Development of advanced MR imaging methods
Modern state-of-the-art MR scanners make it possible to generate high-resolution images of the brain and body, which allows us to retrieve information about the structure and function of these biological systems. In this project, we are interested in developing advanced MR imaging methods to better probe brain and body, in both healthy and diseased states. By combining a deep knowledge of MR physics with advanced MR hardware and suitable programming skills, our goal is thus to maximize the information, whether of spatial, temporal or spectral nature, that can be extracted from the biological system under study.
Identification and monitoring of microstructural changes with high specificity through in vivo MRI
The diagnosis of brain disorders, attributing one-third of all disease burden, is hindered by the lack of an imaging technique that reveals the architecture of living brain tissue at the cellular resolution of the associated pathological processes by means of biophysically relevant and specific biomarkers. Although the current contrast-driven MR modalities might show sensitivity to those microstructural changes, the lack of specificity limits the diagnostic power of MRI or the usefulness of MRI as a research tool for biological sciences that might fuel our further understanding in disease or aging mechanisms. We focus on the development and validation of MRI as a diagnostic and research tool that allows for the in vivo identification and monitoring of microstructural changes in the unexplored depths of the brain by striving to microstructural specificity of MRI through biophysical modelling of proton diffusion.
Development and validation of advanced diffusion MRI techniques to study brain development and plasticity
Microscopic tissue properties are of special interest in biology as many cellular and sub-cellular structures occur on those scales. However, these properties are beyond the direct resolution limit of contemporary MRI. Fortunately, the characteristic path length of water diffusion in tissues is on the order of microns (given MR-relevant timescales), making diffusion MRI (dMRI) one of the most valuable reporters for dimensions much smaller than the MRI voxel size in both health and disease. Our research interest is to develop and validate advanced dMRI techniques. Our aim is to identify the benefits and pitfalls of dMRI techniques and illustrate their applicability to study brain development and plasticity. We are also interested on the translation of dMRI techniques to characterise neurological pathologies and the progression of tumours.
Learning and rehabilitation-induced microstructural changes revealed by diffusion-weighted MRI
Neuroplasticity refers to the brain’s potential to reorganize structural and functionally in response to learning and experience. Animal models suggest the existence of a sensitive period (SP) of heightened plasticity immediately after stroke, with obvious similarities with developmental critical periods, and characterised by increased responsiveness to training. Despite the existing behavioural evidence of such effect in rodents performing a motor prehension task, the mechanisms underlying neuroplastic phenomena remain largely unknown. In this project, we aim to implement ultrahigh field magnetic resonance (MR) techniques, namely diffusion-weighted MR, to track in vivo the microstructural changes of mice learning in healthy condition and rehabilitating from stroke, while using quantitative kinematics from video recordings to monitor the underlying behavioural evolution in a motor prehension task. Our ultimate goal is to unravel aspects of neuronal reorganization, fundamental for paving the way towards understanding neuroplastic mechanisms.
Functional MRI of the rodent visual pathway with stable and recoverable sedation
We are interested in the investigation of the rodent visual pathway by combining high-field BOLD fMRI with emerging anaesthetic protocols that provide stable and recoverable sedation without compromising the neurovascular coupling. We aim to develop a system that enables the delivery of accurate and complex visual stimuli inside the MRI scanner and therefore the study of different properties in the entire pathway, such as motion, orientation, direction or even shape dependence. Moreover, we focus on the development and validation of anaesthetic protocols and experimental setups that allow longer scanning periods and maintenance of normal animal physiology throughout the fMRI experiment.
Functional MR spectroscopy to study brain metabolism under activation
Magnetic resonance spectroscopy (MRS) is a potential powerful tool to study brain metabolism in resting state (to characterize a pathology for example) or upon activation to possibly quantify the variation of main neurotransmitters (Glu, GABA). Functional MRS (fMRS) is challenging and there is still a lot to do to understand the measure itself, to reach its most relevant interpretation. This work aims at exploring fMRS, using different filters and combining it with functional imaging, to better characterize and understand activation in the brain under various stimuli.
