Measurement of the Mapping between Intracranial EEG and fMRI Recordings in the Human Brain.

There are considerable gaps in our understanding of the relationship between human brain activity measured at different temporal and spatial scales. Here, electrocorticography (ECoG) measures were used to predict functional MRI changes in the sensorimotor cortex in two brain states: at rest and during motor performance. The specificity of this relationship to spatial co-localisation of the two signals was also investigated.

Visualisation of drug distribution in skin using correlative optical spectroscopy and mass spectrometry imaging.

A correlative methodology for label-free chemical imaging of soft tissue has been developed, combining non-linear optical spectroscopies and mass spectrometry to achieve sub-micron spatial resolution and critically improved drug detection sensitivity. The approach was applied to visualise the kinetics of drug reservoir formation within human skin following in vitro topical treatment with a commercial diclofenac gel. Non-destructive optical spectroscopic techniques, namely stimulated Raman scattering, second harmonic generation and two photon fluorescence microscopies, were used to provide chemical and structural contrast.

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues.

A Multimodal Desorption Electrospray Ionisation Workflow Enabling Visualisation of Lipids and Biologically Relevant Elements in a Single Tissue Section.

The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative and infectious diseases and are known to disrupt lipid metabolism. Desorption electrospray ionisation (DESI) is a widely used approach for molecular imaging, but previous work has shown that DESI delocalises ions such as potassium (K) and chlorine (Cl), precluding the subsequent elemental analysis of the same section of tissue.

Exploring New Methods to Study and Moderate Proton Beam Damage for Multimodal Imaging on a Single Tissue Section.

Characterizing proton beam damage in biological materials is of interest to enable the integration of proton microprobe elemental mapping techniques with other imaging modalities. It is also of relevance to obtain a deeper understanding of mechanical damage to lipids in tissues during proton beam cancer therapy. We have developed a novel strategy to characterize proton beam damage to lipids in biological tissues based on mass spectrometry imaging.

Implications of Peak Selection in the Interpretation of Unsupervised Mass Spectrometry Imaging Data Analyses.

Mass spectrometry imaging can produce large amounts of complex spectral and spatial data. Such data sets are often analyzed with unsupervised machine learning approaches, which aim at reducing their complexity and facilitating their interpretation. However, choices made during data processing can impact the overall interpretation of these analyses.

Direct Tissue Mass Spectrometry Imaging by Atmospheric Pressure UV-Laser Desorption Plasma Postionization.

Matrix-assisted laser desorption ionization (MALDI) operated at atmospheric pressure has been shown to be a promising technique for mass spectrometry imaging of biological tissues at high spatial resolution. Recent studies have shown several orders of magnitude improvement in sensitivity afforded by coupling with a low-temperature plasma (LTP) for postionization. In this work we report the first results from "matrix-free" imaging using our atmospheric pressure (AP) transmission mode (TM) (MA)LDI source with LTP postionization.

MALDI-2 at Atmospheric Pressure-Parameter Optimization and First Imaging Experiments.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful label-free technique for mapping the spatial distribution of biomolecules directly from tissue. However, like most other MSI techniques, it suffers from low ionization yields and ion suppression effects for biomolecules that might be of interest for a specific application at hand. Recently, a form of laser postionization was introduced (coined MALDI-2) that critically boosts the ion yield for many glyco- and phospholipids by several orders of magnitude and makes the detection of further biomolecular species possible.

Construction and testing of an atmospheric-pressure transmission-mode matrix assisted laser desorption ionisation mass spectrometry imaging ion source with plasma ionisation enhancement.

Matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) at atmospheric pressure (AP) is, with a few notable exceptions, overshadowed by its vacuum based forms and AP transmission mode (TM) MALDI-MS lacks the up-take its potential benefits might suggest. The reasons for this are not fully understood and it is clear further development is required to realise the flexibility and power of this ionisation method and geometry. Here we report the build of a new AP-TM-MALDI-MSI ion source with plasma ionisation enhancement.

BOLD mapping of human epileptic spikes recorded during simultaneous intracranial EEG-fMRI: The impact of automated spike classification.

Objectives: Simultaneous intracranial EEG and functional MRI (icEEG-fMRI) can be used to map the haemodynamic (BOLD) changes associated with the generation of IEDs. Unlike scalp EEG-fMRI, in most patients who undergo icEEG-fMRI, IEDs recorded intracranially are numerous and show variability in terms of field amplitude and morphology. Therefore, visual marking can be highly subjective and time consuming.

A novel scheme for the validation of an automated classification method for epileptic spikes by comparison with multiple observers.

Objective: To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data.

Method: Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs.

Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions.

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in 'healthy' non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI.

Phase-amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task.

Although it has been consistently found that local blood-oxygen-level-dependent (BOLD) changes are better modelled by a combination of the power of multiple EEG frequency bands rather than by the power of a unique band alone, the local electro-haemodynamic coupling function is not yet fully characterised. Electrophysiological studies have revealed that the strength of the coupling between the phase of low- and the amplitude of high- frequency EEG activities (phase-amplitude coupling - PAC) has an important role in brain function in general, and in preparation and execution of movement in particular. Using electrocorticographic (ECoG) and functional magnetic resonance imaging (fMRI) data recorded simultaneously in humans performing a finger-tapping task, we investigated the single-trial relationship between the amplitude of the BOLD signal and the strength of PAC and the power of α, β, and γ bands, at a local level.

A study of the electro-haemodynamic coupling using simultaneously acquired intracranial EEG and fMRI data in humans.

In current fMRI studies designed to map BOLD changes related to interictal epileptiform discharges (IED), which are recorded on simultaneous EEG, the information contained in the morphology and field extent of the EEG events is exclusively used for their classification. Usually, a BOLD predictor based on IED onset times alone is constructed, effectively treating all events as identical. We used intracranial EEG (icEEG)-fMRI data simultaneously recorded in humans to investigate the effect of including any of the features: amplitude, width (duration), slope of the rising phase, energy (area under the curve), or spatial field extent (number of contacts over which the sharp wave was observed) of the fast wave of the IED (the sharp wave), into the BOLD model, to better understand the neurophysiological origin of sharp wave-related BOLD changes, in the immediate vicinity of the recording contacts.

Characterisation and reduction of the EEG artefact caused by the helium cooling pump in the MR environment: validation in epilepsy patient data.

The EEG acquired simultaneously with fMRI is distorted by a number of artefacts related to the presence of strong magnetic fields, which must be reduced in order to allow for a useful interpretation and quantification of the EEG data. For the two most prominent artefacts, associated with magnetic field gradient switching and the heart beat, reduction methods have been developed and applied successfully. However, a number of artefacts related to the MR-environment can be found to distort the EEG data acquired even without ongoing fMRI acquisition.

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG-fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG.

Dynamic Causal Modelling of epileptic seizure propagation pathways: a combined EEG-fMRI study.

Simultaneous EEG-fMRI offers the possibility of non-invasively studying the spatiotemporal dynamics of epileptic activity propagation from the focus towards an extended brain network, through the identification of the haemodynamic correlates of ictal electrical discharges. In epilepsy associated with hypothalamic hamartomas (HH), seizures are known to originate in the HH but different propagation pathways have been proposed. Here, Dynamic Causal Modelling (DCM) was employed to estimate the seizure propagation pathway from fMRI data recorded in a HH patient, by testing a set of clinically plausible network connectivity models of discharge propagation.