Iridium Cyclooctene Complex That Forms a Hyperpolarization Transfer Catalyst before Converting to a Binuclear C-H Bond Activation Product Responsible for Hydrogen Isotope Exchange.

[IrCl(COE)] (1) reacts with pyridine (py) and H to form crystallographically characterized IrCl(H)(COE)(py) (2). 2 undergoes py loss to form 16-electron IrCl(H)(COE)(py) (3), with equivalent hydride ligands. When this reaction is studied with parahydrogen, 1 efficiently achieves hyperpolarization of free py (and nicotinamide, nicotine, 5-aminopyrimidine, and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process.

A Hyperpolarizable H Magnetic Resonance Probe for Signal Detection 15 Minutes after Spin Polarization Storage.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are two extremely important techniques with applications ranging from molecular structure determination to human imaging. However, in many cases the applicability of NMR and MRI are limited by inherently poor sensitivity and insufficient nuclear spin lifetime. Here we demonstrate a cost-efficient and fast technique that tackles both issues simultaneously.

Creating a hyperpolarised pseudo singlet state through polarisation transfer from parahydrogen under SABRE.

The creation of magnetic states that have long lifetimes has been the subject of intense investigation, in part because of their potential to survive the time taken to travel from the point of injection in a patient to the point where a clinically diagnostic MRI trace is collected. We show here that it is possible to harness the signal amplification by reversible exchange (SABRE) process to create such states in a hyperpolarised form that improves their detectability in seconds without the need for any chemical change by reference to the model substrate 2-aminothiazole. We achieve this by transferring Zeeman derived polarisation that is 1500 times larger than that normally available at 400 MHz with greater than 90% efficiency into the new state, which in this case has a 27 second lifetime.

Molecular MRI in the Earth's Magnetic Field Using Continuous Hyperpolarization of a Biomolecule in Water.

In this work, we illustrate a method to continuously hyperpolarize a biomolecule, nicotinamide, in water using parahydrogen and signal amplification by reversible exchange (SABRE). Building on the preparation procedure described recently by Truong et al. [ J.

MEG Adaptation Resolves the Spatiotemporal Characteristics of Face-Sensitive Brain Responses.

Unlabelled: An unresolved goal in face perception is to identify brain areas involved in face processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques identify the fusiform gyrus as subserving processing of invariant face features relating to identity. High temporal resolution imaging techniques localize an early latency evoked component-the N/M170-as having a major generator in the fusiform region; however, this evoked component is not believed to be associated with the processing of identity.

Catalytic Transfer of Magnetism using a Neutral Iridium Phenoxide Complex.

A novel neutral iridium carbene complex Ir(κC,O-L)(COD) () [where COD = cyclooctadiene and L = 3-(2-methylene-4-nitrophenolate)-1-(2,4,6-trimethylphenyl) imidazolylidene] with a pendant alkoxide ligand has been prepared and characterized. It contains a strong Ir-O bond and X-ray analysis reveals a distorted square planar structure. NMR spectroscopy reveals dynamic solution state behavior commensurate with rapid seven-membered ring flipping.

Deactivation of signal amplification by reversible exchange catalysis, progress towards in vivo application.

The catalyst which is used in the signal amplification by reversible exchange (SABRE) process facilitates substrate hyperpolarisation while acting to speed up the rate of relaxation. Consequently, the lifetime over which the hyperpolarised contrast agent is visible is drastically reduced. We show that the addition of a chelating ligand, such as bipyridine, rapidly deactivates the SABRE catalyst thereby lengthening the agent's relaxation times and improving the potential of SABRE for diagnostic MRI.

Improving the hyperpolarization of (31)P nuclei by synthetic design.

Traditional (31)P NMR or MRI measurements suffer from low sensitivity relative to (1)H detection and consequently require longer scan times. We show here that hyperpolarization of (31)P nuclei through reversible interactions with parahydrogen can deliver substantial signal enhancements in a range of regioisomeric phosphonate esters containing a heteroaromatic motif which were synthesized in order to identify the optimum molecular scaffold for polarization transfer. A 3588-fold (31)P signal enhancement (2.

Strategies for the hyperpolarization of acetonitrile and related ligands by SABRE.

We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing (1)H and (13)C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality.

The reaction of an iridium PNP complex with parahydrogen facilitates polarisation transfer without chemical change.

The short lived pincer complex [(C5H3N(CH2P((t)Bu)2)2)Ir(H)2(py)]BF4 is shown to be active for signal amplification by reversible exchange. This catalyst formulation enables the efficient transfer of polarization from parahydrogen to be placed into just a single molecule of the hyperpolarisation target, pyridine. When the catalysts (1)H nuclei are replaced by (2)H, increased levels of substrate hyperpolarization result and when the reverse situation is examined the catalyst itself is clearly visible through hyperpolarised signals.

Probing signal amplification by reversible exchange using an NMR flow system.

Hyperpolarization methods are used in NMR to overcome its inherent sensitivity problem. Herein, the biologically relevant target nicotinamide is polarized by the hyperpolarization technique signal amplification by reversible exchange. We illustrate how the polarization transfer field, and the concentrations of parahydrogen, the polarization-transfer-catalyst and substrate can be used to maximize signal amplification by reversible exchange effectiveness by reference to the first-order spin system of this target.

