Keywords: Small Animals, Brain, TMS, CBV, basal metabolism

Motivation: Transcranial magnetic stimulation (TMS) shows promise as a therapeutic intervention for many neuropsychiatric conditions. Yet, pinpointing the appropriate stimulation target remains elusive.

Goal(s): To identify brain regions affected by prolonged cocaine exposure, and to identify potential targets for focal TMS.

Approach:  Basal CBV were mapped by injecting iron-oxide contrast. Multi-echo gradient echo and spin echo sequences were employed to generate maps of 05732972-a323-4027-8676-ccee7744913e">R2. 

Results: Many brain regions, including the prelimbic cortex, exhibited a significant decrease in basal CBV following prolonged cocaine exposure. The prelimbic cortex is situated relatively close to the cortical surface and presents a promising candidate for TMS.

Impact: Likely the first attempt to identify TMS targets using the CBV mapping approach.

Keywords: Biology, Models, Methods, Multiple Sclerosis, blood brain barrier permeability

Motivation: Blood brain barrier (BBB) dysregulation is one of the earliest signs of multiple sclerosis (MS) and the mechanism underlying BBB breakdown is not completely understood. 

Goal(s): We sought to use the non-obese diabetic experimental allergic encephalomyelitis (NOD-EAE) mouse model of secondary progressive MS to understand BBB breakdown in efforts to explore potential MS therapeutics.

Approach: MRI was used to quantify BBB permeability metrics using gadolinium contrast agent. 

Results: We quantified the spatial and temporal characterization of BBB permeability in NOD-EAE mice with progressing disease using MRI. These quantifying parameters can potentially be used to test the effect of therapeutic agents on BBB breakdown.

Impact: The NOD-EAE mouse model of secondary progressive multiple sclerosis (SPMS) can potentially be used to assess blood brain barrier characteristics using contrast-enhanced MRI in efforts to test therapeutic agents that can be used in the treatment of SPMS. 

Keywords: Neurofluids, Neurofluids

Motivation: This research aims to explore the relationship between CSF dynamics and BOLD signals using EPI-based resting-state fMRI data from an open database of rat models.

Goal(s):  Rodents and humans are compared regarding CSF dynamics and the BOLD signal.
 

Approach: The study computes temporal correlations between CSF pulse, CSF edge, and the BOLD signal.
 

Results:  While in resting state, both CSFpulse and CSFedge indices were correlated with global BOLD, exhibiting a stronger correlation for CSFedge and varying peak correlations at -1s, -10s, and +11s. The temporal correlation between CSF dynamics and global BOLD indicates differences in CSF physiology in humans compared to smaller animals.

Impact: The study results imply differing correlation coefficients between CSF dynamics and the BOLD signal, suggesting promising pathways for deeper investigations into brain CSF dynamics in small animal models and neuroscientific advancements using EPI-based fMRI database.   

Keywords: Preclinical Image Analysis, Preclinical, Amyotrophic lateral sclerosis (ALS)

Motivation: Amyotrophic lateral sclerosis is still an understudied disease, and early detection is important.

Goal(s): This study aimed to clarify the transition of the pathophysiology and evaluate the relationship between the abnormalities detected on magnetic resonance imaging and the development of clinical symptoms by combining the T₂ map data obtained in the previous study with behavioral analysis.

Approach: Behavioral analysis was performed on four parameters, namely, bodyweight, general condition, hind-foot reflex test, and landing foot-splay test. Correlation analysis of the behavioral analysis data and T₂ map data was performed in each voxel. 

Results: A correlation was detected in the trigeminal motor nucleus.

Impact: Changes in the trigeminal motor nucleus are indicated to be closely related to early changes in amyotrophic lateral sclerosis (ALS). This finding is suggested to be useful for the early diagnosis of ALS in humans and research on novel treatments.

Keywords: Small Animals, Relaxometry

Motivation: Measuring T2* in mouse brains may therefore be of interest in assessing pathological models or innovative treatments directed against these pathologies.

