Automatic Adaptive Algorithm for Delineation of Cerebral-Spinal Fluid Regions for Non-contrast Magnetic Resonance Imaging Volumetry and Cisternography in Mice.

Magnetic resonance imaging (MRI) is an invaluable method of choice for anatomical and functional in vivo imaging of the brain. Still, accurate delineation of the brain structures remains a crucial task of MR image evaluation. This study presents a novel analytical algorithm developed in MATLAB for the automatic segmentation of cerebrospinal fluid (CSF) spaces in preclinical non-contrast MR images of the mouse brain.

Protocol to study oxygen dynamics in the in vivo mouse brain using bioluminescence microscopy.

Bioluminescence imaging (BLI) relies on the biochemical reaction between substrate and enzyme that triggers light emission upon convergence. Here, we present a protocol to study molecular oxygen dynamics in the in vivo mouse brain using the oxygen-dependent reaction between luciferase and its substrate. We describe steps for acute craniotomy, viral transfection, substrate administration, imaging, and analysis of hypoxic pockets.

Glymphatic clearance is enhanced during sleep.

We here revisited the concept that glymphatic clearance is enhanced by sleep and anesthesia. Utilizing dynamic magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and fluorescent fiber photometry, we report brain glymphatic clearance is enhanced by both sleep and anesthesia, and sharply suppressed by wakefulness. Another key finding was that less tracer enters the brains of awake animals and that brain clearance across different brain states can only be compared after adjusting for the injected tracer dose.

Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood.

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days.

Transient but not chronic hyperglycemia accelerates ocular glymphatic transport.

Glymphatic transport is vital for the physiological homeostasis of the retina and optic nerve. Pathological alterations of ocular glymphatic fluid transport and enlarged perivascular spaces have been described in glaucomatous mice. It remains to be established how diabetic retinopathy, which impairs vision in about 50% of diabetes patients, impacts ocular glymphatic fluid transport.

Glymphatic fluid transport is suppressed by the aquaporin-4 inhibitor AER-271.

The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin-4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space.

Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice.

Inner ear gene therapy has recently effectively restored hearing in neonatal mice, but it is complicated in adulthood by the structural inaccessibility of the cochlea, which is embedded within the temporal bone. Alternative delivery routes may advance auditory research and also prove useful when translated to humans with progressive genetic-mediated hearing loss. Cerebrospinal fluid flow via the glymphatic system is emerging as a new approach for brain-wide drug delivery in rodents as well as humans.

Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.

The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport.

A mesothelium divides the subarachnoid space into functional compartments.

The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells.

Advanced diffusion imaging of abdominal organs in different hydration states of the human body: stability of biomarkers.

Background: MR diffusion weighted imaging (DWI) may provide important information regarding the pathophysiology of parenchymal abdominal organs. The purpose of our study was to investigate the stability of imaging biomarkers of diffusion weighted imaging (DWI), intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in abdominal parenchymal organs regarding two body hydration states.

Methods: Ten healthy volunteers twice underwent DWI of abdominal organs using a double-refocused spin-echo echo-planar imaging sequences with 11 different b-values (ranging from 0 to 1,500 s/mm): after 4 h of fluid deprivation; 45 min following 1000 ml of water intake.

Mapping of CSF transport using high spatiotemporal resolution dynamic contrast-enhanced MRI in mice: Effect of anesthesia.

Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) represents the only available approach for glymphatic cerebrospinal fluid (CSF) flow 3D mapping in the brain of living animals and humans. The purpose of this study was to develop a novel DCE-MRI protocol for mapping of the glymphatic system transport with improved spatiotemporal resolution, and to validate the new protocol by comparing the transport in mice anesthetized with either isoflurane or ketamine/xylazine.

Methods: The contrast agent, gadobutrol, was administered into the CSF of the cisterna magna and its transport visualized continuously on a 9.

Evaluation of Urinary Sphincter Function by Rapid Magnetic Resonance Diffusion Tensor Imaging.

Purpose: This study aimed to assess the feasibility of a rapid diffusion tensor imaging (DTI) for evaluation of the female urinary sphincter function based on differentiation between rest and muscle contraction.

Methods: Magnetic resonance imaging (MRI) of the lower pelvis was performed at 3 Tesla in 10 healthy female volunteers (21-36 years; body mass index, 20.8±3.

Na-T quantification with saturation recovery TrueFISP and variable flip angle GRE at 3T: A phantom study.

Purpose: The aim of the current study was to compare the reproducibility of sodium ( Na)-T estimation using a centric-reordered saturation recovery (SR) true fast imaging with steady-state precession (TrueFISP) and a variable flip angle (VFA) spoiled gradient echo (GRE). Additionally, we evaluated the effect of spatial averaging on Na-T estimation by the two methods.

Methods: Measurements were performed in the phantom, consisting of 10 dm volume rectangular polyethylene container filled with distilled water solution of 0.

