This proposal is technology-development driven. It also contains two pioneering applications of new technology for functional connectivity magnetic resonance imaging (fcMRI), which is also called resting-state fMRI (R-fMRI). Emphasis of this submission focuses on fMRI technology and analysis for rat brain because small- animal fMRI technology appears to be severely underdeveloped. We discovered fcMRI in human brain in 1995 and extended the discovery to rat brain at 9.4 T in 2008. Support is requested for continued development of technology and methodology for enhancement of fcMRI in rat brain. Spatial resolution for fcMRI will be 300 micron cubic or smaller, and it is this high resolution that makes this proposal exciting. We seek to achieve columnar and laminar fcMRI spatial resolution in rat brain cortex. Development of new and innovative radio frequency (RF) surface coils is proposed in Aim 1 that will allow the rat forepaw barrel subfield (FBS) to be imaged at extremely high resolution as described in the detailed studies of Aim 2. These coils will be developed and carefully compared. The best will be used in further studies. The FBS is a group of 23 cortical columns, or barrels, that provide the sensory representation of the forepaw. We have discovered that these columns can be electrically stimulated, one by one, using very small bipolar electrodes placed on the forepaw. Electrodes will be placed at eight locations, which will then be stimulated in pseudorandom manner. Seed voxels at each laminar level are defined for each column by fMRI, and connectivity studies are carried out between those voxels. We carry out fcMRI between, and possibly within, columns both intra- and inter- hemispherically. This is new and highly innovative, and the preliminary data are solid. Furthermore, two multi-coil arrays are proposed in Aim 1 that enable the whole resting-state rat brain connectome to be acquired as described in the detailed studies of Aim 3. It is noted that there appear to be no reports of multi-coil usage in rat brain in the literature, making this coil development highly innovative. Two new and highly innovative pulse sequences developed in this laboratory for human imaging will be translated to rat-brain usage at 9.4 T. Temporal acceleration is obtained by enhanced rate of acquisition of each image slice and by parallel slice acquisition (which uses one of the new sequences) working in concert. In addition, a cluster of relaxation parameters will be obtained for each voxel using the other new sequence. These parameters will allow segmentation by tissue type: only gray matter will contribute to the rat connectome-an approach that is believed to be novel and innovative. The impact of the proposal is twofold. First, it contributes to the foundation of fcMRI, which is a rapidly growing field. This growth is occurring because the entire brain can be probed, which is not possible using task-activation methods. And, second, it strengthens the use of rat models of human disease because it enhances functional imaging of the central nervous system (CNS).

Public Health Relevance

Animal models of disease are widely used in medical research, and this proposal will enhance the ability of scientists to understand the role of the brain in these diseases. Functional connectivity MRI (fcMRI) will be extended in rat brain in two ways: acquisition of the pattern of connectivity across the entire rat brain and establishment of the limits of high resolution. New basic information about mammalian brain connectivity will be obtained that seems impossible to obtain in human brain because of technology limitations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000215-26
Application #
8708072
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Liu, Christina
Project Start
1986-01-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
26
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Biophysics
Type
Schools of Medicine
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Rowe, Daniel B; Bruce, Iain P; Nencka, Andrew S et al. (2016) Separation of parallel encoded complex-valued slices (SPECS) from a single complex-valued aliased coil image. Magn Reson Imaging 34:359-69
Pawela, Christopher; DeYoe, Edgar; Pashaie, Ramin (2016) Intracranial Injection of an Optogenetics Viral Vector Followed by Optical Cannula Implantation for Neural Stimulation in Rat Brain Cortex. Methods Mol Biol 1408:227-41
Mett, R R; Sidabras, J W; Hyde, J S (2016) Meta-metallic coils and resonators: Methods for high Q-value resonant geometries. Rev Sci Instrum 87:084703
Hudetz, Anthony G; Liu, Xiping; Pillay, Siveshigan (2015) Dynamic repertoire of intrinsic brain states is reduced in propofol-induced unconsciousness. Brain Connect 5:10-22
Li, Rupeng; Liu, Xiping; Sidabras, Jason W et al. (2015) Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step towards whole brain functional connectivity imaging. PLoS One 10:e0119450
Jesmanowicz, Andrzej; Nencka, Andrew; Hyde, James S (2014) Direct radiofrequency phase control in MRI by digital waveform playback at the Larmor frequency. Magn Reson Med 71:846-52
Li, Chenxuan; Li, Zhixin; Ward, B Douglas et al. (2014) Enhancement of resting-state fcMRI networks by prior sensory stimulation. Brain Connect 4:760-8
Li, Rupeng; Machol 4th, Jacques A; Liu, Xiping et al. (2014) C7 nerve root sensory distribution in peripheral nerves: a bold functional magnetic resonance imaging investigation at 9.4 T. Muscle Nerve 49:40-6
Li, Rupeng; Hettinger, Patrick C; Liu, Xiping et al. (2014) Early evaluation of nerve regeneration after nerve injury and repair using functional connectivity MRI. Neurorehabil Neural Repair 28:707-15
Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter et al. (2014) Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats. Brain Connect 4:523-34

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