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Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI.

Publication ,  Journal Article
Howles, GP; Qi, Y; Rosenzweig, SJ; Nightingale, KR; Johnson, GA
Published in: J Vis Exp
July 12, 2012

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents. In AIM MRI, Mn(2+) acts a calcium analog and accumulates in depolarized neurons. Because Mn(2+) shortens the T1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn(2+) clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn(2+) does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice. One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage. Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response. To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.

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Published In

J Vis Exp

DOI

EISSN

1940-087X

Publication Date

July 12, 2012

Issue

65

Start / End Page

e4055

Location

United States

Related Subject Headings

  • Mice
  • Manganese
  • Magnetic Resonance Imaging
  • Functional Neuroimaging
  • Echoencephalography
  • Cations, Divalent
  • Brain
  • Blood-Brain Barrier
  • Animals
  • 3101 Biochemistry and cell biology
 

Citation

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ICMJE
MLA
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Howles, G. P., Qi, Y., Rosenzweig, S. J., Nightingale, K. R., & Johnson, G. A. (2012). Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI. J Vis Exp, (65), e4055. https://doi.org/10.3791/4055
Howles, Gabriel P., Yi Qi, Stephen J. Rosenzweig, Kathryn R. Nightingale, and G Allan Johnson. “Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI.J Vis Exp, no. 65 (July 12, 2012): e4055. https://doi.org/10.3791/4055.
Howles GP, Qi Y, Rosenzweig SJ, Nightingale KR, Johnson GA. Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI. J Vis Exp. 2012 Jul 12;(65):e4055.
Howles, Gabriel P., et al. “Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI.J Vis Exp, no. 65, July 2012, p. e4055. Pubmed, doi:10.3791/4055.
Howles GP, Qi Y, Rosenzweig SJ, Nightingale KR, Johnson GA. Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI. J Vis Exp. 2012 Jul 12;(65):e4055.

Published In

J Vis Exp

DOI

EISSN

1940-087X

Publication Date

July 12, 2012

Issue

65

Start / End Page

e4055

Location

United States

Related Subject Headings

  • Mice
  • Manganese
  • Magnetic Resonance Imaging
  • Functional Neuroimaging
  • Echoencephalography
  • Cations, Divalent
  • Brain
  • Blood-Brain Barrier
  • Animals
  • 3101 Biochemistry and cell biology