1,721,008 research outputs found
sj-pdf-1-jcb-10.1177_0271678X221117008 - Supplemental material for Whole-brain perfusion mapping in mice by dynamic BOLD MRI with transient hypoxia
No full textSupplemental material, sj-pdf-1-jcb-10.1177_0271678X221117008 for Whole-brain perfusion mapping in mice by dynamic BOLD MRI with transient hypoxia by DongKyu Lee, Thuy Thi Le, Geun Ho Im and Seong-Gi Kim in Journal of Cerebral Blood Flow & Metabolism</p
Whole-brain perfusion mapping in mice by dynamic BOLD MRI with transient hypoxia
No full textNon-invasive mapping of cerebral perfusion is critical for understanding neurovascular and neurodegenerative diseases. However, perfusion MRI methods cannot be easily implemented for whole-brain studies in mice because of their small size. To overcome this issue, a transient hypoxia stimulus was applied to induce a bolus of deoxyhemoglobins as an endogenous paramagnetic contrast in blood oxygenation level-dependent (BOLD) MRI. Based on stimulus-duration-dependent studies, 5 s anoxic stimulus was chosen, which induced a decrease in arterial oxygenation to 59%. Dynamic susceptibility changes were acquired with whole-brain BOLD MRI using both all-vessel-sensitive gradient-echo and microvascular-sensitive spin-echo readouts. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were quantified by modeling BOLD dynamics using a partial-volume-corrected arterial input function. In the mouse under ketamine/xylazine anesthesia, total CBF and CBV were 112.0 +/- 15.0 ml/100 g/min and 3.39 +/- 0.59 ml/100 g (n = 15 mice), respectively, whereas microvascular CBF and CBV were 85.8 +/- 6.9 ml/100 g/min and 2.23 +/- 0.27 ml/100 g (n = 7 mice), respectively. Regional total vs. microvascular perfusion metrics were highly correlated but a slight mismatch was observed in the large-vessel areas and cortical depth profiles. Overall, this non-invasive, repeatable, simple hypoxia BOLD-MRI approach is viable for perfusion mapping of rodents.11Nsciescopu
Mapping cerebral perfusion in mice under various anesthesia levels using highly sensitive BOLD MRI with transient hypoxia
No full textCerebral perfusion is critical for the early detection of neurological diseases and for effectively monitoring disease progression and treatment responses. Mouse models are widely used in brain research, often under anesthesia, which can affect vascular physiology. However, the impact of anesthesia on regional cerebral blood volume and flow in mice has not been thoroughly investigated. In this study, we have developed a whole-brain perfusion MRI approach by using a 5-second nitrogen gas stimulus under inhalational anesthetics to induce transient BOLD dynamic susceptibility contrast (DSC). This method proved to be highly sensitive, repeatable within each imaging session, and across four weekly sessions. Relative cerebral blood volumes measured by BOLD DSC agree well with those by contrast agents. Quantitative cerebral blood volume and flow metrics were successfully measured in mice under dexmedetomidine and various isoflurane doses using both total vasculature-sensitive gradient-echo and microvasculature-sensitive spin-echo BOLD MRI. Dexmedetomidine reduces cerebral perfusion, while isoflurane increases cerebral perfusion in a dose-dependent manner. © 2024 American Association for the Advancement of Science. All rights reserved.11Ysciescopu
Parvalbumin interneuron activity drives fast inhibition-induced vasoconstriction followed by slow substance P-mediated vasodilation
No full textThe role of parvalbumin (PV) interneurons in vascular control is poorly understood. Here, we investigated the hemodynamic responses elicited by optogenetic stimulation of PV interneurons using electrophysiology, functional magnetic resonance imaging (fMRI), wide-field optical imaging (OIS), and pharmacological applications. As a control, forepaw stimulation was used. Stimulation of PV interneurons in the somatosensory cortex evoked a biphasic fMRI response in the photostimulation site and negative fMRI signals in projection regions. Activation of PV neurons engaged two separable neurovascular mechanisms in the stimulation site. First, an early vasoconstrictive response caused by the PV-driven inhibition is sensitive to the brain state affected by anesthesia or wakefulness. Second, a later ultraslow vasodilation lasting a minute is closely dependent on the sum of interneuron multiunit activities, but is not due to increased metabolism, neural or vascular rebound, or increased glial activity. The ultraslow response is mediated by neuropeptide substance P (SP) released from PV neurons under anesthesia, but disappears during wakefulness, suggesting that SP signaling is important for vascular regulation during sleep. Our findings provide a comprehensive perspective about the role of PV neurons in controlling the vascular response.11Nsciescopu
Stem cell restores thalamocortical plasticity to rescue cognitive deficit in neonatal intraventricular hemorrhage
