Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Receiver phase alignment using fitted SVD derived sensitivities from routine prescans.

Magnetic resonance imaging radio frequency arrays are composed of multiple receive coils that have their signals combined to form an image. Combination requires an estimate of the radio frequency coil sensitivities to align signal phases and prevent destructive interference. At lower fields this can be accomplished using a uniform physical reference coil. However, at higher fields, uniform volume coils are lacking and, when available, suffer from regions of low receive sensitivity that result in poor sensitivity estimation and combination. Several approaches exist that do not require a physical reference coil but require manual intervention, specific prescans, or must be completed post-acquisition. This makes these methods impractical for large multi-volume datasets such as those collected for novel types of functional MRI or quantitative susceptibility mapping, where magnitude and phase are important. This pilot study proposes a fitted SVD method which utilizes existing combination methods to create a phase sensitive combination method targeted at large multi-volume datasets. This method uses any multi-image prescan to calculate the relative receive sensitivities using voxel-wise singular value decomposition. These relative sensitivities are fitted to the solid harmonics using an iterative least squares fitting algorithm. Fits of the relative sensitivities are used to align the phases of the receive coils and improve combination in subsequent acquisitions during the imaging session. This method is compared against existing approaches in the human brain at 7 Tesla by examining the combined data for the presence of singularities and changes in phase signal-to-noise ratio. Two additional applications of the method are also explored, using the fitted SVD method in an asymmetrical coil and in a case with subject motion. The fitted SVD method produces singularity-free images and recovers between 95-100% of the phase signal-to-noise ratio depending on the prescan data resolution. Using solid harmonic fitting to interpolate singular value decomposition derived receive sensitivities from existing prescans allows the fitted SVD method to be used on all acquisitions within a session without increasing exam duration. Our fitted SVD method is able to combine imaging datasets accurately without supervision during online reconstruction.

Effects of phase regression on high-resolution functional MRI of the primary visual cortex.

High-resolution functional MRI studies have become a powerful tool to non-invasively probe the sub-millimeter functional organization of the human cortex. Advances in MR hardware, imaging techniques and sophisticated post-processing methods have allowed high resolution fMRI to be used in both the clinical and academic neurosciences. However, consensus within the community regarding the use of gradient echo (GE) or spin echo (SE) based acquisition remains largely divided. On one hand, GE provides a high temporal signal-to-noise ratio (tSNR) technique sensitive to both the macro- and micro-vascular signal while SE based methods are more specific to microvasculature but suffer from lower tSNR and specific absorption rate limitations, especially at high field and with short repetition times. Fortunately, the phase of the GE-EPI signal is sensitive to vessel size and this provides a potential avenue to reduce the macrovascular weighting of the signal (phase regression, Menon 2002). In order to determine the efficacy of this technique at high-resolution, phase regression was applied to GE-EPI timeseries and compared to SE-EPI to determine if GE-EPI's specificity to the microvascular compartment improved. To do this, functional data was collected from seven subjects on a neuro-optimized 7 T system at 800 µm isotropic resolution with both GE-EPI and SE-EPI while observing an 8 Hz contrast reversing checkerboard. Phase data from the GE-EPI was used to create a microvasculature-weighted time series (GE-EPI-PR). Anatomical imaging (MP2RAGE) was also collected to allow for surface segmentation so that the functional results could be projected onto a surface. A multi-echo gradient echo sequence was collected and used to identify venous vasculature. The GE-EPI-PR surface activation maps showed a high qualitative similarity with SE-EPI and also produced laminar activity profiles similar to SE-EPI. When the GE-EPI and GE-EPI-PR distributions were compared to SE-EPI it was shown that GE-EPI-PR had similar distribution characteristics to SE-EPI (p < 0.05) across the top 60% of cortex. Furthermore, it was shown that GE-EPI-PR has a higher contrast-to-noise ratio (0.5 ± 0.2, mean ± std. dev. across layers) than SE-EPI (0.27 ± 0.07) demonstrating the technique has higher sensitivity than SE-EPI. Taken together this evidence suggests phase regression is a useful method in low SNR studies such as high-resolution fMRI.

A framework for evaluating correspondence between brain images using anatomical fiducials.

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.

Using MRI cell tracking to monitor immune cell recruitment in response to a peptide-based cancer vaccine.

PURPOSE: MRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into the mechanism of action, temporal progression of tumor growth, and individual potency of therapies. To evaluate whether MRI could be used to track immune cell populations in response to immunotherapy, CD8+ cytotoxic T cells, CD4+ CD25+ FoxP3+ regulatory T cells, and myeloid-derived suppressor cells were labeled with superparamagnetic iron oxide particles. METHODS: Superparamagnetic iron oxide-labeled cells were injected into mice (one cell type/mouse) implanted with a human papillomavirus-based cervical cancer model. Half of these mice were also vaccinated with DepoVaxTM (ImmunoVaccine, Inc., Halifax, Nova Scotia, Canada), a lipid-based vaccine platform that was developed to enhance the potency of peptide-based vaccines. RESULTS: MRI visualization of CD8+ cytotoxic T cells, regulatory T cells, and myeloid-derived suppressor cells was apparent 24 h post-injection, with hypointensities due to iron-labeled cells clearing approximately 72 h post-injection. Vaccination resulted in increased recruitment of CD8+ cytotoxic T cells, and decreased recruitment of myeloid-derived suppressor cells and regulatory T cells to the tumor. We also found that myeloid-derived suppressor cell and regulatory T cell recruitment were positively correlated with final tumor volume. CONCLUSION: This type of analysis can be used to noninvasively study changes in immune cell recruitment in individual mice over time, potentially allowing improved application and combination of immunotherapies. Magn Reson Med 80:304-316, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Impact of Aging on Proprioceptive Sensory Neurons and Intrafusal Muscle Fibers in Mice.

The impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers (IMFs) remains largely unexplored despite the central function these cells play in modulating voluntary movements. Here, we show that proprioceptive sensory neurons undergo deleterious morphological changes in middle age (11- to 13-month-old) and old (15- to 21-month-old) mice. In the extensor digitorum longus and soleus muscles of middle age and old mice, there is a significant increase in the number of Ia afferents with large swellings that fail to properly wrap around IMFs compared with young adult (2- to 4-month-old) mice. Fewer II afferents were also found in the same muscles of middle age and old mice. Although these age-related changes in peripheral nerve endings were accompanied by degeneration of proprioceptive sensory neuron cell bodies in dorsal root ganglia (DRG), the morphology and number of IMFs remained unchanged. Our analysis also revealed normal levels of neurotrophin 3 (NT3) but dysregulated expression of the tyrosine kinase receptor C (TrkC) in aged muscles and DRGs, respectively. These results show that proprioceptive sensory neurons degenerate prior to atrophy of IMFs during aging, and in the presence of the NT3/TrkC signaling axis.