While challenges of SNR, hardware, and pulse sequence have limited the penetration of MRSI into clinical use, it remains among the most sensitive avenues towards assessing cerebral function and an important motivation for ongoing 7T development. However at any field strength, MRSI has challenges for spectral quality, acceptable acquisition time and spatial coverage. Specifically, while 3T MRSI has reported excellent SNR for NAA in supraventricular locations, there remain acknowledged problems for spectral quality in critical brain regions including the temporal and frontal lobes. 7T MRS has shown the expected doubling in SNR, which with the >2-fold greater spectral resolution effectively gives a total 16x reduction for scan time in comparison to 3T. However, problems at 7T focus on rf coil technology and B0 inhomogeneity. At 300MHz, the dielectric constant of tissue results in marked axial and longitudinal B1 inhomogeneities, simultaneous to a linear increase in required power for equivalent B1 generation. With a goal of developing and implementing MR spectroscopic imaging at 7T, our group has developed a transceiver detector which as used with RF shimming, has shown excellent performance at 7T. In collaboration with Resonance Research Inc., we have also shown that with higher order shim mapping and corrections, outstanding field homogeneity can be achieved over extended brain regions. Thus far this success has been primarily achieved over single slice regions. In this project, we will continue to develop this work for wide brain and multi-slice MRSI at 7T. This will be achieved through Aim 1 that extends the longitudinal coverage of the transceiver and further improves large volume Bo homogeneity, and Aim 2 which develops the pulse sequences (B1 based localization, Hadamard and SENSE encoding with the J-refocused acquisition), our goal being high SNR multi-slice spectroscopic imaging with low SAR (~2W/kg). Because methodologic development ideally occurs with real-world targets, we will test these developments with the challenging problem of neocortical epilepsy (NE). Since many NE patients are clinically complex, their evaluation commonly requires intracranial EEG (icEEG), a neurosurgical procedure where intracranial electrodes are used to localize seizures. For this process, it is clear that as much advanced knowledge on where to place electrodes is needed, so as to not "miss" the seizure onset zone. Yet even with this complex process, the post-surgical outcome is that ~40-50% of patients continue with significant seizures. With the variable etiologies in NE, there are major challenges for MRSI coverage (seizures can arise from any cortical location), volume resolution (typical size of ictal onset zone), and optimal metabolite pattern (is glutamate better than NAA). These unknowns likely explain why MRSI is not routinely used at 3T, but even in anatomically well defined medial temporal lobe epilepsy, there are spectral quality problems at 3T.
In Aim 3, we will test the hypothesis that in regions of seizure onset and propagation (as defined by icEEG) the NAA/Cr and Glu/Cr will be abnormal, thus determining the typical voxel size needed for such identification, and whether NAA or glutamate may be more accurate. To bring this work into greater implementation, Aim 4 will take the parameters identified at 7T into a collaboration with O Gonen PhD, New York Univ., a leader in the development and application of 3T wide brain coverage MRSI. We will compare extended volume coverage MRSI at 3T and 7T in healthy controls and in a limited group of patients, allowing us to define the optimum methods at 3T to achieve identification of ictogenic regions. This project proposes a coordinated development in hardware and pulse sequences for 7T MRSI. We believe that this project's impact is broad, not just for improved neurosurgical management of NE, but also for improved imaging and MRSI at 3 and 7T. As stated, 3T MRSI, while successful for supra- ventricular regions, is inconsistent in the temporal lobes. This will improve with our proposed work in higher order shims and algorithms that optimally correct for and redistribute B0 homogeneity. At 7T, the transceiver work is critical as presently there is no clear solution to the problem of homogeneous and extended rf (~20uT) coverage. Thus while the impact of this project is clearly for 7T MRSI, the proposed work in B1 methods and B0 shimming will be highly relevant for many aspects of high field MR, both 7 and 3T.

Public Health Relevance

Although human sized ultra high field (7T+) MR systems have been available since the late 1990s, their scientific and clinical impact has been limited. Most of the limitation arises from technical challenges resulting from the increased field strength, i.e., the existing (lower field) strategies for the signal detector (RF coil) and field homogeneity have been insufficient for immediate extrapolation to 7T. This problem is particularly acute for MR spectroscopic imaging, for which data quality is expected to substantially benefit from the higher field. With a goal of developing and implementing MR spectroscopic imaging at 7T, our group has developed a transceiver detector which when implemented with RF shimming, has shown excellent performance at 7T. In collaboration with Resonance Research Inc., we have also shown that with higher order shim mapping and corrections, outstanding field homogeneity can be achieved over extended brain regions. Thus far however, this success has been primarily achieved over single slice regions. In this project, we will continue to develop this work for wide brain and multi- slice MRSI at 7T. Because methodologic development ideally occurs with real-world targets, we will test these developments with the challenging problem of neocortical epilepsy. As a disorder for which highly effective (surgical) treatment exists and is commonly considered, the major challenge in neocortical epilepsy is the anatomic localization of seizure onset. For clinical evaluation however, it is fairly common for patients to require intracranial EEG monitoring, a 7 to 10day+ evaluation that begins with the neurosurgical placement of EEG electrodes (typically 50 to 200+ contacts used) on the brain surface to sensitively record seizures. It is clear that as much advance knowledge on where to place electrodes is needed so as not to miss the seizure onset zone. Yet even with this complex process, the outcome is that ~40-50% of patients continue with significant seizures. While studies using MR spectroscopic imaging (MRSI) have shown it to be sensitive to regions of brain dysfunction, its utility has been limited by technical problems that restrict the breadth of brain coverage and the accuracy of the measurement. Thus we believe that each of our proposed MR developments have an immediate and practical impact on how well we can assess neocortical epilepsy and is therefore a good match between development and implementation. Finally, while the distinctive approaches taken in this project are geared for 7T MRSI, it is also clear that our developments have substantial backwards insight for lower field as well. Specifically, even at 3T, there have been problems with field homogeneity well acknowledged by expert practitioners-some of which can be substantially overcome with our 7T developments. Thus we anticipate this project will have wide impact, for 3T, 7T imaging and for neocortical epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB011639-02
Application #
8249832
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Liu, Guoying
Project Start
2011-05-01
Project End
2015-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$504,652
Indirect Cost
$186,561
Name
Yale University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hetherington, Hoby P; Hamid, Hamada; Kulas, Joseph et al. (2014) MRSI of the medial temporal lobe at 7 T in explosive blast mild traumatic brain injury. Magn Reson Med 71:1358-67
Pan, J W; Duckrow, R B; Spencer, D D et al. (2013) Selective homonuclear polarization transfer for spectroscopic imaging of GABA at 7T. Magn Reson Med 69:310-6
Pan, Jullie W; Duckrow, Robert B; Gerrard, Jason et al. (2013) 7T MR spectroscopic imaging in the localization of surgical epilepsy. Epilepsia 54:1668-78
Avdievich, Nikolai I; Pan, Jullie W; Hetherington, Hoby P (2013) Resonant inductive decoupling (RID) for transceiver arrays to compensate for both reactive and resistive components of the mutual impedance. NMR Biomed 26:1547-54