Size-Controlled Self-Assembly for Bimodal In Vivo Imaging.

Contrast agents (CAs) are essential in biomedical imaging to aid in the diagnosis and therapy monitoring of disease. However, they are typically restricted to one imaging modality and have fixed properties such as size, shape, toxicity profile, or photophysical characteristics, which hampers a comprehensive view of biological processes. Herein, rationally designed dye assemblies are introduced as a unique CA platform for simultaneous multimodal and multiscale biomedical imaging.

Deficiency of the palmitoyl acyltransferase ZDHHC7 modulates depression-like behaviour in female mice after a mild chronic stress paradigm.

Chronic stress (CS) is a debilitating condition that negatively affects body and brain. In mice, CS effects range from changes in behaviour and brain microstructure down to the level of gene expression. These effects are partly mediated by sex and sex steroid hormones, which in turn are affected by the palmitoyl acyltransferase ZDHHC7.

How spinal GABAergic circuits modulate cerebral processing of postsurgical pain.

Post-surgical pain affects millions each year, hindering recovery and quality of life. Surgical procedures cause tissue damage and inflammation, leading to peripheral and central sensitization, resulting in pain at rest or mechanical and heat hyperalgesia. In a rat model for post-surgical pain, spinal GABAergic transmission via GABA receptors reduces mechanical hypersensitivity but has no effect on pain at rest.

Systematic evaluation of adhesives for implant fixation in multimodal functional brain MRI.

Objective: Invasive multimodal fMRI in rodents is often compromised by susceptibility artifacts from adhesives used to secure cranial implants. We hypothesized that adhesive type, shape, and field strength significantly affect susceptibility artifacts, and systematically evaluated various adhesives.

Materials And Methods: Thirty-one adhesives were applied in constrained/unconstrained geometries and imaged with T2*-weighted EPI at 7.

Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats.

Although the pathophysiology of pain has been investigated tremendously, there are still many open questions with regard to specific pain entities and their pain-related symptoms. To increase the translational impact of (preclinical) animal neuroimaging pain studies, the use of disease-specific pain models, as well as relevant stimulus modalities, are critical. We developed a comprehensive framework for brain network analysis combining functional magnetic resonance imaging (MRI) with graph-theory (GT) and data classification by linear discriminant analysis.

Microglial activation without peripheral immune cell infiltration characterises mouse and human cerebral small vessel disease.

Aims: Cerebral small vessel diseases (SVDs) involve diverse pathologies of the brain's small blood vessels, leading to cognitive deficits. Cerebral magnetic resonance imaging (MRI) reveals white matter hyperintensities (WMHs), lacunes, microbleeds and enlarged perivascular spaces in SVD patients. Although correlations of MRI and histopathology help to understand the pathogenesis of SVD, they do not explain disease progression.

A dietary intervention with conjugated linoleic acid enhances microstructural white matter reorganization in experimental stroke.

Background: A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (T) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since T and anti-inflammatory (M2-type) macrophages were found to enhance stroke recovery, we hypothesized that CLA-supplementation might improve stroke recovery via immune modulatory effects.

Methods: Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice ( = 37, sham  = 10).

P-based referencing for correcting tissue artifacts in laser ablation-inductively coupled plasma-mass spectrometry imaging of cancer samples.

A referencing strategy based on the element P is presented to compensate for cryosectioning tissue artifacts in laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) data. The study examines how the gadolinium-based contrast agent Gadofosveset is distributed in murine cancer tissue, and illustrates how referenced images can compensate for tissue artifacts like folds, overlaps, and density variations. Compared to non-referenced images that provide information on the absolute distribution of the analyte, referenced images allow for the representation of the analyte distribution relative to the amount of material introduced into the instrument, which in this case is correlated to the P signal.

Engineered SPIONs functionalized with endothelin a receptor antagonist ameliorate liver fibrosis by inhibiting hepatic stellate cell activation.

Endothelin-1/endothelin A receptor (ET-1/ETAR) pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells (HSCs) - a key cell type involved in the pathogenesis of liver fibrosis. Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist (ERA) represents a promising therapeutic approach for liver fibrosis. Unfortunately, small-molecule ERAs possess limited clinical potential due to poor bioavailability, short half-life, and rapid renal clearance.

Endurance Training Provokes Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Heterozygous Desmoglein-2 Mutants: Alleviation by Preload Reduction.

