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  1. Echo-Planar Imaging BOLD fMRI in Mice on a 9.4T Vertical Bore MicroimagerGovind Nair, Timothy Q DuongCenter for Comparative NeuroImaging, PsychiatryUniversity of Massachusetts Medical School, Worcester, MA 01655Grant supportsWhitaker Foundation, RG-02-0005 American Heart Association, SDG-0430020NIH, NEI R01 EY014211NIH, NINDS R01 NS45879

  2. Introduction • Longitudinal imaging of transgenic mice and mouse disease models allows studies to be performed over their entire life span. • Narrow-vertical bore magnets (microimagers) are well suited for imaging mice • low cost • availability at high fields • availability of high-performance gradients • While anatomical imaging is readily available, fMRI in mice on microimagers remains a major challenge

  3. Introduction • Mice fMRI on microimager had been reported using conventional gradient-echo sequence (Arhens 2001; Huang 1996) and fast spin-echo with exogenous contrast agent sequence (Mueggler 2003) • These sequences generally yield • Reduced temporal resolution • Reduced SNR per unit time • Reduced sensitivity to BOLD contrast • Increased physiological noises • Echo-planar imaging overcomes these problems albeit • Increased susceptibility artifact • Harder to implement due to larger eddy current (small bore) • Poor shimming capability on small-bore magnets

  4. Introduction • Other challenges include • Limited spaces for physiological monitoring • More difficult to use mechanical ventilation • Increased susceptibility-induced signal loss due to small brain size and larger air-tissue interfaces • The goal of this study was • To develop a sensory-stimulation mouse model for fMRI studies • Explore echo-planar imaging for fMRI on a 9.4 T microimager

  5. Methods • Mouse head immobilized with ear, tooth and shoulder bars • Anesthetized with isoflurane • Spontaneously breathing mice • Monitored respiration via a transducer • Maintained body temperature at 37 ± 0.5 C

  6. Methods • Three sets of experiments were performed: • Graded isoflurane (0.25, 0.50, 0.75, 1.0, 1.25%) were explored using 10% CO2 to determine the optimal BOLD CNR (n = 9) • Hindpaw electrical stimulation (1-7 mA) on mice anesthetized under the optimal isoflurane level (n = 6) • Stimulation were explored in details with 4 and 6 mA and under 0.75% and 1.0% isoflurane (n = 5) • Relatively high currents were used because isoflurane is a potent anesthetic, relative to the widely used a-chloralose • Bench top observations were also observed in some of the hindpaw-stimulation animal and four additional animals

  7. Imaging Parameters • 9.4 T / 89 mm vertical magnet, 100 G/cm gradient (45 mm ID) • Surface coil (1.2-1.5 cm ID) – remote tuning and matching from top • Shimming over an 8-mm thick slab; linewidth of 30-45 Hz • Single-shot, spin-echo EPI • TR / TE = 2500 ms / 38 ms (TE ~ T2 at 9.4T) • FOV = 2 x 1 cm, matrix = 64x32 (312x312x600 mm) • Nine 0.6-mm slices (0.15 mm gap) • Paradigms • 2 mins baseline, 2 mins CO2 • 2 mins baseline, 1 mins stimulation, 2 mins baseline • Anatomy obtained with similar parameters but at higher resolution

  8. Data analysis • Hypercapnia • BOLD percent changes were calculated from a whole-brain ROI • BOLD contrast-to-noise ratio (CNR) was computed • Hindpaw stimulation • Cross-correlation maps were calculated • ROI’s of the hindpaw primary sensory cortex was drawn with reference to the average of all activation maps and anatomy • Time courses of different conditions were obtained from the same ROI’s without using an activation-map mask • Percent changes were computed

  9. Hypercapnic Challenge

  10. SE EPI and BOLD maps due to CO2 challenge Single-shot No average 15% 0%

  11. Hypercapnic Stimulation Hypercapnic challenge (N = 9) (N = 1)

  12. Hindpaw stimulation (Group II, n = 4) 0.9 CC 0.3 Stimulation

  13. Hindpaw stimulation (Group III, n = 5)

  14. Work in progress: GE EPI and segmented EPI Gradient-echo EPI Gradient-echo BOLD responses to 10% CO2 Multi-segment EPI (78x78x500 mm2, no signal average)

  15. Conclusions • Implemented spin-echo EPI for fMRI study • Developed a mouse model for sensory stimulation fMRI study • Optimized isoflurane concentration • Stimulation currents • These optimal parameters are in good agreement with an isoflurane-anesthetized sensory-stimulation model in rats where MABP, HR and RR and blood-gas measurements were carefully monitored. • Improvement in spatial resolution and BOLD contrast are under investigation.

  16. 4mA 6mA 8mA 20 mmHg 10 s RAT DATA: MABP traces and physiology under 1.15-1.25% isoflurane (n = 6, SD) * P = 0.01, ** P  0.008 (Liu, Schmidt et al., in press 2004)