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Echo-Planar Imaging BOLD fMRI in Mice on a 9.4T Vertical Bore Microimager Govind Nair, Timothy Q Duong Center for Comparative NeuroImaging, Psychiatry.

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Presentation on theme: "Echo-Planar Imaging BOLD fMRI in Mice on a 9.4T Vertical Bore Microimager Govind Nair, Timothy Q Duong Center for Comparative NeuroImaging, Psychiatry."— Presentation transcript:

1 Echo-Planar Imaging BOLD fMRI in Mice on a 9.4T Vertical Bore Microimager Govind Nair, Timothy Q Duong Center for Comparative NeuroImaging, Psychiatry University of Massachusetts Medical School, Worcester, MA Grant supports Whitaker Foundation, RG American Heart Association, SDG NIH, NEI R01 EY NIH, 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% CO 2 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 -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 ( cm ID) – remote tuning and matching from top Shimming over an 8-mm thick slab; linewidth of Hz Single-shot, spin-echo EPI –TR / TE = 2500 ms / 38 ms (TE ~ T 2 at 9.4T) –FOV = 2 x 1 cm, matrix = 64x32 (312x312x600 m) –Nine 0.6-mm slices (0.15 mm gap) Paradigms –2 mins baseline, 2 mins CO 2 –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 –ROIs 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 ROIs without using an activation-map mask –Percent changes were computed

9 Hypercapnic Challenge Isoflurane level (% in air) Basal Respiratory rate (breaths per minute) Percentage increase during 10% CO ± 1933 ± ± 2432 ± ± 1526 ± ± 1016 ± ± 1819 ± 10

10 SE EPI and BOLD maps due to CO 2 challenge 15% 0% Single-shot No average

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

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

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% CO 2 Multi-segment EPI (78x78x500 m 2, 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 CurrentRRHRMABP baseline mA (387 32) (136 4) 6 mA (406 39) (141 6) * 8 mA * (419 44) ** * (148 8) ** * P = 0.01, ** P (Liu, Schmidt et al., in press 2004) RAT DATA: MABP traces and physiology under % isoflurane (n = 6, SD) 4mA 6mA 8mA 20 mmHg 10 s


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