No full text© 2021 Elsevier Inc.Severe neonatal intraventricular hemorrhage (IVH) patients incur long-term neurologic deficits such as cognitive disabilities. Recently, the intraventricular transplantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (MSCs) has drawn attention as a therapeutic potential to treat severe IVH. However, its pathological synaptic mechanism is still elusive. We here demonstrated that the integration of the somatosensory input was significantly distorted by suppressing feed-forward inhibition (FFI) at the thalamocortical (TC) inputs in the barrel cortices of neonatal rats with IVH by using BOLD-fMRI signal and brain slice patch-clamp technique. This is induced by the suppression of Hebbian plasticity via an increase in tumor necrosis factor-α expression during the critical period, which can be effectively reversed by the transplantation of MSCs. Furthermore, we showed that MSC transplantation successfully rescued IVH-induced learning deficits in the sensory-guided decision-making in correlation with TC FFI in the layer 4 barrel cortex.11Nsciescopu
Miniaturized MR-compatible ultrasound system for real-time monitoring of acoustic effects in mice using high-resolution MRI
No full textVisualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics
Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance
No full textAlthough pain-related excessive fear is known to be a key factor in chronic pain disability, which involves the anterior cingulate cortex (ACC), little is known about the downstream circuits of the ACC for fear avoidance in pain processing. Using behavioral experiments and functional magnetic resonance imaging with optogenetics at 15.2 T, we demonstrate that the ACC is a part of the abnormal circuit changes in chronic pain and its downstream circuits are closely related to modulating sensorimotor integration and generating active movement rather than carrying sensory information. The projection from the ACC to the dorsolateral and lateral parts of the periaqueductal gray (dl/lPAG) especially enhances both reflexive and active avoidance behavior toward pain. Collectively, our results indicate that increased signals from the ACC to the dl/lPAG might be critical for excessive fear avoidance in chronic pain disability. © 2022 Elsevier Inc.11Nsciescopu
Whole-brain mapping of effective connectivity by fMRI with cortex-wide patterned optogenetics
No full textFunctional magnetic resonance imaging (fMRI) with optogenetic neural manipulation is a powerful tool that enables brain-wide mapping of effective functional networks. To achieve flexible manipulation of neural excitation throughout the mouse cortex, we incorporated spatiotemporal programmable optogenetic stimuli generated by a digital micromirror device into an MRI scanner via an optical fiber bundle. This approach offered versatility in space and time in planning the photostimulation pattern, combined with in situ optical imaging and cell-type-specific or circuit-specific genetic targeting in individual mice. Brain-wide effective connectivity obtained by fMRI with optogenetic stimulation of atlas-based cortical regions is generally congruent with anatomically defined axonal tracing data but is affected by the types of anesthetics that act selectively on specific connections. fMRI combined with flexible optogenetics opens a new path to investigate dynamic changes in functional brain states in the same animal through high-throughput brain-wide effective connectivity mapping. © 2023 Elsevier Inc.11Nsciescopu
Protocol for mouse optogenetic fMRI at ultrahigh magnetic fields
No full textMouse optogenetic functional magnetic resonance imaging (opto-fMRI) is critical for linking genes and functions and for mapping cell-type-specific neural circuits in the whole brain. Herein, we describe how opto-fMRI images can be reliably obtained in anesthetized mice with minimal distortions at ultrahigh magnetic fields. The protocol includes surgical and anesthesia procedures, animal cradle modification, animal preparation and setup, animal physiology maintenance, and pilot fMRI scanning. This protocol will enable reproducible mouse opto-fMRI experiments. For complete details on the use and execution of this protocol, please refer to Jung et al. (2021),1 Jung et al. (2022),2 and Moon et al. (2021).3 © 2022 The Author(s)11Nscopu
General‐Purpose Ultrasound Neuromodulation System for Chronic, Closed‐Loop Preclinical Studies in Freely Behaving Rodents
No full textTranscranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head‐fixed, anesthesia‐dependent, and acute, limiting clinical translatability. Here, this work reports a general‐purpose ultrasound neuromodulation system for chronic, closed‐loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact‐free stimulation and simultaneous neural recording. Using the general‐purpose system, it can be observed that state‐dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption
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