A radical containing micellar probe for assessing esterase enzymatic activity with ultra-low field Overhauser-enhanced magnetic resonance imaging.

The ability to track altered enzyme activity using a non-invasive imaging protocol is crucial for the early diagnosis of many diseases but is often challenging. Herein, we show that Overhauser magnetic resonance imaging (OMRI) can be used to monitor enzymatic conversion at an ultra-low field (206 μT) using a highly sensitive "off/on" probe with a nitroxide stable radical containing ester, named T2C-T80. This TEMPO derivative containing probe forms stable electron paramagnetic resonance (EPR) silent micelles in water that are hydrolysed by esterases, thus yielding narrow EPR signals whose intensities correlate directly with specific enzymatic activity.

A system for in vivo on-demand ultra-low field Overhauser-enhanced 3D-Magnetic resonance imaging.

Development of very-low field MRI is an active area of research. It aims at reducing operating costs and improve portability. However, the signal-to-noise issue becomes prominent at ultra-low field (<1 mT), especially for molecular imaging purposes that addresses specific biochemical events.

2D multislice MP2RAGE sequence for fast T mapping at 7 T: Application to mouse imaging and MR thermometry.

Purpose: To develop a 2D radial multislice MP2RAGE sequence for fast and reliable T mapping at 7 T in mice and for MR thermometry.

Methods: The 2D-MP2RAGE sequence was performed with the following parameters: TI -TI -MP2RAGE = 1000-3000-9000 ms. The multiple dead times within the sequence were used for interleaved multislice acquisition, enabling one to acquire six slices in 9 seconds.

An elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting nitroxide.

Pulmonary inflammatory diseases are a major burden worldwide. They have in common an influx of neutrophils. Neutrophils secrete unchecked proteases at inflammation sites consequently leading to a protease/inhibitor imbalance.

Selective On/Off-Nitroxides as Radical Probes to Investigate Non-radical Enzymatic Activity by Electron Paramagnetic Resonance.

A nitroxide carrying a peptide specific to the binding pocket of the serine proteases chymotrypsin and cathepsin G is prepared. This peptide is attached as an enol ester to the nitroxide. Upon enzymatic hydrolysis of the peptide, the enol ester moiety is transformed into a ketone moiety.

Circulating bacterial lipopolysaccharide-induced inflammation reduces flow in brain-irrigating arteries independently from cerebrovascular prostaglandin production.

Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-κB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as prostaglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals.

In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence.

Although MEMRI (Manganese Enhanced MRI) informations were obtained on primary tumors in small animals, MEMRI data on metastases are lacking. Thus, our goal was to determine if 3D Look-Locker T1 mapping was an efficient method to evaluate Mn ions transport in brain metastases in vivo. The high spatial resolution in 3D (156 × 156 × 218 μm) of the sequence enabled to detect metastases of 0.

Fast 3D ultrashort echo-time spiral projection imaging using golden-angle: A flexible protocol for in vivo mouse imaging at high magnetic field.

Purpose: To develop a fast three-dimensional (3D) k-space encoding method based on spiral projection imaging (SPI) with an interleaved golden-angle approach and to validate this novel sequence on small animal models.

Methods: A disk-like trajectory, in which each disk contained spirals, was developed. The 3D encoding was performed by tilting the disks with a golden angle.

USPIO-enhanced 3D-cine self-gated cardiac MRI based on a stack-of-stars golden angle short echo time sequence: Application on mice with acute myocardial infarction.

Purpose: To develop and assess a 3D-cine self-gated method for cardiac imaging of murine models.

Materials And Methods: A 3D stack-of-stars (SOS) short echo time (STE) sequence with a navigator echo was performed at 7T on healthy mice (n = 4) and mice with acute myocardial infarction (MI) (n = 4) injected with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. In all, 402 spokes were acquired per stack with the incremental or the golden angle method using an angle increment of (360/402)° or 222.

Free-breathing 3D diffusion MRI for high-resolution hepatic metastasis characterization in small animals.

The goal of this study was to develop a 3D diffusion weighted sequence for free breathing liver imaging in small animals at high magnetic field. Hepatic metastases were detected and the apparent diffusion coefficients (ADC) were measured. A 3D SE-EPI sequence was developed by (i) inserting a water-selective excitation radiofrequency pulse to suppress adipose tissue signal and (ii) bipolar diffusion gradients to decrease the sensitivity to respiration motion.

Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small Animals at 3T and 7T, Respectively.

Introduction: The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field.

Methods: In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7 T and 3 T, respectively to perform whole-body and musculoskeletal imaging.

The β-phosphorus hyperfine coupling constant in nitroxide: part 3: titration of water by electron paramagnetic resonance.

Recently, we showed that the phosphorus hyperfine coupling constant aPβ of persistent cyclic nitroxides decreased with the normalized polarity Reichardt's constant E. Thus, we investigated the changes in aPβ in binary mixtures of solvents. The sensitivity of aPβ to the solvent was high enough to allow us to perform water titration in THF, 1,4-dioxane, and acetonitrile by EPR.

Enzymatically Shifting Nitroxides for EPR Spectroscopy and Overhauser-Enhanced Magnetic Resonance Imaging.

In vivo investigations of enzymatic processes using non-invasive approaches are a long-lasting challenge. Recently, we showed that Overhauser-enhanced MRI is suitable to such a purpose. A β-phosphorylated nitroxide substrate prototype exhibiting keto-enol equilibrium upon enzymatic activity has been prepared.

