kim, Merkle, Ugurbil. PNAS.1992 Functional-units (cortical columns) are believed to be the basic computational unit in the brain Surface White matter LGN Neurons with similar response properties tend to cluster together in columns extending through the entire cortex Optical Imaging - Monkey Recording Chamber 8

Optical Imaging - Monkey R LR LR L Monocular stimulation Ts o et al., 1990 Anatomical (post-mortem) ODC Spatial Organization Horton & Hedley-Whyte, 1984; Horton, 2006 Cheng et al., 2001 Functional (fmri) Menon et al., 1997 Dechent & Frahm, 2000 Goodyear & Menon, 2001 Cheng et al., 2001 SE-BOLD 7 T ODC Spatial Organization Monocular stimulation Cheng et al., 2001 3 cm EPI Image 1 mm Yacoub et al., 2007 Image resolution: 0.5 x 0.5 x 3 mm 9

Electrophysiological Recording Cell Discharge Ice cube model orientations ODC Hubel & Wiesel, 1968 Optical Imaging - Cat Pinwheels Ice cube model orientations Hubel & Wiesel, 1968 ODC Bonhoeffer & Grinvald, 1991; 1993; Blasdel 1992 Phase Map - fmri Orientation Map Optical Imaging 0 Phase 2π Bonhoeffer & Grinvald, 1991; 1993 Does the fmri-phase Map Reveal Orientation Specific Activation Zones? 1 mm 10

1. Radial arrangement of orientation columns (pinwheels) 2. Pinwheels rotate in opposite directions 3. Pinwheels centers (singularities) tend to concentrated in the center of ocular dominance columns 4. Iso-orientation lines intersect the borders between ocular dominance borders at right angles (linear zones) Clockwise Counter Clockwise Optical Imaging - monkey Ipsi- Contra- Blasdel, JNS 1992 Bartfeld & Grinvald, PNAS 1992 Obermayer & Blasdel, JNS 1993 Crair et al., J Neurophysiol. 1997 Hubener et al., JNS 1997 fmri - human 0 Phase Optical Imaging - cat 2π 1 mm Yacoub, Harel & Ugurbil, PNAS 2008 ODC Phase Map 1 mm 1 mm 11

Phase Map Clockwise Counter Clockwise Scalebar = 0.5 mm 0 2π Phase Yacoub, Harel & Ugurbil, PNAS 2008 ~4 mm ~4 mm Yacoub, Harel & Ugurbil, PNAS 2008 Obermayer & Blasdel, JNS 1993 Zimmermann et al., 2011 12

Anatomical Imaging at Ultra-high Field MRI Benefits of high-field (7 Tesla) MRI 1.5 T (clinical) 7 T Noam Harel, University of Minnesota / CMRR Susceptibility-Weighted Imaging (SWI) Phase contrast in the primary visual cortex Duyn J et al. PNAS 2007;104:11796-11801 13

Anatomical contrast @ 7 Tesla T 1 W T 2 W SWI STN SN RN STN: subthalamic nucleus SN: substantia nigra RN: red nucleus Abosch, et al., Neurosurgery 2010 Susceptibility-Weighted Imaging @ 7T STN SN Magnet: 7T Resolution: 0.4 x 0.4 x 0.8 mm STN = Subthalamic Nucleus SN = Substantia Nigra Susceptibility-Weighted Imaging @ 7T Schaltenbrand and Wahren Atlas (Ex-vivo) GPe GPi SWI @ 7T (In-vivo) GPe GPi Lamina pallidi medialis GP = Globus pallidus Abosch, et al., Neurosurgery 2010 14

Thalamus level Atlas (Ex-vivo) SWI @ 7T (In-vivo) Vim = Ventralis intermedius (motor thalamus) Vc = Ventral caudalis Abosch, et al., Neurosurgery 2010 Detections of Brain Structures with 7 Tesla MRI SWI Patient-Specific Anatomical Model T 2 W Thalamus (Tha) Subthalamic nucleus (STN) Substantia nigra (SN) Red nucleus (RN) Globus Pallidus GPi GPe A surgically implanted medical device - brain pacemaker Sends electrical impulses to the brain FDA approved DBS applications: Movement disorders, including: Parkinson s disease Essential tremor Humanitarian Device Exemption (HDE): Obsessive-Compulsive Disorder (OCD) Major Depression Epilepsy Dystonia Under clinical trials: Alzheimer's disease Tourette s Syndrome Over 120,000 DBS cases worldwide 15

Limitation of Current Procedure 2D - Stereotactic atlas Microelectrode recording (MER) Patient awake during surgery Consensus Coordinates (STN): Lateral 12 mm Posterior to MCP 4 mm Below MCP 5 mm Range (8.7 mm 14.5 mm) (3.5 mm posterior to 0.5 mm anterior) (1.3 mm 6 mm) Success of DBS surgery is critically dependent on the precise placement of the electrodes into the target structures DBS STN SN RedN Duchin, Sapiro, Vitek, Harel U of Minnesota / CMRR Essa Yacoub Patrick Bolan Steen Moeller Christophe Lenglet Yuval Duchin Kamil Ugurbil Duke University Guillermo Sapiro Neurosurgery Aviva Abosch Jon McIver Neurology Jerrold Vitek Work supported in part by the National Institutes of Health (R01NS085188, P41RR08079, P30 NS057091, R01 NS081118) the W.M. Keck Foundation, and MIND institute. 16