Keywords: Biomarkers, Neuro

Motivation: Although several myelin markers have been introduced using MRI, their ability to accurately detect myelin has been limited in sensitivity and specificity.

Goal(s): MP-MRI shows promise in improving myelin mapping, but validating its effectiveness remains a challenge. Our aim is to create a MP-MRI indicator and verify its accuracy through 3D myelin histology.

Approach: We compared myelin histology in MOBP-eGFP mouse brains, which exhibit enhanced myelination with various MRI markers in the same subjects.

Results: We observed varying degrees of correlation between MRI markers and MOBP signals in different brain regions. Employing PLSR analysis revealed that MP-MRI has potential to enhance myelin mapping.

Impact: The integration of multiple MRI markers in multiparametric MRI has the potential to improve our capacity for mapping myelin in the brain. A direct biomarker of myelin would be highly impactful for management of patients with MS and de/dysmyelinating disorders.

Keywords: Small Animals, Vessels, Glymphatic

Motivation: The perivascular space (PVS) plays a crucial role in facilitating the clearance of waste products and the exchange of cerebrospinal fluid and interstitial fluid in the central nervous system.

Goal(s): However, the limited depth penetration of current imaging methods impedes the study of glymphatic dynamics in deep brain regions.

Approach: In this study, we introduced an ultra-high-resolution dynamic contrast-enhanced MRI mapping approach based on single-vessel multi-gradient-echo methods.

Results: This technique allowed the differentiation of penetrating arterioles and venules from adjacent parenchymal tissue voxels and enabled the detection of Gd-enhanced signals coupled to PVS of penetrating arterioles in the deep cortex and hippocampus.

Impact: The study revealed significant PVS-specific Gd signal enhancements, shedding light on glymphatic function in deep brain regions. These findings advance our understanding of brain-wide glymphatic dynamics and impaired waste clearance, warranting further exploration of their clinical relevance and therapeutic applications.

Keywords: Biology, Models, Methods, Perfusion, Arterial Spin Labelling

Motivation: pCASL perfusion mapping has many potential applications in preclinical imaging, but its use is still challenging particularly in mice and at higher fields due to limited sensitivity and constraints on labelling arising from the mouse’s anatomy. 

Goal(s): Here, we set to push the spatial resolution limitations of pCASL in mice by over an order of magnitude.

Approach: For this, we leverage SNR increases provided by cryogenic coils and develop a novel experimental setup optimizing and stabilizing the positioning of the mice.

Results: We then show x11 higher spatial resolution CBF maps compared to the previous state-of-the-art and higher stability and reproducibility of findings. 

Impact: We developed a setup optimizing carotid positioning for mice, thereby enabling efficient pCASL labeling. When combined with a cryogenic coil, perfusion images of the mouse brain were enhanced x11 in spatial resolution and were highly reproducible compared to current state-of-the-art. 

Keywords: Perfusion, Vessels, vessel size index, VSI, resolution dependence

Motivation: Vessel size index (VSI) MRI of the rodent brain is measured at various in-plane resolutions, but the resolution dependence of VSI has not yet been explored.

Goal(s): Here, we investigated the differences in rat brain VSI at mostly measured in-plane resolutions of 125μm² and 250μm².

Approach: Resolution-dependent differences in VSI across brain regions were investigated in in-vivo rat experiments via a steady-state susceptibility contrast method by injection of monocrystalline iron oxide nanoparticles and validated through Monte Carlo simulations.

Results: In the white matter and hippocampus regions, the VSI was measured to be 12% larger as the resolution was lowered from 125μm² to 250μm².

Impact: Because the resolution dependence of VSI quantification varies across brain regions depending on the vascular configuration within MRI voxels, caution is required when comparing and analyzing brain VSI MRI obtained at different resolutions.

Keywords: Blood Vessels, Blood vessels

Motivation: Although the brain's vascular network plays a crucial role in supplying oxygen and glucose while removing metabolic by-products to meet the high energy demands of neural information processing, our understanding of the vascular network architecture in the primate brain remains limited.

Goal(s): To address this issue, our study aims to explore the variability of the vascular network and its relationship to underlying neuroanatomy.

Approach: We investigate brain vascularity in macaque monkeys using ferumoxytol-weighted laminar MRI.