Goal(s): The goal of this study was to obtain a high resolution and accurate T2* map of the mouse brain ex vivo and in vivo.

Approach: A 3D Multi Gradient Echo sequence with a drift compensation module was used and combined with an optimized fitting model which takes account the non-central chi distribution of the multi-channel gaussian noise.

Results: T2* map were obtained ex vivo and in vivo at 117 µm isotropic resolution in 20 minutes.

Impact: A high-resolution 3D Multi-Gradient Echo sequence sequence has been coupled with an optimized fitting algorithm to generate high resolution T2* map of the mouse brain. This method can be used to study preclinical stroke model.

Keywords: Biomarkers, Traumatic brain injury

Motivation: Imaging biomarkers accurately diagnosing and monitoring treatment response for chronic mild Traumatic Brain Injury (mTBI) are needed. 

Goal(s): This study aimed to experimentally validate and determine the performance of MRI biomarkers for monitoring chronic repetitive mild traumatic brain injury (mTBI). 

Approach: We used diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) to assess white matter injury in mouse brains with chronic mTBI and compared results with those for age-matched control brains. 

Results: Reduction in fractional anisotropy and increase of axial kurtosis were observed in the medulla of mTBI brains compared to the parameters in the same region of control brains.

Impact: It is new to monitor DTI and DKI parameters as noninvasive biomarkers in the brain with chronic mTBI.

Keywords: Preclinical Image Analysis, Brain Connectivity, axial diffusivity, marmosets, brain volume

Motivation: A direct examining the volume and diffusion indices of in vivo and ex vivo brains from the same individual is of great interest in linking clinical and histological studies.

Goal(s): The goal of this study is to investigate the relationship between brain volume and diffusion indices in brain using in vivo and ex vivo brains from the same individual.

Approach: Dwi indices and brain volumes of the whole brain, white matter, cerebral cortex, cerebellum, and 52 brain regions were compared in vivo and ex vivo from same individuals.

Results: For each DWI index, AD was correlated with volume change in 40 cortical regions.

Impact: This study successfully compared the same brain in vivo and ex vivo directly, and it sufficiently demonstrates the relationship between volume and diffusion indices. In particular, AD is most sensitive to regional volume changes.

Keywords: Small Animals, CEST & MT, Drugs, metabolites, antiretroviral, HIV, ART, gluatamate, creatine

Motivation: The neurotoxicity of antiretroviral (ARV) drugs has been reported to affect neurocognition.

Goal(s): In this study, we tried to link CEST results of ARVs and metabolites to elucidate the effects of ARVs on metabolic alterations.

Approach: Mice administrated with TDF/3TC/DTG were scanned using CEST MRI to detect 3TC (at 1 and 2 ppm) and TDF (at 3 ppm). Metabolites were also measured using CEST MRI.

Results: Results showed that when used in combination, MRI is not sensitive to the CEST contrasts of 3TC and TDF. Glutamate, creatine and NOE were affected by TLD indicating the toxicity of TLD.

Impact: The study showed the potential to use CEST MRI to elucidate the effects of antiretroviral drugs on the neuropathologic outcomes by testing the association of MRI measurements of ARVs and metabolic imaging results.

Keywords: Preclinical Image Analysis, Data Acquisition, Flow measurment

Motivation: Non-invasive measurement of intracranial flow can elucidate fluid interactions within the brain. However, it's essential to determine the range of velocities that can be reliably measured using this approach.

Goal(s): Our aim is to assess the ability of PC MRI "Flow Compensated Fast low angle Shot (fcFLASH)" based sequence for velocity measurements in small blood vessels and cerebrospinal fluid in rats.

Approach: A phantom is built to simulate fluid flow. Measurements are repeated for each velocity range.

Results: Non gated fcFLASH-based PC MRI allows a rough estimation of flow velocities on the order of 0.5 cm/s.

Impact: our study shows that the fcFLASH-based PC MRI can be used for a rough estimation of a small fluid circulation. A methodological development is necessary for a reliable measurement.