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Image-guided pulsed focused ultrasound (pFUS) is a non-invasive technique that can increase tropism of intravenously (IV)-infused mesenchymal stromal cells (MSC) to sonicated tissues. MSC have shown promise for cardiac regenerative medicine strategies but can be hampered by inefficient homing to the myocardium. This study sonicated the left ventricles (LV) in rats with magnetic resonance imaging (MRI)-guided pFUS and examined both proteomic responses and subsequent MSC tropism to treated myocardium. T2-weighted MRI was used for pFUS targeting of the entire LV. pFUS increased numerous pro- and anti-inflammatory cytokines, chemokines, and trophic factors and cell adhesion molecules in the myocardial microenvironment for up to 48 hours post-sonication. Cardiac troponin I and N-terminal pro-B-type natriuretic peptide were elevated in the serum and myocardium. Immunohistochemistry revealed transient hypoxia and immune cell infiltration in pFUS-targeted regions. Myocardial tropism of IV-infused human MSC following pFUS increased twofold-threefold compared with controls. Proteomic and histological changes in myocardium following pFUS suggested a reversible inflammatory and hypoxic response leading to increased tropism of MSC. MR-guided pFUS could represent a non-invasive modality to improve MSC therapies for cardiac regenerative medicine approaches., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Metabolic abnormalities are commonly observed in traumatic brain injury (TBI) patients exhibiting long-term neurological deficits. This study investigated the feasibility and reproducibility of using chemical exchange saturation transfer (CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the selective saturation for enhancing the endogenous contrast-weighting of the proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in the resting rat brain. The optimized glucoCEST-weighted imaging was performed on a closed-head model of diffuse TBI in rats with 2-deoxy-D-[ 14 C]-glucose (2DG) autoradiography validation. The results demonstrated that saturation duration of 1‒2 seconds at pulse powers 1.5‒2µT resulted in an improved contrast-to-noise ratio between the gray and white matter comparable to 2DG autoradiographs. The intrasubject (n = 4) and intersubject (n = 3) coefficient of variations for repeated glucoCEST acquisitions (n = 4) ranged between 8‒16%. Optimization for the TBI study revealed that glucoCEST-weighted images with 1.5μT power and 1 s saturation duration revealed the greatest changes in contrast before and after TBI, and positively correlated with 2DG autoradiograph (r = 0.78, p < 0.01, n = 6) observations. These results demonstrate that glucoCEST-weighted imaging may be useful in detecting metabolic abnormalities following TBI.

Background: Image-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues. However, molecular changes in the myocardium after sonication have not been widely investigated. Magnetic-resonance (MR)-guided pulsed focused ultrasound (pFUS) was targeted to the rat myocardium over a range of pressures and the microenvironmental and histological effects were evaluated over time., Methods: Eight-to-ten-week-old Sprague-Dawley rats received T2-weighted MR images to target pFUS to the left ventricular and septum without cardiac or respiratory gating. Rats were sonicated through the thoracic wall at peak negative pressures (PNP) from 1 to 8 MPa at a center frequency of 1 MHz, 10 ms pulse duration and 1 Hz pulse repetition frequency for 100 pulses per focal target. Following pFUS, myocardium was harvested over 24 h and subjected to imaging, proteomic, and histological measurements., Results: pFUS to the myocardium increased expression of cytokines, chemokines, and trophic factors characterized by an initial increase in tumor necrosis factor (TNF)-α followed by increases in pro- and anti-inflammatory factors that returned to baseline by 24 h. Immediately after pFUS, there was a transient (< 1 h) increase in N-terminal pro b-type natriuretic peptide (NT-proBNP) without elevation of other cardiac injury markers. A relationship between PNP and expression of TNF-α and NT-proBNP was observed with significant changes (p < 0.05 ANOVA) ≥ 4 MPa compared to untreated controls. Contrast-enhanced ex vivo T1-weighted MRI revealed vascular leakage in sonicated myocardium that was accompanied by the presence of albumin upon immunohistochemistry. Histology revealed infiltration of neutrophils and macrophages without morphological myofibril changes in sonicated tissue accompanied by pulmonary hemorrhage at PNP > 4 MPa., Conclusions: MR-guided pFUS to myocardium induced transient proteomic and histological changes. The temporal proteomic changes in the myocardium indicate a short-lived sterile inflammatory response consistent with ischemia or contusion. Further study of myocardial function and strain is needed to determine if pFUS could be developed as an experimental model of cardiac injury and chest trauma.

