It is important to note that this excitation pulse is applied at the Larmor frequency in order for the net magnetization to be perturbed in the presence of the relatively large B0 field. The brain's field of view (FOV) in the x and y directions is equal to the k-space sampling rates (∆𝑘) in the x and y directions, respectively.
Pulse sequences
The initial 90-degree excitation pulse is followed by a refocusing pulse, usually at a flip angle of 180 degrees, which allows refocusing of the transverse magnetization. As described, the SE pulse sequence is more robust to field inhomogeneities and susceptibility effects than the GRE sequence.
Basic principles of functional MRI (fMRI)
- High field fMRI
- Resting-state functional connectivity
- Pre-processing of resting-state fMRI data
- Validation of fMRI with electrophysiology
One of the first steps to fMRI preprocessing involves slice time correction (Calhoun et al., 2000). On the other hand, neuronal spiking was also found to be associated with BOLD signals (Shmuel et al., 2002; Shmuel and Leopold, 2008).
Quantitative imaging of the spinal cord
- Neuroanatomy of the spinal cord
- Functional importance of the spinal cord
- DTI in the spinal cord
- QMT in the spinal cord
- FMRI in the spinal cord
- Challenges in imaging of the spinal cord
White matter in the spinal cord forms bundles arranged in columns (dorsal, lateral and ventral), which are further divided into lanes (ascending and descending). The movement of the spinal cord is further aggravated with periodic movement of the heart and lungs.
Specific aims
Aim 1
Finally, the deleterious effects of physiological noise on spinal cord MR signals cannot be overlooked. The spinal cord is surrounded by a layer of CSF, which flows in a rostral-caudal direction each time the heart beats.
Aim 2
This pulsatile CSF flow also causes the spinal cord to move within the spinal canal, although its displacements have been shown to decrease with increasing distance from the head ( Figley and Stroman, 2007 ). The goal of this objective is to a) determine the quality of BOLD images of the rat cervical spinal cord at 9.4T, b) detect intrinsic functional connectivity patterns using an ROI-based approach, and c) quantitatively evaluate functional connectivity between the horns of the spinal cord of normal animals.
Aim 3
Appendix
Appendix A: torque and magnetic moment
In addition, the current flow and direction of rotation point to the same direction which implies that the magnetic moment and angular momentum are related by a scalar factor. This scalar factor is the gyromagnetic ratio, 𝝁 = 𝛾𝑱, and can be substituted into Equation 18 to derive Equation 2 on page 3.
Appendix B: diffusion tensor model
Instead, the diffusion tensor can be calculated with diffusion-encoded data collected from six or more directions. With the diffusion tensor calculated, three main eigenvectors can be derived by diagonalizing the matrix.
Appendix C: qMT Henkelman-Ramani’s model
Organization of the intrinsic functional network in the cervical spinal cord: A resting-state functional MRI study. Quantitative magnetization transfer characteristics of the human cervical spinal cord in vivo: application to adrenomyeloneuropathy.
VALIDATION OF SPINAL CORD FMRI WITH LFP AND SPIKE ACTIVITY IN NON-HUMAN PRIMATES ACTIVITY IN NON-HUMAN PRIMATES
Abstract
Introduction
This can be attributed to difficulties encountered in imaging the spinal cord – small physical size, pronounced physiological noise, and increased effects from susceptibility gradients (Eippert et al., 2016a). Given the complex neurovascular coupling of BOLD fMRI signals, validation of their relevance by comparisons with direct measurements of neural activity is still critical to allow more precise interpretations of BOLD fMRI findings in the spinal cord. However, direct comparisons of spontaneous electrophysiological activity and rsfMRI signals remain relatively unexplored in the brain (Huttunen et al., 2008; Scholvinck et al., 2010; Shi et al., 2017; Wilson et al., 2016) and even less is known at the spinal cord.
In the rat spinal cord, previous studies have described electrophysiological activities evoked by stimuli or movements (Inácio et al., 2016; Song and Martin, 2016), but no study has directly compared and correlated the rsfMRI signal with spontaneous neural activity in the spinal cord. gray matter.
