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The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR mouse line) for noninvasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss in both aged and young adult brains, accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at 1 mo postablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts (NBs) following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the middle cerebral artery occlusion model of ischemic stroke, NB migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose: Diffusion and lung morphometry imaging using hyperpolarized gases are promising tools to quantify pulmonary microstructure noninvasively in humans and in animal models. These techniques assume the motion encoded is exclusively diffusive gas displacement, but the impact of cardiac motion on measurements has never been explored. Furthermore, although diffusion morphometry has been validated against histology in humans and mice using 3He, it has never been validated in mice for 129Xe. Here, we examine the effect of cardiac motion on diffusion imaging and validate 129Xe diffusion morphometry in mice. Theory and Methods: Mice were imaged using gradient‐echo‐based diffusion imaging, and apparent diffusion‐coefficient (ADC) maps were generated with and without cardiac gating. Diffusion‐weighted images were fit to a previously developed theoretical model using Bayesian probability theory, producing morphometric parameters that were compared with conventional histology. Results: Cardiac gating had no significant impact on ADC measurements (dual‐gating: ADC = 0.020 cm2/s, single‐gating: ADC = 0.020 cm2/s; P =.38). Diffusion‐morphometry–generated maps of ADC (mean, 0.0165 ± 0.0001 cm2/s) and acinar dimensions (alveolar sleeve depth [h] = 44 µm, acinar duct radii [R] = 99 µm, mean linear intercept [Lm] = 74 µm) that agreed well with conventional histology (h = 45 µm, R = 108 µm, Lm = 63 µm). Conclusion: Cardiac motion has negligible impact on 129Xe ADC measurements in mice, arguing its impact will be similarly minimal in humans, where relative cardiac motion is reduced. Hyperpolarized 129Xe diffusion morphometry accurately and noninvasively maps the dimensions of lung microstructure, suggesting it can quantify the pulmonary microstructure in mouse models of lung disease. [ABSTRACT FROM AUTHOR]

Fast apparent transverse relaxation (short T2*) is a common obstacle when attempting to perform quantitative 1H MRI of the lungs. While T2* times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous 129Xe), T2* can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T2* of HP 129Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi‐echo radial flyback imaging sequence and use it to measure HP 129Xe T2* at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T1 relaxation outside the animal by using multiple gradient‐refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the 129Xe T2* in vivo for 10 healthy C57Bl/6 J mice and found T2* ~ 5 ms in the lung airspaces. Interestingly, T2* was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O2 content of the inhaled gas mixture. These results are discussed in the context of T2* relaxation within porous media. [ABSTRACT FROM AUTHOR]

This work demonstrates the first whole brain 'high spatial resolution' 7Li MR spectroscopy imaging in bipolar disorder subjects. The in vivo quantification is validated by a phantom containing 5 mM lithium salt using the identical radiofrequency sequence and imaging protocol. This study is the first demonstration of the 7Li distribution in the brain of bipolar disorder patients on lithium therapy using a 3D MR spectroscopy imaging approach. The results show that brain lithium level is strongly correlated with serum lithium concentration. The brain-to-serum lithium ratios for the average brain and the local maximum were 0.39 ± 0.08 ( r = 0.93) and 0.92 ± 0.16 ( r = 0.90), respectively. The lithium distribution is found to be nonuniform throughout the brain for all patients, which is somewhat unexpected and highly intriguing. This uneven distribution is more evident in subjects at a higher therapeutic serum lithium level. This finding may suggest that lithium targets specific brain tissues and/or certain enzymatic and macromolecular sites that are associated with therapeutic effect. Further investigations of bipolar disorder patients on lithium therapy using 3D 7Li MR spectroscopy imaging are warranted. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hyperpolarized (HP) xenon-129 ( 129 Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can be exploited to quantify pulmonary physiology, including ventilation, restricted diffusion (alveolar-airspace size), and gas exchange. In humans, it has been used to evaluate disease severity and progression in a variety of pulmonary disorders and is approved for clinical use in the United States and United Kingdom. Beyond its clinical applications, the ability of 129 Xe MRI to noninvasively assess pulmonary pathophysiology and provide spatially resolved information is valuable for preclinical research. Among animal models, mice are the most widely used due to the accessibility of genetically modified disease models. Here, 129 Xe MRI is promising as a minimally invasive, radiation-free, and sensitive technique to longitudinally monitor lung disease progression and therapy response (e.g., in drug discovery). This technique can extend to preclinical applications by incorporating an MRI-triggered, free-breathing apparatus or mechanical ventilator to deliver gas. Here, we describe the steps and provide checklists to ensure robust data collection and analysis, including creating a thermally polarized xenon gas phantom for quality control, optimizing polarization, animal handling (sedation, intubation, ventilation, and care for mice), and protocols for ventilation, restricted diffusion, and gas exchange data. While preclinical 129 Xe MRI can be applied in various animal models (e.g., rats, pigs, sheep), this protocol focuses on mice due to the challenges posed by their small anatomy, which are balanced by their affordability and the availability of many disease models.