Quantification of sodium T1 in abdominal tissues at 3 T.

Introduction: Although relevant for assessment of sodium in multiple endocrine pathways, Na-T1 quantification is challenging due to technical limitations (SAR, B1 inhomogeneity) or influence of tissue's local molecular dynamics. Hereby, we propose T1 quantification of Na-MRI signal acquired over the abdomen using a centric-reordered saturation-recovery (SR) true fast imaging with steady state precession (TrueFISP) sequence.

Materials And Methods: Measurements were performed at 3T using a dual-tunable Na/H coil in 7 healthy volunteers (TR/TE = 858-928/1.

Higuchi Fractal Dimension of Heart Rate Variability During Percutaneous Auricular Vagus Nerve Stimulation in Healthy and Diabetic Subjects.

Analysis of heart rate variability (HRV) can be applied to assess the autonomic nervous system (ANS) sympathetic and parasympathetic activity. Since living systems are non-linear, evaluation of ANS activity is difficult by means of linear methods. We propose to apply the Higuchi fractal dimension (HFD) method for assessment of ANS activity.

Computer analysis of histopathological images for tumor grading.

Objective: We developed a new method that enables automatic and rapid assessment of a tumor's proliferation index from immunohistochemically (IHC) stained microscopic images.

Approach: The method is based on computer-aided analysis of images - color filtration pixel-by-pixel (CFPP method) of the whole histopathological virtual slides.

Main Results: The method is simple, rapid, and does not require the time consuming step of selecting manually areas of interest nor the need for computationally complicated detection of hot-spots, both of which attempt to emulate a pathologist's way of estimating a proliferation index.

Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity.

Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy.

A Quantitative Method Using Head Noncontrast CT Scans to Detect Hyperacute Nonvisible Ischemic Changes in Patients With Stroke.

Purpose: Because clinical evaluation of noncontrast computed tomography (CT) has a poor sensitivity in the evaluation of acute ischemic stroke, computer-aided diagnosis may be able to facilitate the performance. Recently, we introduced a computational method for the detection and localization of visible infarcts. Herein, we aimed to evaluate and extend a previous method, the Stroke Imaging Marker (SIM), to localize nonvisible hyperacute ischemia.

The role of apelin in central cardiovascular regulation in rats with post-infarct heart failure maintained on a normal fat or high fat diet.

Based on the available literature, it can be assumed that in cases of post-infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin-13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies.

Reduction of pressor response to stress by centrally acting apelin in spontaneously hypertensive rats.

Background: Numerous studies suggest that apelin plays a significant role in cardiovascular regulation and in the pathogenesis of hypertension. The purpose of the present study was to determine whether apelin-13 (AP-13) is involved in the regulation of cardiovascular responses to acute stress in spontaneous hypertension.

Methods: The effects of intracerebroventricular (ICV) administration of AP-13 on changes in mean arterial blood pressure (MABP) and heart rate evoked by an alarming stress (air jet stress) were compared in awake normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague-Dawley rats.

Central application of apelin elevates blood pressure and influences neuroendocrine responses to stress and food consumption. However, it is not known whether the central cardiovascular effects of apelin depend also on caloric intake or chronic stress. The purpose of the present study was to determine the effects of intracerebroventricular administration of apelin on blood pressure (mean arterial blood pressure) and heart rate in conscious Sprague-Dawley rats consuming either a normal-fat diet (NFD) or high-fat diet (HFD) for 12 weeks.

Characterization of intraventricular and intracerebral hematomas in non-contrast CT.

Characterization of hematomas is essential in scan reading, manual delineation, and designing automatic segmentation algorithms. Our purpose is to characterize the distribution of intraventricular (IVH) and intracerebral hematomas (ICH) in NCCT scans, study their relationship to gray matter (GM), and to introduce a new tool for quantitative hematoma delineation. We used 289 serial retrospective scans of 51 patients.

[The role of apelin in pathogenesis of cardiovascular diseases and metabolic disorders].

Apelin is a recently discovered biologically active peptide present in several isoforms that are agonists for orphan receptor APJ. Apelin and APJ receptor were found in the central nervous system and in different peripheral tissues. In the cardiovascular system the peptide is present both in the heart and in the endothelium and smooth muscles cells of the vascular wall.

Brain vasopressin V(1) receptors contribute to enhanced cardiovascular responses to acute stress in chronically stressed rats and rats with myocardial infarcton.

The present study was designed to determine the role of central vasopressin 1 receptors (V(1)R) in the regulation of cardiovascular parameters in chronically stressed infarcted rats and sham-operated rats under resting conditions and during exposure to acute alarming stress. The experiments were performed on four groups of conscious sham-operated and four groups of infarcted rats subjected to intraventricular infusion of either vehicle or a V(1)R antagonist (V(1)RANT). Two groups of infarcted and two groups of sham-operated rats were subjected to mild chronic stressing.