Methods
- Animal Preparation
- Stimulus-driven LFP and MUA Data Analysis
- Stimulus Presentation Protocol
- Resting-state LFP Data Analysis
- ROI-selection of Intermediate GM
- Comparable tactile stimulus evoked responses between fMRI and electrophysiology (LFP and spike activity)
- Local spatial resting state correlation profile of the dorsal horn
- Validation of resting-state fMRI functional connectivity of the spinal horns
This was done for the left and right sides of the spinal cord for each monkey. In one of the monkeys (SM-Gua), an electrolytic lesion was created by passing a current (10 µA) through an electrode at one of the recording sites in the spinal cord (Figure 12C). Small ROIs were drawn from the dorsal to the ventral horn on one side of the spinal cord (Figure 16A).
Yellow circles present intermediate gray matter in the spinal cord used as controls for later quantifications.
Discussion and conclusions
- Agreement of electrophysiology findings with spinal rsfMRI studies
- Stimulus-evoked activations and their functional relevance
- Spinal cord of non-human primates
- Challenges of imaging and electrophysiological recordings in the spinal cord and limitations
- Conclusions
- Acknowledgements
As described in previous publications (Eippert et al., 2016a), imaging the cervical spinal cord poses several challenges. Confirmation of resting state BOLD fluctuations in the human brainstem and spinal cord after identification and removal of physiological noise. Spinal cord direct current stimulation modulates neuronal activity differentially in the dorsal and ventral spinal cord.
Differential patterns of fMRI activation to noxious heat and tactile stimuli in the primate spinal cord.
RESTING-STATE FUNCTIONAL CONNECTIVITY IN THE RAT CERVICAL SPINAL CORD AT 9.4T CERVICAL SPINAL CORD AT 9.4T
Abstract
Introduction
A recent review by Eippert and colleagues provides an overview of data acquisition and denoising processing approaches that have proven useful for spinal cord fMRI (Eippert et al., 2016a). However, several groups have overcome the challenges of spinal fMRI and reported task-induced activations in the gray matter of the human spinal cord ( Kornelsen and Stroman, 2007 ; Stroman et al., 2012 ; Stroman and Ryner, 2001 ). Spinal cord injuries in humans have also been demonstrated to exhibit changes in fMRI-detectable activation (reviewed by Stroman et al., 2014 ).
Thus, this study reports the first evidence of resting-state networks in the rat spinal cord and verifies their detectability at high field.
Methods
- Animal Preparation
- Resting-state fMRI pre-processing
- In vivo MRI
- Data and Statistical Analyses
Due to the small size of the spinal cord, only CSF voxels that were not subject to partial volume effects were selected. A transmitter-receiver radio frequency coil with a diameter of 2 cm was centered on the C4-C7 region of the rat spinal cord in the iso-center of the magnet. This was performed for all ROI pairs involving the four horns of the spinal cord and the two adjacent white matter regions within each slice.
Finally, reproducibility and agreement of binding measures were calculated within each animal and within each slice.
Results
- Quality of BOLD images at the cervical spinal cord
- Intrinsic functional connectivity patterns of the rat spinal cord horns
- Differential functional connectivity among intraslice ROIs and reproducibility
- Functional connectivity between inter-slice horns
- Effect of frequency bandpass filtering in resting-state functional connectivity
Functional connectivity patterns between dorsal-dorsal and ventral-ventral horns were reproducible across animals in this study as shown in Figure 23. Furthermore, visual inspection of the Bland-Altman plots reveals that measures of dorsal-dorsal and ventral-ventral connectivity show less areas of boundaries, meaning better agreement between measurements than those for dorsal-ventral connections. Right) Boxplots of correlation strengths between seven ROI pairs in C4/C5 (top), C5/C6 (middle), and C6/C7 (bottom) of the spinal cord.
69% and 62% of the signal strength lies in the low frequency range (<0.1Hz) in the dorsal and ventral horns respectively.
Discussion and conclusions
- Challenges in functional imaging of the rat cervical spinal cord
- Physiological noise
- Functional relevance of resting-state connectivity in the spinal cord
- Reliability and reproducibility
- Spinal cord white matter
- Effects of bandpass filtering
- Inter-species differences
- Functional connectivity along the cervical spinal cord
- Improvements and future implications
- Acknowledgements
The segmental organization of the spinal cord allows for spatial somatotopic coding of peripheral information. Fourth, the use of a 2 cm surface coil limits our field of view of the spinal cord. Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat.
Signal changes in the rat spinal cord following formalin injection into the hindpaw: characterization by functional magnetic resonance imaging.
