CIBM MRI EPFL SECTION

Animal Imaging and Technology

Interim Section Head: Prof. Dimitri Van de Ville (EPFL)

The activities of the CIBM MRI EPFL Animal Imaging and Technology Section revolve around three Magnetic Resonance systems, namely

  • 9.4 T / 31cm horizontal bore animal MR scanner dedicated to rodent studies with adjacent animal preparation room to ensure good physiology during the scans  with an animal PET scanner in proximity so as to enable multimodal studies on the same rodent.
  • 14 T / 26 cm horizontal bore animal MR scanner (one of four comparable magnets in the world), complemented with a full suite of animal physiology support for anesthesia and surgical preparation, as well as for bench experiments on live rodents.
  • 7 T human MR scanner, dedicated to the brain (world’s first actively-shielded 7T magnet), complemented with a patient suite to accommodate human subject volunteers. Infrastructure available for infusion studies in humans.

These scanners are complemented with the following ancillary infrastructure:

  • Fully equipped RF lab, providing CIBM-wide supporting RF coil infrastructure and electronics support for the entire region.
  • Human volunteer subject preparation room (volunteers and outpatient research subjects) with two beds and space for related interventions.
  • Physiology support for experiments related to animal imaging experimentation providing support for preparation of the rodent, as well as monitoring of physiology to ensure proper physiological parameters during the scan, as well as, compliance with ethical rules.

On-site animal housing facility, managed by EPFL’s center for phenogenomics, and other infrastructure supported by LIFMET, CIBM Affiliate Member, are 

  • Two DNP polarizers (5T at the 14T and 7T at the 9.4T) and associated equipment & lab infrastructure.
  • Neurochemistry lab, providing infrastructure for tissue analysis, related biochemical assays. Infrastructure includes among others, centrifuges and a -80C freezer for sample storage.

Focused microwave fixation device, for rapid deactivation of enzymes.

RESEARCH TOPICS

PRE-CLINICAL

Dynamic 2H MRSI measurement of brain oxidative metabolism

Description:

Deuterium imaging (2H-MRS/MRSI) emerged as a promising in vivo tool to study glucose metabolism by the use of deuterium-labelled substrates. Although research to date has shed some light on the usefulness of deuterium imaging in animal models and humans, current 2H-MRSI acquisitions and reconstructions are often limited to static acquisitions at labelling steady-state.

To enable dynamic measurement of deuterium turnover through the brain oxidative metabolic pathway, our research focuses on implementing accelerated MRSI strategies to 3D 2H-MRSI. All developments are aiming at obtaining dynamic and quantitative 3D images of glucose metabolites 2H turnover, enabling further quantitative determination of cerebral oxidative metabolic rate of glucose CMRglc(ox) through advanced metabolic modelling..

Investigator: Bernard Lanz, Alessio Siviglia, Cristina Cudalbu, Gianna Nossa, Thanh Phong Lê (EPFL).

Collaborators: Bernhard Strasser, Fabian Niess, Wolfgang Bogner (Medical University of Vienna)

Quantitative metabolic mapping of glucose uptake

Description: A novel 18FDG PET-based methodology was developed to quantitate regional cerebral metabolic rate of glucose (CMRglc) in μmol/g/min, using image-derived input function from the vena cava in rodents. This method enables with minimal invasiveness to create 3D metabolic maps of glucose uptake from dynamic PET acquisitions that can be used not only as a quantitative metabolic imaging approach in itself, but can be combined with MRS and MRSI metabolic measurements.
Initially developed on the LabPET4 standalone PET scanner, the approach is currently extended to be used on the newly installed PET-MR equipment of the preclinical 9.4T scanner and for metabolic imaging in various organs.

Investigator: Bernard Lanz (EPFL), Omar Zenteno (EPFL).