Results: We demonstrate that vascularity exhibits 3-fold variation across brain regions, moderate variability across cortical layers, distinct translaminar clusters, and strong association with neuron and synaptic densities.

Impact: Laminar ferumoxytol-weighted MRI shows considerable potential to delineate pial vessel network, intracortical feeding arteries and draining veins and density of capillary networks. The capillary density exhibits close association with the underlying neuroanatomy.

Keywords: Blood Vessels, Vessels, Ultra-high field MRI

Motivation: Hemodynamics of the cerebral cortex are shaped by vascular architecture; however, it remains challenging to study the small intracortical vascular anatomy in vivo.

Goal(s): To test whether intracortical arterioles can be detected in vivo in non-human primates at 7 Tesla using a conventional human MRI scanner, and to study the organization of arterials and venules.

Approach: After conducting time-of-flight (TOF) contrast simulations, optimized TOF-MRA images from macaques were acquired using a 7T large-bore MRI scanner with 64-μm in-plane resolution.

Results: Intracortical arterioles and venules were reliably imaged and exhibited cortical area-specific differences in distribution. Imaging times were as fast as 10 minutes.

Impact: Using a standard human 7T MRI scanner, we illustrate that micron-scale intracortical arterioles are detectable non-invasively in vivo in primates. We suggest similar methods can be used to study human microvascular organization in health and disease.

Keywords: Large Animals, Nonhuman Primates, Susceptibility, Marmoset, Nonhuman primate, QSM, R2*, SWI, 9.4T, High-field

Motivation: Quantitative Susceptibility Mapping (QSM) is still not widely employed in non-human primates (NHP). Although it has been recently applied to cynomolgus and rhesus macaques, little attention has been given to other NHPs like marmosets. 

Goal(s): Our goal was to establish QSM in marmosets at 9.4 T. 

Approach: We conducted high-field MRI on 33 healthy marmosets to achieve superior spatial resolution and sensitivity. We evaluated the contrast-to-noise ratio in the QSM map for four subcortical structures and generated cortex intensity profiles.   

Results: In the marmoset brain, QSM provided excellent contrast of subcortical structure, various white matter tracts, and the cortex.

Impact: Establishing QSM in marmosets may be helpful to those interested in comprehending brain tissue structure and organization, refining brain parcellation, and facilitating procedures like MRI-guided stereotactic surgery, injections, and precise neuronal targeting.

Keywords: Large Animals, Nonhuman Primates, White Matter, Non-Human Primates, Modeling, Normal Development

Motivation: Non-human primates are thought to develop 3-4 times faster than humans based on sexual maturity and death; however, there has been a lack of quantitative data to support this ratio to describe brain development. 

Goal(s): Our goal was to find a quantitative relationship between the rate of white matter myelination in rhesus macaques and humans.

Approach: We compared rates of change in quantitative relaxometry MRI T1 values in six ROIs for rhesus macaques and human infants.

Results: We found a ratio ranging from 4.7 to 6.2 in the ROIs, corresponding to 4.7-6.2 times faster white matter myelination in rhesus macaques than humans.

Impact: By providing a quantitative approach to comparing early-life rhesus macaques white matter development with human infants, research that relates rhesus macaques and human brain development can make a more informed comparison, assisting researchers in translating results between species.

Keywords: Pharmacology, Translational Studies, Psychedelics; phMRI; fMRI; Pharmacology; 5-HT2AR

Motivation: Acute effects of psychedelic drugs are under-reported in neuroimaging studies, warranting further investigation of their immediate pharmacology to explore the potential to monitor treatment response with imaging.

Goal(s): Our goal was to assess acute impacts of serotonergic (psychedelic and non-psychedelic) agonists on hemodynamics in non-human primates (NHP).

Approach: Pharmacological-MRI (phMRI) was used to measure cerebral blood volume (CBV) changes by psilocybin, lisuride and 25CN-NBOH.

Results: Psilocybin and lisuride induced bi-phasic hemodynamic response, whereas 25CN-NBOH was monophasic. Bi-phasic phenomena may be due to non-selectivity of agonist drugs. Elevated CBV at higher psilocybin doses persists longitudinally, while lisuride and 25CN-NBOH modulations trend toward baseline.

Impact: Bi-phasic signal profiles and downstream impacts to cerebral hemodynamics may reflect non-selective targeting of psilocybin and lisuride, highlighting the sensitivity of phMRI in drug evaluation.