The hippocampus and the insula are responsible for episodic memory formation and retrieval. Hence, visualization of the cytoarchitecture of such structures is of primary importance to understand the underpinnings of conscious experience. Magnetic Resonance Imaging (MRI) offers an opportunity to non-invasively image these crucial structures. However, current clinical MR imaging operates at the millimeter scale while these anatomical landmarks are organized into sub-millimeter structures. For instance, the hippocampus contains several layers, including the CA3-dentate network responsible for encoding events and experiences. To investigate whether memory loss is a result of injury or degradation of CA3/dentate, spatial resolution must exceed one hundred micron, isotropic, voxel size. Going from one millimeter voxels to one hundred micron voxels results in a 1000× signal loss, making the measured signal close to or even way below the precision of the receiving coils. Consequently, the signal magnitude that forms the structural images will be biased and noisy, which results in inaccurate contrast and less than optimal signal-to-noise ratio (SNR).<p> </p> In this paper, we propose a strategy to perform high spatial resolution MR imaging of the hippocampus and insula with 3T scanners that enables accurate contrast (no systematic bias) and arbitrarily high SNR. This requires the collection of additional repeated measurements of the same image and a proper averaging of the k-space data in the complex domain. This comes at the cost of additional scan time, but long single-session scan times are not practical for obvious reasons. Hence, we also develop an approach to combine k-space data from multiple sessions, which enables the total scan time to be split into arbitrarily short sessions, where the patient is allowed to move and rest in-between. For validation, we hereby illustrate our multi-session complex averaging strategy by providing high spatial resolution 3T MR visualization of the hippocampus and insula using an ex-vivo specimen, so that the number of sessions and the duration of each session are not limited by physiological motion or poor subject compliance.
Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a novel insight into the brain to facilitate our understanding of the brain connectivity and microstructure. While in-vivo DW-MRI enables imaging of living patients and longitudinal studies of brain changes, post-mortem ex-vivo DW-MRI has numerous advantages. Ex-vivo imaging benefits from greater resolution and sensitivity due to the lack of imaging time constraints; the use of tighter fitting coils; and the lack of movement artifacts. This allows characterization of normal and abnormal tissues with unprecedented resolution and sensitivity, facilitating our ability to investigate anatomical structures that are inaccessible in-vivo. This also offers the opportunity to develop today novel imaging biomarkers that will, with tomorrow’s MR technology, enable improved in-vivo assessment of the risk of disease in an individual. Post-mortem studies, however, generally rely on the fixation of specimen to inhibit tissue decay which starts as soon as tissue is deprived from its blood supply. Unfortunately, fixation of tissues substantially alters tissue diffusivity profiles. In addition, ex-vivo DW-MRI requires particular care when packaging the specimen because the presence of microscopic air bubbles gives rise to geometric and intensity image distortion. In this work, we considered the specific requirements of post-mortem imaging and designed an optimized protocol for ex-vivo whole brain DW-MRI using a human clinical 3T scanner. Human clinical 3T scanners are available to a large number of researchers and, unlike most animal scanners, have a bore diameter large enough to image a whole human brain. Our optimized protocol will facilitate widespread ex-vivo investigations of large specimen.