Collaborators: Volumina Medical SA

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In vivo brain metabolism and it’s regional differences in disease by 1H MRS

Description: Chronic hepatic encephalopathy (chronic HE) is a neurological disease caused by chronic liver disease (CLD). Unlike adults, children grow up with significant neurological deficits even after liver transplantation, suggesting that the immature brain is uniquely vulnerable to the insults associated with CLD.
Despite considerable advances in understanding the pathogenesis of many neurological diseases, key questions remain unanswered for chronic HE. What makes the developing brain more vulnerable? What regional brain metabolic changes occur in response to elevated ammonium and its metabolic product glutamine (Gln)? How do these affect the morphology and function of brain cells?
Current therapies aimed at lowering peripheral ammonium load are insufficient to avoid long-term clinical consequences in children. Therefore, identifying novel molecular pathways involved in chronic HE that might be amenable to therapeutic intervention would be a major advance.
The current project aims to address the molecular, regional, and age-dependence changes in chronic HE in vivo and longitudinally using a multi-modal approach based on dynamic multinuclear MRS(I) and MRI at ultra-high filed, PET and ex-vivo histological measures in the adult and developing brain under chronic HE.

Investigator: Cristina Cudalbu (EPFL), Bernard Lanz (EPFL), Thanh Phong Lê (EPFL), Katarzyna Pierzchala (EPFL), Brayan Alves (EPFL), Gianna Nossa (EPFL).

Collaborators: Olivier Braissant (CHUV, UNIL), Valerie McLin (HUG UNIGE)

Hardware and method development for preclinical MR

Description: We develop custom tools and methods for preclinical MR at 9.4T and 14.1T, for example:

  • Design, electromagnetic simulations and manufacturing of single- and multi-tuned radiofrequency coils.
  • Development of acquisition sequences and processing pipelines for MR spectroscopic imaging.
  • Animal and phantom fixation apparatus tailored to specific experimental requirements.
  • Ancillary devices for MR experiments, such as stimulation interfaces for functional MR, animal physiological support and monitoring system, fluidic pumps, …

Investigator: Thanh Phong Lê (EPFL), Cristina Cudalbu (EPFL), Bernard Lanz (EPFL) 

Fast high-resolution metabolic imaging in the brain at ultra-high magnetic field

Description:

MR spectroscopic imaging (MRSI) is a powerful tool that enables the simultaneous noninvasive acquisition of MR spectra from multiple spatial locations inside the brain, with one drawback the long measurement times.

Several methods have been proposed to accelerate 1H MRSI UHF for clinical applications (i.e. FID-MRSI and spatial-spectral encoding), with in plane spatial resolutions of 1.7-10 mm and the detection of several metabolites.

High resolution 1H MRSI preclinical data quantitatively mapping an extended number of metabolites are still acquired using traditional phase encode MRSI, as pioneered by our group, while 31P MRSI in preclinical models is non-existent.

MRSI is highly challenging due to metabolites low concentration, long measurement times, signal-to-noise ratio (SNR), hardware limitations (B0 and gradients strength, RF coils, B0 inhomogeneities), advanced pulse sequences and processing that need to be developed in-house, quality assessment of a huge number of spectra, and precision and reliability of derived metabolite maps.

The main goal is therefore to develop 3D fast and highly spatially resolved MRSI of the whole rodent brain combined with an automatic processing pipeline and automatic quality control. 

Investigator: Cristina Cudalbu (EPFL), Thanh Phong Lê (EPFL), Brayan Alves (EPFL), Gianna Nossa (EPFL), Tan Toi Phan (EPFL)

Collaborators: Bernard Lanz (EPFL), Bernhard Strasser (Medical University of Vienna), Wolfgang Bogner (Medical University of Vienna)

Diffusion weighted spectroscopy

Description: Diffusion-weighted MRS (DW-MRS) probes metabolites diffusion properties which are expected to reflect properties of intracellular space (i.e. cell type geometry, structure, cytosol viscosity, molecular crowding). Unlike water, metabolites probe the intracellular space only and some are considered to be partially specific to glial (Gln, Ins) or neuronal (NAA and Glu) cells, while others are found in all cell types (tCr).

Brain metabolite compartmentation has been little studied by DW-MRS because of the complexity of the technique and the difficulties of modeling the spectra (i.e. intracellular diffusion). However, some recent advances proposed that high diffusion-weighting MRS data reflect the radius of brain cell fibers (dendrites, axons, astrocytic processes), data from long diffusion times reflect long-range fiber structure (complexity and length), while diffusion of metabolites in brain cells can be modelled as long hollow cylinders for diffusion times <100 ms.

We will exploit these advances to use DW-MRS of Gln in vivo to probe astrocyte morphology and size in healthy and diseased rodent brain at ultra-high field. 

