GlyCEST: Magnetic Resonance Imaging of Glycine-Distribution in the Normal Murine Brain and Alterations in 5xFAD Mice.

The glycine level in the brain is known to be altered in neuropsychiatric disorders, such as schizophrenia and Alzheimer's disease (AD). Several studies have reported the measurement of glycine concentrations in the brain using proton magnetic resonance spectroscopy (H-MRS), but H-MRS is not capable of imaging the distribution of glycine concentration with high spatial resolution. Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is a new technology that can detect specific molecules, including amino acids, in tissues.

Longitudinal GluCEST MRI Changes and Cerebral Blood Flow in 5xFAD Mice.

Many of the focal neurological symptoms associated with Alzheimer's disease (AD) are due to synaptic loss. Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) is a candidate method to assess synaptic dysfunction. We assessed chronological changes in GluCEST in a 5xFAD mouse model of AD, comparing Glucest effects and regional cerebral blood flow (CBF).

Skull diploë is rich in aquaporin-4.

Aquaporin-4 (AQP4) is a water conducting membrane integral protein channel which is widely expressed in the astrocyte system of the brain. During the development of the AQP4 positron emission tomography (PET) imaging agent [C]TGN-020 (-(1,3,4-thiadiazol-2-yl)pyridine-3-[C]-carboxamide), significant radioligand uptake was observed in the skull, where there was no known distribution of any aquaporin family proteins. Herein we confirmed via a newly developed method for bone-tissue immunohistology, a hitherto unrecognized distribution of AQP4, and not AQP1, in the skull.

Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo F-Magnetic Resonance Spectroscopic Imaging.

Matrix metalloproteinases (MMPs) damage the neurovascular unit, promote the blood-brain barrier (BBB) disruption following ischemic stroke, and play essential roles in hemorrhagic transformation (HT), which is one of the most severe side effects of thrombolytic therapy. However, no biomarkers have presently been identified that can be used to track changes in the distribution of MMPs in the brain. Here, we developed a new F-molecular ligand, TGF-019, for visualizing the distribution of MMPs in vivo using F-magnetic resonance spectroscopic imaging (F-MRSI).

Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain.

The discovery of the water specific channel, aquaporin, and abundant expression of its isoform, aquaporin-4 (AQP-4), on astrocyte endfeet brought about significant advancements in the understanding of brain fluid dynamics. The brain is protected by barriers preventing free access of systemic fluid. The same barrier system, however, also isolates brain interstitial fluid from the hydro-dynamic effect of the systemic circulation.

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid.

Musical pitch classes have rainbow hues in pitch class-color synesthesia.

Synesthesia, an anomalous blending of senses in which stimulation of one sensory modality produces sensation in a different modality, provides a unique opportunity to study how multimodal information is represented in the human brain. We investigated how pitch classes (do, re, mi, etc.) are associated with the three dimensions of color (hue, saturation, and value/brightness) in 15 subjects who possessed "pitch class-color synesthesia".

Inferior colliculus syndrome: Clinical magnetic resonance microscopy anatomic analysis on a 7 T system.

We performed detailed structural analysis of a case of a unilateral lesion of the inferior colliculus using magnetic resonance microscopy on a 7 T system. A 36-year-old right-handed man had an intracerebral hemorrhage circumscribed to the right inferior colliculus. Following recovery from the acute phase, he had only residual left ear tinnitus and left trochlear palsy and no hearing loss.

MRI characteristics of the glia limitans externa: A 7T study.

Purpose: To perform a systematic analysis of the intrinsic contrast parameters of the FLAIR hyperintense rim (FHR), a thin layer of high intensity covering the entire surface of the cerebral cortex detected on fluid-attenuated inversion recovery (FLAIR) sequence T weighted imaging performed on a 7T system, in an attempt to identify its anatomical correlate.

Methods: Fast spin echo inversion recovery (FSE-IR) and cardiac-gated fast spin echo (FSE) images were obtained with defined parameters in eight normal volunteers on a 7 T MRI system to determine T2 and proton density, T characteristics. K-means clustering analysis of parameter sets was performed using MATLAB version R2015b for the purpose of identifying the cluster reflecting FHR.

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries.

Aquaporin Positron Emission Tomography Differentiates Between Grade III and IV Human Astrocytoma.

Background: Aquaporin (AQP) water channels play a significant role in mesenchymal microvascular proliferation and infiltrative growth. AQPs are highly expressed in malignant astrocytomas, and a positive correlation is observed between their expression levels and histological tumor grade.

Objective: To examine the utility of aquaporin positron emission tomography (PET) for differentiating between astrocytoma grade III and grade IV using the AQP radioligand [11C]TGN-020.

Reduced CSF Water Influx in Alzheimer's Disease Supporting the β-Amyloid Clearance Hypothesis.

Objective: To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer's patients as previously shown in the transgenic mouse model for Alzheimer's disease.

Methods: Ten normal young volunteers (young control, 21-30 years old), ten normal senior volunteers (senior control, 60-78 years old, MMSE ≥ 29), and ten Alzheimer's disease (AD) patients (study group, 59-84 years old, MMSE: 13-19) participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria.

Covert effects of "one drink" of alcohol on brain processes related to car driving: an event-related potential study.

The effects of a low dose of alcohol on car driving remain controversial. To address this issue, event-related potentials were recorded while subjects performed a simple car-following task in a driving simulator before and after consuming either "one drink" of beer (representing one standard alcoholic beverage containing 14 g of alcohol) or mineral water (control condition). Subjects who had consumed the determined amount of alcohol demonstrated no detectable outward behavioral signs of intoxication while performing the driving task, an observation in agreement with previous findings.