Toward biocompatible nuclear hyperpolarization using signal amplification by reversible exchange: quantitative in situ spectroscopy and high-field imaging.

Signal amplification by reversible exchange (SABRE) of a substrate and parahydrogen at a catalytic center promises to overcome the inherent insensitivity of magnetic resonance. In order to apply the new approach to biomedical applications, there is a need to develop experimental equipment, in situ quantification methods, and a biocompatible solvent. We present results detailing a low-field SABRE polarizer which provides well-controlled experimental conditions, defined spins manipulations, and which allows in situ detection of thermally polarized and hyperpolarized samples.

Differential patterns of prefrontal MEG activation during verbal & visual encoding and retrieval.

The spatiotemporal profile of activation of the prefrontal cortex in verbal and non-verbal recognition memory was examined using magnetoencephalography (MEG). Sixteen neurologically healthy right-handed participants were scanned whilst carrying out a modified version of the Doors and People Test of recognition memory. A pattern of significant prefrontal activity was found for non-verbal and verbal encoding and recognition.

A hyperpolarized equilibrium for magnetic resonance.

Nuclear magnetic resonance spectroscopy and imaging (MRI) play an indispensable role in science and healthcare but use only a tiny fraction of their potential. No more than ≈10 p.p.

Involvement of right STS in audio-visual integration for affective speech demonstrated using MEG.

Speech and emotion perception are dynamic processes in which it may be optimal to integrate synchronous signals emitted from different sources. Studies of audio-visual (AV) perception of neutrally expressed speech demonstrate supra-additive (i.e.

Oscillatory neuronal dynamics associated with manual acupuncture: a magnetoencephalography study using beamforming analysis.

Magnetoencephalography (MEG) enables non-invasive recording of neuronal activity, with reconstruction methods providing estimates of underlying brain source locations and oscillatory dynamics from externally recorded neuromagnetic fields. The aim of our study was to use MEG to determine the effect of manual acupuncture on neuronal oscillatory dynamics. A major problem in MEG investigations of manual acupuncture is the absence of onset times for each needle manipulation.

A robust implementation of a kurtosis beamformer for the accurate identification of epileptogenic foci.

Objective: To improve the accuracy and reliability of the localisation of epileptogenic activity using spatially filtered MEG data.

Methods: A synthetic epileptic source was embedded in healthy brain activity in different orientations in order to estimate how reliably this signal containing high levels of kurtosis can be localised. An existing approach (SAM(g2)) was compared to a new implementation of the methodology.

Representations of the temporal envelope of sounds in human auditory cortex: can the results from invasive intracortical "depth" electrode recordings be replicated using non-invasive MEG "virtual electrodes"?

Magnetoencephalography (MEG) beamformer analyses use spatial filters to estimate neuronal activity underlying the magnetic fields measured by the MEG sensors. MEG "virtual electrodes" are the outputs of beamformer spatial filters. The present study aimed to test the hypothesis that MEG virtual electrodes can replicate the findings from intracortical "depth" electrode studies relevant to the processing of the temporal envelopes of sounds [e.

Utilization of SABRE-derived hyperpolarization to detect low-concentration analytes via 1D and 2D NMR methods.

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements.

Stimulus variability affects the amplitude of the auditory steady-state response.

In this study we investigate whether stimulus variability affects the auditory steady-state response (ASSR). We present cosinusoidal AM pulses as stimuli where we are able to manipulate waveform shape independently of the fixed repetition rate of 4 Hz. We either present sounds in which the waveform shape, the pulse-width, is fixed throughout the presentation or where it varies pseudo-randomly.

Estimation of functional connectivity from electromagnetic signals and the amount of empirical data required.

An increasing number of neuroimaging studies are concerned with the identification of interactions or statistical dependencies between brain areas. Dependencies between the activities of different brain regions can be quantified with functional connectivity measures such as the cross-correlation coefficient. An important factor limiting the accuracy of such measures is the amount of empirical data available.

Cross-channel amplitude sweeps are crucial to speech intelligibility.

Classical views of speech perception argue that the static and dynamic characteristics of spectral energy peaks (formants) are the acoustic features that underpin phoneme recognition. Here we use representations where the amplitude modulations of sub-band filtered speech are described, precisely, in terms of co-sinusoidal pulses. These pulses are parameterised in terms of their amplitude, duration and position in time across a large number of spectral channels.

Time scales of representation in the human brain: weighing past information to predict future events.

The estimates that humans make of statistical dependencies in the environment and therefore their representation of uncertainty crucially depend on the integration of data over time. As such, the extent to which past events are used to represent uncertainty has been postulated to vary over the cortex. For example, primary visual cortex responds to rapid perturbations in the environment, while frontal cortices involved in executive control encode the longer term contexts within which these perturbations occur.

Iridium N-heterocyclic carbene complexes as efficient catalysts for magnetization transfer from para-hydrogen.

While the characterization of materials by NMR is hugely important in the physical and biological sciences, it also plays a vital role in medical imaging. This success is all the more impressive because of the inherently low sensitivity of the method. We establish here that [Ir(H)(2)(IMes)(py)(3)]Cl undergoes both pyridine (py) loss as well as the reductive elimination of H(2).