Investigator: Cristina Cudalbu (EPFL)

Collaborators: Julien Valette (CEA Paris), Roland Kreis (University of Bern), Ileana Jelescu (EPFL), Katarzyna Pierzchala (EPFL)

PhD students : Dunja Simicic, Jessie Mosso (EPFL)

Dynamic X-nuclei MRS in the rodent brain in vivo

Description: MRS is the only technique capable of measuring a large number of metabolites simultaneously in vivo. 1H MRS allows the direct detection of 19 metabolites, comprising markers of energy metabolism, osmoregulation, myelination/cell proliferation, neurotransmitters and antioxidants.

31P MRS provides complementary information about energy transfer molecules (ATP), antioxidants (NAD+/NADH), chemical reaction rates (creatine kinase, ATP synthase), cell membrane metabolites and also calculation of additional important physiological parameters (intracellular pH and Mg2+, ADP concentration).

13C MRS combined with labelled substrates allows the non-invasive study of metabolite fluxes through the tricarboxylic acid cycle (TCA) and glutamate-glutamine cycle in vivo. 15N MRS is an alternative approach to 13C MRS to study glutamate-glutamine metabolism.

We aim at developing new interleaved dynamic direct and indirect acquisition sequences for X-nuclei MRS(I) combined with metabolic modelling using a novel approach extended by the incorporation of prior knowledge from multimodal acquisitions for the measurement of energy metabolism in healthy and diseased rodent brain in vivo.

Investigator: Cristina Cudalbu (EPFL)

Collaborators: Bernard Lanz, Katarzyna Pierzchala (EPFL) 

PhD students : Dunja Simicic, Jessie Mosso (EPFL)

Microstructural MRI

Description: In a diffusion MRI experiment, water molecules in the brain diffuse over a few microns – a distance on the same order as major microstructural features of the tissue – and their mobility is largely governed by restrictions and hindrances related to the tissue architecture. In other words, the diffusion MRI signal encodes information about length scales much smaller than the actual spatial resolution of the MR image, and thus about features of the underlying tissue microstructure that we otherwise cannot spatially resolve in vivo. The main goal of Microstructural MRI is therefore to develop and validate biophysical models that decode the diffusion MRI signal in terms of quantitative estimates of specific features of white and gray matter microstructure in vivo and non-invasively. These metrics have high potential as sensitive and specific biomarkers of neurodegeneration in a variety of conditions. Example projects include microstructural characterization of brain changes in dementia, stroke, autism spectrum disorder, hypofrontality, etc. 

Investigator: Ileana Jelescu (EPFL)

Collaborators: Giovanni Frisoni (HUG), Grégoire Courtine (EPFL) and Jocelyne Bloch (CHUV), Prof. Claudia Bagni (UNIL), Prof. Benjamin Boutrel (UNIL), Prof. Jean-Philippe Thiran (EPFL)

7Tesla MRI

RF Lab - Development of radio frequency technology for ultra-high field MRI

Description: The research focuses on the development of hardware solutions and clinical applications for ultrahigh field magnetic resonance imaging (UHF-MRI) and magnetic resonance spectroscopy (MRS). We develop new, multi-channel, single- and multi-tuned RF transmit/receive and receive-only coils, which provide more efficient RF power transmission and higher signal-to-noise ratio, and thus enabling faster MRI scans and higher spatial resolution of the acquired MR images. In this research, we use different tools to design, optimize, build and evaluate RF coils/antennas and RF components: electromagnetic field and specific absorption rate simulations, RF field optimization algorithms, RF circuit simulations, 3D mechanical design software, and everything that can be found in a well-equipped RF laboratory.

Investigator: Daniel Wenz (EPFL)

Development of multi-channel loop-dipole antenna arrays for MRI at 7.0 Tesla

Description: The aim of this project is to enhance signal-to-noise ratio (SNR) in ultrahigh field MRI at 7.0 Tesla, by developing a new generation of high channel-count, low loss, loop-dipole arrays which would enable achieving ultimate intrinsic SNR at ultrahigh field MRI and MR spectroscopy.