Ligand-based molecular MRI: O-17 JJVCPE amyloid imaging in transgenic mice.

Background: Development of molecular MR imaging (MRI) similar to PET imaging using contrast agents such as gadolinium as probe have been inherently hampered by incompatibility between potential probe (charged molecules) and membrane permeability. Nevertheless, considering the inherent spatial resolution limit for PET of 700μ, the superior microscopic resolution of MRI of 4 μ presents a strong incentive for research into ligand-based molecular MRI.

Methods: (17) O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group.

Water influx into cerebrospinal fluid is significantly reduced in senile plaque bearing transgenic mice, supporting beta-amyloid clearance hypothesis of Alzheimer's disease.

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water influx into the peri-capillary (Virchow-Robin) space through aquaporin 4 (AQP-4). This water flow is believed to have the functionality equivalent to the systemic lymphatic system and plays a critical role in beta-amyloid clearance. Using a newly developed molecular imaging technique capable of tracing water molecules, in vivo, water influx into the CSF was quantitatively analyzed in senile plaque (SP) bearing transgenic Alzheimer's disease (AD) model mice.

Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not by aquaporin-1: 17O JJVCPE MRI study in knockout mice.

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow-Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo.

Inhibition of aquaporin-4 significantly increases regional cerebral blood flow.

The effects of the aquaporin-4 (AQP-4) inhibitor TGN-020 on regional cerebral blood flow (rCBF) was examined in wild-type (WT) and AQP-4 knockout (KO) mice in vivo. Although baseline absolute rCBF of WT and KO mice were equivalent (158.9 ± 17.

Effects of musical training on the early auditory cortical representation of pitch transitions as indexed by change-N1.

The effects of musical training on the early auditory cortical response to pitch transitions in music were investigated by use of the change-N1 component of auditory event-related potentials. Musicians and non-musicians were presented with music stimuli comprising a melody and a harmony under various listening conditions. First, when the subjects played a video game and were instructed to ignore the auditory stimuli, the onset of stimuli elicited a typical, fronto-central onset-N1, whereas melodic and harmonic pitch transitions within the stimuli elicited so-called change-N1s that were more posterior in scalp distribution.

Neural strategies for reading Japanese and Chinese sentences: a cross-linguistic fMRI study of character-decoding and morphosyntax.

Japanese and Chinese share virtually identical morphographic characters invented in ancient China. Whereas modern Chinese retained the original morphographic functionality of these characters (hanzi), modern Japanese utilizes these characters (kanji) as complex syllabograms. This divergence provides a unique opportunity to systematically investigate brain strategies for sentence reading in Japanese-Chinese bi-literates.

Analysis of ascending spinal tract degeneration in cervical spondylotic myelopathy using 3D anisotropy contrast single-shot echo planar imaging on a 3.0-T system.

Object: The authors assessed the role of 3D anisotropy contrast (3DAC) in evaluating specific ascending tract degeneration in patients with cervical spondylotic myelopathy (CSM).

Methods: The authors studied 10 patients (2 women, 8 men; mean age 59.8 ± 14.

Expansion of corticomedullary junction high-susceptibility region (CMJ-HSR) with aging: a clue in the pathogenesis of Alzheimer's disease?

Background: Susceptibility-weighted imaging (SWI) microscopy on a 7.0T system demonstrated the corticomedullary junction (CMJ) to be a high-susceptibility region (HSR) in young normal subjects, suggesting that functional alteration of cortical microcirculation could be assessed with this imaging method.

Methods: Focused microscopic studies were performed on the parietal association cortex in 74 normal volunteers (ages 20-79 years; 35 female, 39 male) using a SWI algorithm on a system constructed based on General Electric Signa LX (Waukesha, WI, USA), equipped with a 900-mm clear bore superconducting magnet operating at 7.

Functional asymmetry in primary auditory cortex for processing musical sounds: temporal pattern analysis of fMRI time series.

Hemispheric differences in the temporal processing of musical sounds within the primary auditory cortex were investigated using functional magnetic resonance imaging (fMRI) time series analysis on a 3.0 T system in right-handed individuals who had no formal training in music. The two hemispheres exhibited a clear-cut asymmetry in the time pattern of fMRI signals.

Morphologic evaluation of the inferior alveolar nerve in patients with sensory disorders by high-resolution 3D volume rendering magnetic resonance neurography on a 3.0-T system.

Objective: The objective of this study was to evaluate the inferior alveolar nerve (IAN) morphologically in patients with symptomatic posttraumatic sensory disorders using magnetic resonance imaging (MRI) on a high-field system.

Study Design: Sixteen patients who complained of persistent sensory disturbance attributed to unilateral IAN injury participated in the investigation. High-resolution 3-dimensional volume rendering magnetic resonance neurography was performed on a 3.

Activity-dependent glial swelling is impaired in aquaporin-4 knockout mice.

We investigated the role of aquaporin-4 (AQP4), a water channel expressed in glial cells, in neural activity mediated morphological changes observed in brain slice preparation. Changes in flavoprotein fluorescence (FF) and infrared light scattering (LS) signals were measured before and after repetitive stimulation of layer VI in rostral somatosensory cortical slices taken from AQP4 knockout (KO) and wild-type (WT) mice. Changes in FF, which reflect neural aerobic activities, were comparable for the two groups in all cortical layers.

Participation of primary motor cortex area 4a in complex sensory processing: 3.0-T fMRI study.

The precise movement of human fingers requires continuous and reciprocal interaction between motor and sensory systems. Similar to other primates, there is double representation of the digits and wrists within the human primary motor cortex (M1), which are generally referred to as area 4 anterior (M1-4a) and area 4 posterior (M1-4p). In this high-field (3.