LONGITUDINAL ASSESSMENT OF SPINAL CORD INJURY WITH MULTIPARAMETRIC QUANTITATIVE MRI
Abstract
Introduction – DTI, qMT, FMRI
It is generally accepted that SCI causes an initial phase of primary damage, during which spinal cord tissue is lost while conduction along white matter tracts and gray matter functions are disrupted (Ju et al., 2014). Similarly, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) include broader information on microstructure including cell density, axonal density, fiber coherence, and myelination ( Vedantam et al., 2014 ). While MTR is more widely used, it is also susceptible to various non-MT effects (Henkelman et al., 1993).
Recently, resting-state fMRI appears to reveal robust connectivity between spinal horns in awake humans ( Barry et al., 2014 ) and in anesthetized animals ( Chen et al., 2015 ).
Methods
- Animal surgical procedures
- Animal Preparation
- Image Acquisition
- MRI data analyses
- Histological Staining
- Behavioral assessments
Five coronal slices were collected, with the second slice covering the posterior position of the spinal cord with the dorsal column and dorsal horn. Five transverse slices were acquired with the middle slice located at the epicenter of the injury. Curve-fitted inversion recovery profile of the rat lumbar spinal cord as a function of multiple inversion times (Ti) in a representative voxel.
Due to paralysis and dragging movement of the hind legs, Von Frey tests were performed in the animals' own home cages without a wire mesh bottom.
Results
- PSR and FA Revealed Changes at the Injury Site in the Lumbar Spinal Cord
- Longitudinal PSR changes with injury and correlations with other MR metrics
- Relationship between PSR, FA and behavioral assessments
- Quantitative changes in functional connectivity post-SCI
Likewise, (B, left) mean FA values along with (B, right) statistical comparisons were calculated from runs at different times of injury. Consistent with the PSR trend, little of the epicenter tissue with positive staining for LFB was evident at week 2 post-SCI (reduced to controls). Left) Control 24-h, week-1, and week-2 time points in the spinal cord were stained for myelin using Luxol Fast Blue.
After the introduction of the injury, changes were found above (Figure 44, green background) and under injury (Figure 44, red background) with statistical comparisons between each boxplot (Figure 45).
Discussion and conclusions
- PSR as a biomarker for demyelination
- Functional relevance of myelination
- PSR and other MRI parameters
- Spinal rsfMRI as a biomarker for pathology
- Limitations and improvements
- Acknowledgements
In patients with multiple sclerosis, functional networks in the spinal cord appear to be intact at 7T, although local changes in connectivity patterns have been observed (Conrad et al., 2018). Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression after spinal cord injury in rats. Demyelination and Schwann cell responses near injury epicenter cavities after chronic human spinal cord injury.
Human Embryonic Stem Cell-Derived Oligodendrocyte Stem Cell Transplants Remyelinate and Restore Movement After Spinal Cord Injury.
SUMMARY, SIGNIFICANCES AND FUTURE STUDIES
Summary and significances
Now that fMRI protocols have been implemented in rodents and basic functional connectivity has been established, Chapter 3 presents the basis for rsfMRI as one of the benchmarks for examining changes after a contusion injury in Chapter 4. The progression of the injury during the first two weeks in white matter tracts were monitored longitudinally with DTI and qMT, while behavioral assessments and histological myelin stains were collected in parallel. In summary, this thesis measured resting-state interregional correlations in the spinal cord of animals, validated their neuronal basis, and characterized changes in spinal cord structure and function after injury.
Recent developments have demonstrated therapeutic regeneration of the disrupted neural pathway (Thuret et al., 2006) and functional electrical stimulations supporting the recovery process (Bamford and Mushahwar, 2011).
Future studies
- Z -spectra of the spinal cord after injury
- Application of machine learning methods to spinal rsfMRI data
In a contusion spinal cord injury model presented in this thesis, an excessive post-injury release of glutamate occurs within and around the injury site (McAdoo et al., 1999). One possible explanation is that the spinal cord does not cycle through its full network of connections at rest (Eippert et al., 2017). A promising technique that has been commonly used to examine fMRI data is multi-voxel pattern analysis (Mahmoudi et al., 2012).
The contralateral input to the dorsal horn of the spinal cord in the decerebrate spinal cord.