Investigator: Daniel Wenz (EPFL)

Collaborator: Lijing Xin (EPFL)

Development of optimal, multi-channel array combination of dielectric resonators and dipole antennas for MR spectroscopy at 7.0 Tesla

Description: Dielectric resonators are an interesting alternative to conventional loop elements, especially at ultrahigh magnetic field strengths. The properties of dielectric materials can be easily modified, what provides an extra degree of freedom for the development of new, application-oriented RF antennas. The goal of this project is to develop and optimize a multi-channel combination of dielectric resonators and dipole antennas, and explore its advantages for MRI at magnetic field strengths higher than 7.0 Tesla.

Investigator: Daniel Wenz (EPFL)

Novel hardware technologies for neuroimaging and neurostimulation

Description: 

High receive sensitivity is the holy grail of every magnetic resonance imaging (MRI) study. In our research, we aim to substantially boost receive sensitivity in different neuroimaging applications, accelerating total scan time and increasing spatial resolution.  We develop innovative hardware concepts for the next generation of MRI detectors, particularly suitable for ultra-high field (UHF) MRI (B0 ≥ 7 T), focusing on unconventional transmit and receive radio frequency (RF) coil arrays involving strategies such as dipole antennas, dielectric resonators, and flexible loop coils. In addition, we explore new solutions for advanced, MRI-based techniques that can provide unique insights into the metabolism and function of the brain, such as phosphorus (31P) MR spectroscopy and electroencephalography combined with functional MRI (EEG/fMRI). Furthermore, we are working on highly promising, non-invasive human brain stimulation strategies. In particular, we develop hybrid hardware systems enabling transcranial low-intensity focused ultrasound (LIFU) neuromodulation combined with UHF-MRI, aiming at finding new ways to treat neurological and neuropsychiatric diseases.

INVESTIGATORS: Daniel Wenz (EPFL)

COLLABORATORS: Rares Salomir (HUG), Jean-Paul Vallee (HUG), Lijing Xin (EPFL), Irena Zivkovic (TU Eindhoven, The Netherlands)

Fast metabolic imaging by magnetic resonance spectroscopic imaging

Description: Whole-brain proton magnetic resonance spectroscopic imaging (1H-MRSI) is a non-invasive technique for assessing neurochemical distribution in the brain, offering valuable insights into brain functions and neural diseases. It greatly benefits from the improved SNR at ultrahigh field strengths. However, 1H-MRSI still faces challenges, such as long acquisition time and signal contamination from water and lipids. In this project, we develop 2D and 3D short TR/TE 1H-FID-MRSI sequences using rosette trajectories with high spatial resolution for mapping brain metabolites including N-Acetyle-L-aspartic acid (NAA), Glutamate (Glu), total choline, Creatine and Phosphocreatine (tCr), and Glycine and myo-Inositol (Gly+Ins)..

Investigator: Lijing Xin (EPFL)

Collaborators: Uzay Emir (UNC, USA),  Zhi-Pei Liang (UIUC, USA)

The neurometabolic connectome: a new window on brain disease

Description:Magnetic resonance spectroscopy is a unique non-invasive technique to measure a variety of brain metabolites (e.g., N-acetylaspartate, creatines, choline, inositol) and certain neurotransmitters (glutamate, Gamma-Aminobutyric Acid). However, so far it has remained mostly a single voxel technique with limited spatial and temporal resolution. By leveraging novel MR sequence designs (edited MRSI), spatial encoding schemes (rosette trajectory), and reconstruction methods (compressed sensing) on a state-of-the-art 7T Terra.X MR scanner the aim of this project is to improve spatial and temporal resolution to establish functional MR spectroscopic imaging (fMRSI) that enables the measurement of modulation patterns of neurotransmitter concentrations upon stimulation in the human brain, and the mapping of brain metabolic connectivity.

Investigator: Lijing Xin (EPFL), Andre Doring (EPFL)

Collaborators: Uzay Emir (UNC, USA), Zhi-Pei Liang (UIUC, USA), Dimitri Van de Ville (EPFL)

Method development for X-nuclei magnetic resonance spectroscopy

Description: X-nuclei magnetic resonance spectroscopy (MRS) allows non-invasive measurement of neurochemical, metabolic and physiological events in the living brain. The increase in sensitivity and resolution is currently driving the use of ultra-high magnetic field scanners.  However, to fully exploit these advantages of an ultra-high field human scanner necessitates the development first of advanced methodologies. Especially, the X- nuclei MRS functionality of clinical scanners is still far behind magnetic resonance imaging techniques and that on preclinical scanners, due to the need to overcome multiple technical challenges. Therefore, we focus on surmounting the technical issues, developing new X-nuclei MRS methods and advancing their capability for human MR scanner at high magnetic field. Currently our focuses are the metabolic fluxes (TCA cycle metabolism and ATP metabolism) measurement using dynamic 13C MRS, 31P MRS, MRSI and MR fingerprinting.