Desmoglein-2 mutations are detected in 5-10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous mutant mice develop a severe ARVC-like phenotype.

Multiparametric MRI for characterization of the tumour microenvironment.

Our understanding of tumour biology has evolved over the past decades and cancer is now viewed as a complex ecosystem with interactions between various cellular and non-cellular components within the tumour microenvironment (TME) at multiple scales. However, morphological imaging remains the mainstay of tumour staging and assessment of response to therapy, and the characterization of the TME with non-invasive imaging has not yet entered routine clinical practice. By combining multiple MRI sequences, each providing different but complementary information about the TME, multiparametric MRI (mpMRI) enables non-invasive assessment of molecular and cellular features within the TME, including their spatial and temporal heterogeneity.

Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy.

Introduction: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-functional magnetic resonance imaging (rs-fMRI) and manganese-enhanced MRI (MEMRI) combined with morphometry, and to investigate potential brain network alterations, following long-term seizure activity.

Methods: Repeated rs-fMRI measurements at 9.

Corrections for Rabi oscillations in cardiac chemical exchange saturation transfer MRI under the influence of very short preparation pulses.

Very short chemical exchange saturation transfer (CEST) pulses are beneficial in cardiac continuous wave (cw) CEST MRI, especially in small animals because of their rapid heartbeat; however, they result in signal modulations caused by Rabi oscillations. Therefore, we implemented two different filter techniques, DOwnsampling by SEparation of CEST spectrum into two parts (DOSE) and time domain (TD)-based filtering, to correct for these signal corruptions, allowing a reliable quantification of glucose-weighted CEST (glucoCEST) MRI contrast. In our study, cw CEST measurements were performed on a 9.

Radial compressed sensing imaging improves the velocity detection limit of single cell tracking time-lapse MRI.

Purpose: Time-lapse MRI enables tracking of single iron-labeled cells. Yet, due to temporal blurring, only slowly moving cells can be resolved. To study faster cells for example during inflammatory processes, accelerated acquisition is needed.

Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI.

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes.

Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy.

Background: With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy.

Methods: Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated.

Dynamic cell tracking using time-lapse MRI with variable temporal resolution Cartesian sampling.

Purpose: Temporal resolution of time-lapse MRI to track individual iron-labeled cells is limited by the required data-acquisition time to fill k-space and to reach sufficient SNR. Although motion of slowly patrolling monocytes can be resolved, detection of fast-moving immune cells requires improved acquisition and reconstruction strategies.

Theory And Methods: For accelerated MRI cell tracking, a Cartesian sampling scheme was designed, in which the fully sampled and undersampled k-space data for different acceleration factors were acquired simultaneously, and multiple undersampling ratios could be chosen retrospectively.

Disentangling the impact of cerebrospinal fluid formation and neuronal activity on solute clearance from the brain.

Background: Despite recent attention, pathways and mechanisms of fluid transposition in the brain are still a matter of intense discussion and driving forces underlying waste clearance in the brain remain elusive. Consensus exists that net solute transport is a prerequisite for efficient clearance. The individual impact of neuronal activity and cerebrospinal fluid (CSF) formation, which both vary with brain state and anesthesia, remain unclear.

Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy.

Background: Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.

A Carboxy-terminal Smarcb1 Point Mutation Induces Hydrocephalus Formation and Affects AP-1 and Neuronal Signalling Pathways in Mice.

The BAF (BRG1/BRM-associated factor) chromatin remodelling complex is essential for the regulation of DNA accessibility and gene expression during neuronal differentiation. Mutations of its core subunit SMARCB1 result in a broad spectrum of pathologies, including aggressive rhabdoid tumours or neurodevelopmental disorders. Other mouse models have addressed the influence of a homo- or heterozygous loss of Smarcb1, yet the impact of specific non-truncating mutations remains poorly understood.

EXERTION: a pilot trial on the effect of aerobic, smartwatch-controlled exercise on stroke recovery: effects on motor function, structural repair, cognition, mental well-being, and the immune system.

Introduction: Motor impairments are the objectively most striking sequelae after stroke, but non-motor consequences represent a high burden for stroke survivors as well. Depression is reported in one third of patients, the fatigue prevalence ranges from 23 to 75% due to heterogenous definitions and assessments. Cognitive impairment is found in one third of stroke patients 3-12 months after stroke and the risk for dementia is doubled by the event.