Positive contrast high-resolution 3D-cine imaging of the cardiovascular system in small animals using a UTE sequence and iron nanoparticles at 4.7, 7 and 9.4 T.

Background: To show that 3D sequences with ultra-short echo times (UTEs) can generate a positive contrast whatever the magnetic field (4.7, 7 or 9.4 T) and whatever Ultra Small Particles of Iron Oxide (USPIO) concentration injected and to use it for 3D time-resolved imaging of the murine cardiovascular system with high spatial and temporal resolutions.

Fast and robust 3D T1 mapping using spiral encoding and steady RF excitation at 7 T: application to cardiac manganese enhanced MRI (MEMRI) in mice.

Mapping longitudinal relaxation times in 3D is a promising quantitative and non-invasive imaging tool to assess cardiac remodeling. Few methods are proposed in the literature allowing us to perform 3D T1 mapping. These methods often require long scan times and use a low number of 3D images to calculate T1 .

Self-gated bSSFP sequences to detect iron-labeled cancer cells and/or metastases in vivo in mouse liver at 7 Tesla.

Background: To develop and evaluate three-dimensional (3D) self-gated balanced steady state free precession (bSSFP) imaging at high magnetic fields to track iron-labeled cells and metastases in murine abdomens.

Methods: Mice were injected intravenously with iron-labeled melanoma cells and imaged at 7 Tesla (T). Respiration peaks were identified using Free Induction Decay acquired immediately after the radiofrequency pulse.

Alkoxyamines: toward a new family of theranostic agents against cancer.

Theranostics combines therapeutic and diagnostic or drug deposition monitoring abilities of suitable molecules. Here we describe the first steps of building an alkoxyamine-based theranostic agent against cancer. The labile alkoxyamine ALK-1 (t(1/2) = 50 min at 37 °C) cleaves spontaneously to generate (1) a highly reactive free alkyl radical used as therapeutic agents to induce cell damages leading to cell death and (2) a stable nitroxide used as contrast agent for Overhauser-enhanced magnetic resonance imaging (OMRI).

Contribution of pyruvate phosphate dikinase in the maintenance of the glycosomal ATP/ADP balance in the Trypanosoma brucei procyclic form.

Trypanosoma brucei belongs to a group of protists that sequester the first six or seven glycolytic steps inside specialized peroxisomes, named glycosomes. Because of the glycosomal membrane impermeability to nucleotides, ATP molecules consumed by the first glycolytic steps need to be regenerated in the glycosomes by kinases, such as phosphoenolpyruvate carboxykinase (PEPCK). The glycosomal pyruvate phosphate dikinase (PPDK), which reversibly converts phosphoenolpyruvate into pyruvate, could also be involved in this process.

In vivo Overhauser-enhanced MRI of proteolytic activity.

There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.

Time-resolved TOF MR angiography in mice using a prospective 3D radial double golden angle approach.

Purpose: To develop an undersampled anatomical, three-dimensional (3-D) time-resolved magnetic resonance angiography (MRA) method for small animals based on time-of-flight (TOF) effect and radial sampling.

Methods: Mouse carotid arteries and Circle of Willis images were acquired on a 7T scanner with an electrocardiogram (ECG)-triggered sequence. Preliminary experiments were used to generate an approximately uniform distribution of radial projections with a first golden angle and to produce anatomical TOF images.

Cellular density effect on RGD ligand internalization in glioblastoma for MRI application.

Cellular density is a parameter measured for glioma grade and invasiveness diagnosis. The characterization of the cellular density can be performed, non invasively, by magnetic resonance imaging (MRI), since, this technique displays a good resolution. Nevertheless MRI sensitivity is critical.

Revisiting the central metabolism of the bloodstream forms of Trypanosoma brucei: production of acetate in the mitochondrion is essential for parasite viability.

Background: The bloodstream forms of Trypanosoma brucei, the causative agent of sleeping sickness, rely solely on glycolysis for ATP production. It is generally accepted that pyruvate is the major end-product excreted from glucose metabolism by the proliferative long-slender bloodstream forms of the parasite, with virtually no production of succinate and acetate, the main end-products excreted from glycolysis by all the other trypanosomatid adaptative forms, including the procyclic insect form of T. brucei.

Alkoxyamines: a new family of pro-drugs against cancer. Concept for theranostics.

Development of anti-cancerous theranostic agents is a vivid field. This article describes a theranostic approach that relies on the triggering of cancer cell death by generation of alkyl radicals at the right place and at the right time using the presence of active proteases in the tumour environment. Alkoxyamines (R(1)R(2)NOR(3)) are labile molecules that homolyze into nitroxides (R(1)R(2)NO˙) and reactive alkyl radicals (R(3)˙).

Mitochondrial energetics is impaired in vivo in aged skeletal muscle.

With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle.

The threonine degradation pathway of the Trypanosoma brucei procyclic form: the main carbon source for lipid biosynthesis is under metabolic control.

The Trypanosoma brucei procyclic form resides within the digestive tract of its insect vector, where it exploits amino acids as carbon sources. Threonine is the amino acid most rapidly consumed by this parasite, however its role is poorly understood. Here, we show that the procyclic trypanosomes grown in rich medium only use glucose and threonine for lipid biosynthesis, with threonine's contribution being ∼ 2.