Objective: Metrics of diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) can detect diffuse axonal injury in traumatic brain injury (TBI). The relationship between the changes in these imaging measures and the underlying pathologies is still relatively unknown. This study investigated the radiological-pathological correlation between these imaging techniques and immunohistochemistry using a closed head rat model of TBI., Methods: TBI was performed on female rats followed longitudinally by magnetic resonance imaging (MRI) out to 30 days postinjury, with a subset of animals selected for histopathological analyses. A MRI-based finite element analysis was generated to characterize the pattern of the mechanical insult and estimate the extent of brain injury to direct the pathological correlation with imaging findings., Results: DTI axial diffusivity and fractional anisotropy (FA) were sensitive to axonal integrity, whereas radial diffusivity showed significant correlation to the myelin compactness. FA was correlated with astrogliosis in the gray matter, whereas mean diffusivity was correlated with increased cellularity. Secondary inflammatory responses also partly affected the changes of these DTI metrics. The magnetization transfer ratio (MTR) at 3.5ppm demonstrated a strong correlation with both axon and myelin integrity. Decrease in MTR at 20ppm correlated with the extent of astrogliosis in both gray and white matter., Interpretation: Although conventional T2-weighted MRI did not detect abnormalities following TBI, DTI and MTI afforded complementary insight into the underlying pathologies reflecting varying injury states over time, and thus may substitute for histology to reveal diffusive axonal injury pathologies in vivo. This correlation of MRI and histology furthers understanding of the microscopic pathology underlying DTI and MTI changes in TBI. Ann Neurol 2016;79:907-920., (© 2016 American Neurological Association.)

The olive baboon (Papio anubis) is phylogenetically proximal to humans. Investigation into the baboon brain has shed light on the function and organization of the human brain, as well as on the mechanistic insights of neurological disorders such as Alzheimer's and Parkinson's. Non-invasive brain imaging, including positron emission tomography (PET) and magnetic resonance imaging (MRI), are the primary outcome measures frequently used in baboon studies. PET functional imaging has long been used to study cerebral metabolic processes, though it lacks clear and reliable anatomical information. In contrast, MRI provides a clear definition of soft tissue with high resolution and contrast to distinguish brain pathology and anatomy, but lacks specific markers of neuroreceptors and/or neurometabolites. There is a need to create a brain atlas that combines the anatomical and functional/neurochemical data independently available from MRI and PET. For this purpose, a three-dimensional atlas of the olive baboon brain was developed to enable multimodal imaging analysis. The atlas was created on a population-representative template encompassing 89 baboon brains. The atlas defines 24 brain regions, including the thalamus, cerebral cortex, putamen, corpus callosum, and insula. The atlas was evaluated with four MRI images and 20 PET images employing the radiotracers for [11C]benzamide, [11C]metergoline, [18F]FAHA, and [11C]rolipram, with and without structural aids like [18F]flurodeoxyglycose images. The atlas-based analysis pipeline includes automated segmentation, registration, quantification of region volume, the volume of distribution, and standardized uptake value. Results showed that, in comparison to PET analysis utilizing the "gold standard" manual quantification by neuroscientists, the performance of the atlas-based analysis was at >80 and >70% agreement for MRI and PET, respectively. The atlas can serve as a foundation for further refinement, and incorporation into a high-throughput workflow of baboon PET and MRI data. The new atlas is freely available on the Figshare online repository (https://doi.org/10.6084/m9.figshare.16663339), and the template images are available from neuroImaging tools & resources collaboratory (NITRC) (https://www.nitrc.org/projects/haiko89/). [ABSTRACT FROM AUTHOR]

Multiple sclerosis is characterized by inflammatory demyelination and irreversible axonal injury leading to permanent neurological disabilities. Diffusion tensor imaging demonstrates an improved capability over standard magnetic resonance imaging to differentiate axon from myelin pathologies. However, the increased cellularity and vasogenic oedema associated with inflammation cannot be detected or separated from axon/myelin injury by diffusion tensor imaging, limiting its clinical applications. A novel diffusion basis spectrum imaging, capable of characterizing water diffusion properties associated with axon/myelin injury and inflammation, was developed to quantitatively reveal white matter pathologies in central nervous system disorders. Tissue phantoms made of normal fixed mouse trigeminal nerves juxtaposed with and without gel were employed to demonstrate the feasibility of diffusion basis spectrum imaging to quantify baseline cellularity in the absence and presence of vasogenic oedema. Following the phantom studies, in vivo diffusion basis spectrum imaging and diffusion tensor imaging with immunohistochemistry validation were performed on the corpus callosum of cuprizone treated mice. Results demonstrate that in vivo diffusion basis spectrum imaging can effectively separate the confounding effects of increased cellularity and/or grey matter contamination, allowing successful detection of immunohistochemistry confirmed axonal injury and/or demyelination in middle and rostral corpus callosum that were missed by diffusion tensor imaging. In addition, diffusion basis spectrum imaging-derived cellularity strongly correlated with numbers of cell nuclei determined using immunohistochemistry. Our findings suggest that diffusion basis spectrum imaging has great potential to provide non-invasive biomarkers for neuroinflammation, axonal injury and demyelination coexisting in multiple sclerosis. [ABSTRACT FROM PUBLISHER]