Direct Detection of Neural Magnetic Fields with Fast-Temporal Resolution Magnetic Resonance Spectroscopy Pubblico

Abstract

Functional magnetic resonance imaging (fMRI) indirectly detects brain activation by measuring the hemodynamic response to increased energy demand. The detection of neural magnetic fields (NMFs) with MRI seeks to improve the temporal and spatial accuracy of fMRI by directly measuring the electrical responses of the brain. In vivo studies of the human brain provide conflicting results for the true detection of NMFs and are hypothesized to be contaminated by signal changes originating from the blood. Our experiments are the first to measure axonal NMFs by examining the free-induction decay (FID) at a sub-millisecond temporal resolution. Two in vitro preparations were chosen to eliminate confounding signal changes attributed to the vasculature and simultaneous field potential recording was used to time-lock neural activity to the onset of the FID. In the first study, we experimentally measured an FID phase change associated with a single evoked action potential from the earthworm giant axon system. A maximum phase change of [-1.2 ± 0.3] x 10^-5 radians was observed in the background-subtracted FID. In addition, the experimental phase time course correlated well with a theoretical phase time course in both amplitude and temporal characteristics. In this way, this study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using magnetic resonance technology. In the second study, we determined that the signal changes associated with evoked CA1 neurons of the rat hippocampal slice were 25 to 100 times below our detection limits. Theoretical simulations and experimental measurements support that our methods are sensitive to axonal components of the evoked NMF and insensitive to dendritic components. In this way, our technique measures signal changes originating from the white matter, unlike current fMRI techniques that measure signal changes originating from the gray matter.

Table of Contents

CHAPTER 1: General Introduction

1-1 Introduction....................................................................................................... 2

1-2 Magnetic Resonance Spectroscopy (MRS) Physics and

Theory of Neural Magnetic Field (NMF) Detection............................................................ 3

1-3 Magnetoencephalography..................................................................................... 5

1-4 Phantom Models.................................................................................................. 6

1-5 Computer Modeling.............................................................................................. 7

1-6 Human Studies.................................................................................................... 9

1-7 In Vitro Studies................................................................................................. 11

1-8 Summary.......................................................................................................... 12

CHAPTER 2: The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

2-1 Abstract........................................................................................................... 15 2-2 Introduction...................................................................................................... 16 2-3 Materials and Methods......................................................................................... 21

2-3.1 Earthworm Nerve Cord Preparation...................................................................... 21

2-3.2 Chamber Allowing Simultaneous Field Potential

Recordings and MRS................................................................................................. 21

2-3.3 Data Acquisition - Electrophysiology.................................................................... 22

2-3.4 Data Acquisition - MRS..................................................................................... 23

2-3.5 Data Analysis - Electrophysiology....................................................................... 24

2-3.6 Data Analysis - MRS........................................................................................ 24

2-3.7 Correction of Action Potential Timing Based on

Conduction Velocity................................................................................................. 25

2-3.8 Modeled Magnetic Resonance (MR) Magnitude and

Phase Change........................................................................................................ 26 2-4 Results............................................................................................................ 31

2-4.1 Measuring an Evoked Action Potential with

Simultaneous Electrophysiology and MRS..................................................................... 31

2-4.2 Theoretical MR Magnitude and Phase Change....................................................... 31

2-4.3 Correlation of Theory and Experiment................................................................. 32

2-2.4 Individual Worm Analysis.................................................................................. 32

2-5 Discussion....................................................................................................... 39

2-5.1 Technical Considerations................................................................................. 39

2-5.2 Phase Difference............................................................................................ 41

2-5.3 Volume Conductor Model.................................................................................. 42

2-5.4 Symmetrical vs. Asymmetrical Distribution of the NMF............................................ 43

2-5.5 Physiology of the Phase Change........................................................................ 44

2-5.6 Lorentz Effect Imaging.................................................................................... 46

2-5.7 Extrapolation to In Vivo Studies and Application................................................... 47 2-6 Conclusion....................................................................................................... 48

CHAPTER 3: Examining the Direct Detection of Evoked Potentials in the CA1 Region of the Rat Hippocampus with Magnetic Resonance Spectroscopy

3-1 Abstract......................................................................................................... 50 3-2 Introduction.................................................................................................... 51 3-3 Materials and Methods...................................................................................... 54

3-3.1 Rat Brain Isolation and Preparation.................................................................... 54

3-3.2 Hippocampal Slice Preparation.......................................................................... 55

3-3.3 Electrodes and Electrophysiological Equipment.................................................... 56

3-3.4 Field Recordings of Spontaneous CA1 Activity..................................................... 56

3-3.5 Field Recordings of Evoked CA1 Activity............................................................. 57

3-3.6 Manufacture of Radio-Frequency (RF) Microcoils and

Circuit Boards....................................................................................................... 58

3-3.7 Chamber Allowing Simultaneous Field Potential

Recordings and MRS.............................................................................................. 60

3-3.8 Tuning, Matching and Quality Factor of the Microcoil........................................... 62

3-3.9 Calculating B0 Phase Difference Maps............................................................... 62

3-3.10 Calculating the Microcoil Signal-to-Noise Ratio (SNR)

and Signal Decay Time (T2*).................................................................................. 63

3-3.11 Determining the Microcoil Excitation Power...................................................... 64

3-3.12 Simultaneous Field Recording Acquisition......................................................... 65

3-3.13 Simultaneous MRS Acquisition....................................................................... 67

3-3.14 Data Analysis - Simultaneous Electrophysiology................................................ 68

3-3.15 Data Analysis - Simultaneous MRS................................................................. 68

3-3.16 Modeled MR Magnitude and Phase Change....................................................... 68

3-4 Results......................................................................................................... 76

3-4.1 Preliminary Field Potential Recordings............................................................... 76

3-4.2 Phase Difference Maps.................................................................................. 76

3-4.3 Free-Induction Decay (FID) SNR and T2*......................................................... 77

3-4.4 Microcoil Excitation Power............................................................................. 78

3-4.5 Simultaneous Field Potential Recordings and MRS

in the Hippocampal Slice....................................................................................... 78

3-5 Discussion.................................................................................................... 87

3-5.1 Silicon vs. Glass Microcoil Substrate............................................................... 87

3-5.2 Determination of the Excitation Power............................................................. 89

3-5.3 Simultaneous Field Potential Recordings and MRS

Following Evoked Activity in CA1............................................................................ 91

3-5.4 Simulated Effects of Evoked CA1 Hippocampal Neuron

Activity on the MR Signal...................................................................................... 93

3-5.5 Comparing the Simultaneous Hippocampal Experiment

to the Simulation in CA1 Pyramidal Neurons.............................................................. 96

3-5.6 Inability to Detect Hippocampal NMFs and

Future Directions................................................................................................ 97 3-6 Conclusion.................................................................................................. 100

CHAPTER 4: Conclusions and Future Directions

4-1 Conclusions................................................................................................. 102 4-2 Future Directions.......................................................................................... 104

REFERENCES ................................................................................................... 108

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Neuroscience
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Biology, Neuroscience
Parola chiave	Neural Magnetic Fields Action Potential Magnetic Resonance Spectroscopy Local Field Potentials Earthworm Hippocampal Slice Free Induction Decay
Committee Chair / Thesis Advisor	Hu, Xiaoping P, Emory University
Committee Members	Sathian, Krish, Emory University James, George Andrew, Emory University Keilholz, Shella D, Emory University Dingledine, Raymond J, Emory University

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