Neurotransmitter quantification through overlap-resolved CEST
Chemical Exchange Saturation Transfer (CEST) can provide metabolic imaging at high spatial resolution, especially at ultrahigh fields. However, when spectral overlap exists downfield, metabolite maps may be contaminated by other unwanted signals. We developed a new methodology termed overlap-resolved CEST (orCEST), which, through subtraction in CESTasym spectra, provides enhanced specificity capable of imaging and quantifying in a consistent, easy, and reliable way the major excitatory and inhibitory neurotransmitters in the brain, Glutamate and GABA.
Diffusion fMRI using brain slices
Despite its immense utility in mapping brain function, MRI’s main functional contrast – the Blood-Oxygenation-Level-Dependent (BOLD) mechanism is an indirect marker of neural activity and its underlying neurovascular coupling mechanisms remain poorly understood. Diffusion functional MRI (dfMRI) has been proposed as a more direct method for detecting neural activity with faster dynamics and with more spatial specificity compared to BOLD. However, much controversy surrounds dfMRI, mainly due to potential BOLD contamination. This project aims to validate dfMRI using brain slices, where vascular responses are absent and where pharmacology can be used to modulate neuronal/vascular responses. As well, those slices can be used to tune and optimize dfMRI contrasts.
Functional MRI and calcium readout of locus coeruleus optogenetic activation
This research project aims at a better understanding of the physiological phenomena underlying functional MRI. To this end, we combine fMRI with optogenetic stimulation and optical calcium recordings inside the scanner. In particular, we are interested in a small brainstem nucleus called locus coeruleus (LC). LC has connections to almost every region in the forebrain and regulates vital autonomous and cognitive functions – it helps us to stay awake when sleeping would be dangerous, to focus our attention on the most critical events in our environment and to store them in memory. LC is also one of the first structures to degenerate in Alzheimer’s and Parkinson’s disease. Through optogenetic stimulation of LC, and the combined fMRI and calcium readout, we investigate the system-level effects through which LC achieves its broad downstream effects.
Diffusion-weighted contrast for fMRI coupled with electrophysiology and optogenetics
In this project, we are focused in studying the differences between BOLD and diffusion-weighted (dfMRI) signals for functional MRI. Using the forepaw stimulation model in rodents, we have been able to demonstrate that dfMRI signals provide a much more detailed information about the circuitry of the thalamo-cortical pathway in forelimb sensation. To better understand the origins of dfMRI contrast in the brain, we are applying cutting-edge MRI techniques combined with electrophysiology and optogenetics.
Whole-brain fMRI of serotonergic neuron optogenetic activation
This project aims to understand where in the brain the neuromodulator serotonin (5-HT) acts to ultimately modulate cognitive and behavioral functions. To this end, we are combining whole-brain imaging using high field (9.4T) functional magnetic resonance imaging (fMRI) with causal optogenetic manipulations in sedated, awake and behaving mice. This way, we aim to map the effects of 5-HT across the brain and use this information to target causal manipulations to specific 5-HT projections.
Characterization of lymph nodes in rectal cancer in preclinical and clinical environments
This project spans both the preclinical and clinical environments. It consists of a new application in magnetic resonance imaging for the distinction between benign and malignant mesorectal lymph nodes in rectal cancer. We first studied individual lymph nodes ex vivo, from the surgical specimens of patients, at 16.4T; and then applied the same methodology in vivo, at 1.5T, upon clinical staging.
Characterising tumour microenvironment
This project focuses on characterising the metabolic and microstructural heterogeneity of the tumour microenvironment and its dynamic changes, in order to establish non-invasive markers of progression and metastasis. This is investigated in preclinical models but with a clear bench-to-bedside perspective, using advanced magnetic resonance imaging and spectroscopy methods.