A novel MRI phantom to study interstitial fluid transport in the glymphatic system.

The glymphatic system is a recently discovered transport system, mediated by cerebral spinal fluid (CSF), that clears metabolic and cellular waste products in the brain. This system's function in the brain is analogous to that of the lymphatic system in the rest of the mammalian body. It is hypothesized that CSF clears harmful chemicals from the brain by flowing through interstitial spaces in the brain during sleep. While there is growing recognition of the critical role the glymphatic system plays in maintaining normal brain health and in explaining pathology, there are few noninvasive imaging methods that measure and characterize the efficacy of glymphatic transport in vivo. In this study we designed, constructed, and tested a glymphatic transport magnetic resonance imaging (MRI) flow phantom, which combines regions that mimic CSF-filled ventricles and brain interstitial space. We tested high- and low-q space diffusion MRI and diffusion tensor imaging (DTI) acquisitions to determine if they could detect, measure, and map interstitial glymphatic flows. The results suggest that, under certain flow conditions, diffusion-weighted MRI can detect the enhanced mixing that occurs during glymphatic clearance.

Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis.

Non-invasive imaging has the potential to play a crucial role in the characterization and translation of experimental animal models to investigate human brain development and disorders, especially when employed to study animal models that more accurately represent features of human neuroanatomy. The purpose of this study was to build and make available MRI and DTI templates and analysis tools for the ferret brain as the ferret is a well-suited species for pre-clinical MRI studies with folded cortical surface, relatively high white matter volume and body dimensions that allow imaging with pre-clinical MRI scanners. Four ferret brain templates were built in this study - in-vivo MRI and DTI and ex-vivo MRI and DTI - using brain images across many ferrets and region of interest (ROI) masks corresponding to established ferret neuroanatomy were generated by semi-automatic and manual segmentation. The templates and ROI masks were used to create a web-based ferret brain viewing software for browsing the MRI and DTI volumes with annotations based on the ROI masks. A second objective of this study was to provide a careful description of the imaging methods used for acquisition, processing, registration and template building and to demonstrate several voxelwise analysis methods including Jacobian analysis of morphometry differences between the female and male brain and bias-free identification of DTI abnormalities in an injured ferret brain. The templates, tools and methodological optimization presented in this study are intended to advance non-invasive imaging approaches for human-similar animal species that will enable the use of pre-clinical MRI studies for understanding and treating brain disorders.

Anisotropic phantom to calibrate high-q diffusion MRI methods.

A silicon oil-filled glass capillary array is proposed as an anisotropic diffusion MRI phantom. Together with a computational/theoretical pipeline these provide a gold standard for calibrating and validating high-q diffusion MRI experiments. The phantom was used to test high angular resolution diffusion imaging (HARDI) and double pulsed-field gradient (d-PFG) MRI acquisition schemes. MRI-based predictions of microcapillary diameter using both acquisition schemes were compared with results from optical microscopy. This phantom design can be used for quality control and quality assurance purposes and for testing and validating proposed microstructure imaging experiments and the processing pipelines used to analyze them.

Mapping average axon diameters in porcine spinal cord white matter and rat corpus callosum using d-PFG MRI.

Knowledge of microstructural features of nerve fascicles, such as their axon diameter, is crucial for understanding normal function in the central and peripheral nervous systems as well as assessing changes due to pathologies. In this study double-pulsed field gradient (d-PFG) filtered MRI was used to map the average axon diameter (AAD) in porcine spinal cord, which was then compared to AADs measured with optical microscopy of the same specimen, as a way to further validate this new MRI method. A novel 3D d-PFG acquisition scheme was used to obtain AADs in each voxel of a coronal slice of rat brain corpus callosum. AAD measurements were also acquired using optical microscopy performed on histological sections and validated using a glass capillary array phantom.

A spin echo sequence with a single-sided bipolar diffusion gradient pulse to obtain snapshot diffusion weighted images in moving media.

In vivo MRI data can be corrupted by motion. Motion artifacts are particularly troublesome in Diffusion Weighted MRI (DWI), since the MR signal attenuation due to Brownian motion can be much less than the signal loss due to dephasing from other types of complex tissue motion, which can significantly degrade the estimation of self-diffusion coefficients, diffusion tensors, etc. This paper describes a snapshot DWI sequence, which utilizes a novel single-sided bipolar diffusion sensitizing gradient pulse within a spin echo sequence. The proposed method shortens the diffusion time by applying a single refocused bipolar diffusion gradient on one side of a refocusing RF pulse, instead of a set of diffusion sensitizing gradients, separated by a refocusing RF pulse, while reducing the impact of magnetic field inhomogeneity by using a spin echo sequence. A novel MRI phantom that can exhibit a range of complex motions was designed to demonstrate the robustness of the proposed DWI sequence.

Double pulsed field gradient (double-PFG) MR imaging (MRI) as a means to measure the size of plant cells.

Measurement of diffusion in porous materials and biological tissues with the pulsed field gradient (PFG) MR techniques has proven useful in characterizing the microstructure of such specimens noninvasively. A natural extension of the traditional PFG technique comprises multiple pairs of diffusion gradients. This approach has been shown to provide the ability to characterize anisotropy at different length scales without the need to employ very strong gradients. In this work, the double-PFG imaging technique was used on a specimen involving a series of glass capillary arrays with different diameters. The experiments on the phantom demonstrated the ability to create a quantitative and accurate map of pore sizes. The same technique was subsequently employed to image a celery stalk. A diffusion tensor image (DTI) of the same specimen was instrumental in accurately delineating the regions of vascular tissue and determining the local orientation of cells. This orientation information was incorporated into a theoretical double-PFG framework and the technique was employed to estimate the cell size in the vascular bundles of the celery stalk. The findings suggest that the double-PFG MRI framework could provide important new information regarding the microstructure of many plants and other food products.

Observation of microscopic diffusion anisotropy in the spinal cord using double-pulsed gradient spin echo MRI.

A double-pulsed gradient spin echo (d-PGSE) filtered MRI sequence is proposed to detect microscopic diffusion anisotropy in heterogeneous specimen. The technique was developed, in particular, to characterize local microscopic anisotropy in specimens that are macroscopically isotropic, such as gray matter. In such samples, diffusion tensor MRI (DTI) produces an isotropic or nearly isotropic diffusion tensor despite the fact that the medium may be anisotropic at a microscopic length scale. Using d-PGSE filtered MRI, microscopic anisotropy was observed in a "gray matter" phantom consisting of randomly oriented tubes filled with water, as well as in fixed pig spinal cord, within a range of b-values that can be readily achieved on clinical and small animal MR scanners. These findings suggest a potential use for this new contrast mechanism in clinical studies and biological research applications.

Detection of microscopic anisotropy in gray matter and in a novel tissue phantom using double Pulsed Gradient Spin Echo MR.

A double Pulsed Gradient Spin Echo (d-PGSE) MR experiment was used to measure and assess the degree of local diffusion anisotropy in brain gray matter, and in a novel "gray matter" phantom that consists of randomly oriented tubes filled with water. In both samples, isotropic diffusion was observed at a macroscopic scale while anisotropic diffusion was observed at a microscopic scale, however, the nature of the resulting echo attenuation profiles were qualitatively different. Gray matter, which contains multiple cell types and fibers, exhibits a more complicated echo attenuation profile than the phantom. Since microscopic anisotropy was observed in both samples in the low q regime comparable to that achievable in clinical scanner, it may offer a new potential contrast mechanism for characterizing gray matter microstructure in medical and biological applications.