The quantification of cardiac motion using cardiac magnetic resonance imaging (CMR) has shown promise as an early-stage marker for cardiovascular diseases. Despite the growing popularity of CMR-based myocardial strain calculations, measures of complete spatiotemporal strains (i.e., three-dimensional strains over the cardiac cycle) remain elusive. Complete spatiotemporal strain calculations are primarily hampered by poor spatial resolution, with the rapid motion of the cardiac wall also challenging the reproducibility of such strains. We hypothesize that a super-resolution reconstruction (SRR) framework that leverages combined image acquisitions at multiple orientations will enhance the reproducibility of complete spatiotemporal strain estimation. Two sets of CMR acquisitions were obtained for five wild-type mice, combining short-axis scans with radial and orthogonal long-axis scans. Super-resolution reconstruction, integrated with tissue classification, was performed to generate full four-dimensional (4D) images. The resulting enhanced and full 4D images enabled complete quantification of the motion in terms of 4D myocardial strains. Additionally, the effects of SRR in improving accurate strain measurements were evaluated using an in-silico heart phantom. The SRR framework revealed near isotropic spatial resolution, high structural similarity, and minimal loss of contrast, which led to overall improvements in strain accuracy. In essence, a comprehensive methodology was generated to quantify complete and reproducible myocardial deformation, aiding in the much-needed standardization of complete spatiotemporal strain calculations., Competing Interests: 7 Declaration of competing interest S. Sadayappan provides consulting and collaborative research studies to the Leducq Foundation (CUREPLAN), Red Saree Inc., Greater Cincinnati Tamil Sangam, Novo Nordisk, Pfizer, AavantiBio, AstraZeneca, MyoKardia, Merck and Amgen, but such work is unrelated to the content of this article. No other authors declare any conflicts of interest.

The brain's neuroreparative capacity after injuries such as ischemic stroke is contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here we report a mouse genetic tool (the ROSA26iDTR mouse line) for non-invasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at one-month post-ablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the MCAo model of ischemic stroke, neuroblast migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important and novel role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke., Competing Interests: Competing interests: The authors declare they have no competing interests.

Purpose: Diffusion and lung morphometry imaging using hyperpolarized gases are promising tools to quantify pulmonary microstructure noninvasively in humans and in animal models. These techniques assume the motion encoded is exclusively diffusive gas displacement, but the impact of cardiac motion on measurements has never been explored. Furthermore, although diffusion morphometry has been validated against histology in humans and mice using 3 He, it has never been validated in mice for 129 Xe. Here, we examine the effect of cardiac motion on diffusion imaging and validate 129 Xe diffusion morphometry in mice., Theory and Methods: Mice were imaged using gradient-echo-based diffusion imaging, and apparent diffusion-coefficient (ADC) maps were generated with and without cardiac gating. Diffusion-weighted images were fit to a previously developed theoretical model using Bayesian probability theory, producing morphometric parameters that were compared with conventional histology., Results: Cardiac gating had no significant impact on ADC measurements (dual-gating: ADC = 0.020 cm 2 /s, single-gating: ADC = 0.020 cm 2 /s; P = .38). Diffusion-morphometry-generated maps of ADC (mean, 0.0165 ± 0.0001 cm 2 /s) and acinar dimensions (alveolar sleeve depth [h] = 44 µm, acinar duct radii [R] = 99 µm, mean linear intercept [L m ] = 74 µm) that agreed well with conventional histology (h = 45 µm, R = 108 µm, L m = 63 µm)., Conclusion: Cardiac motion has negligible impact on 129 Xe ADC measurements in mice, arguing its impact will be similarly minimal in humans, where relative cardiac motion is reduced. Hyperpolarized 129 Xe diffusion morphometry accurately and noninvasively maps the dimensions of lung microstructure, suggesting it can quantify the pulmonary microstructure in mouse models of lung disease., (© 2020 International Society for Magnetic Resonance in Medicine.)