Investigator: Lijing Xin (EPFL)

Collaborators: Bernard Lanz (EPFL), Uzay Emir (UNC, USA), Yun Jiang (Department of Radiology, University of Michigan, USA), Xin Yu (Department of Biomedical Engineering, Case Western Reserve University, Cleveland, USA)

Functional magnetic resonance spectroscopy: targeting neurometabolic alterations underlying cognition

Description: Functional MRS (fMRS) allows us to monitor the metabolites dynamics from rest to neuronal activation. Increases in some metabolites, i.e. lactate and glutamate (one major neurotransmitter), were observed in response to neuronal activation in these tasks. These changes reflect a response to stimulated energy metabolism upon neuronal activation, offering insights into how brain neurogenetics is regulated to support these sensory tasks. Cognitive deficits have been consistently shown in aging, many psychiatric disorders, and neurodegenerative diseases such as mild cognitive impairment, Parkinson disease and Alzheimer’s disease. Therefore, the investigation of the underlying neurometabolic mechanism during a cognitive task by fMRS is of great interest.  We aim to use fMRS to investigate metabolic dynamics underlying cognition and explore the link between cognitive aspects and the functional neurochemical characteristics.

Investigator: Lijing Xin (EPFL), Antonia Kaiser (EPFL)

Collaborators: Ines Khadimallah (Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV)

Promoting the modulatory capacity of intracortical inhibition in young and old: interrelation of physical exercise and sleep

The human cortical inhibitory system is known to play a crucial role for normal brain development, function and plasticity thereby acting on both, cognitive and motor processes. Furthermore, cortical inhibition is crucial for sleep induction and sleep maintenance. The principal inhibitory neurotransmitter in the central nervous system is gamma-aminobutyric acid (GABA). The general amount of GABAergic inhibition is crucial with respect to motor control and motor learning but rather the capacity to task- and phase-specifically modulate GABA release, i.e. the modulatory range. Furthermore, modulation of GABA release is also vital for sleep induction and sleep maintenance. The aim of the current study is to investigate the close reciprocal interrelation of physical activity and sleep on the mechanistic and behavioral level. This could be of great significance as there is growing recognition of the importance of sleep to improve population health due to the convincing evidence linking sleep to a range of health outcomes.

Investigator: Lijing Xin (EPFL), Wolfgang Taube (University of Fribourg)

Collaborators: Benedikt Lauber (University of Fribourg)

Method development for multinuclear (1H, 13C and 31P) magnetic resonance spectroscopy

Description: Multinuclear magnetic resonance spectroscopy (MRS) using 1H, 13C and 31P nuclei allows non-invasive measurement of neurochemical, metabolic and physiological events in the living brain. The increase in sensitivity and resolution is currently driving the use of ultra-high magnetic field scanners.  However, to fully exploit these advantages of an ultra-high field human scanner necessitates the development first of advanced methodologies. Especially, the multinuclear MRS functionality of clinical scanners is still far behind magnetic resonance imaging techniques and that on preclinical scanners, due to the need to overcome multiple technical challenges. Therefore, we focus on surmounting the technical issues, developing new multinuclear MRS methods and advancing the multinuclear MRS capability for human MR scanner at high magnetic field.

Investigator: Lijing Xin (EPFL)

Collaborators: Yun Jiang (Department of Radiology, University of Michigan, USA), Xin Yu (Department of Biomedical Engineering, Case Western Reserve University, Cleveland, USA)

Biomarkers in psychiatric disorders

Psychiatric disorders are complex neurodevelopmental disorders involving interplay between genetic, developmental and environmental factors. Using advanced 1H, 13C and 31P MRS techniques, we carry on a translational approach in patients with psychosis, for the exploration of potential biomarkers and the identification of molecular mechanisms affecting brain development and regulation that are relevant for the pathophysiology of schizophrenia. The discovery of biomarkers will help us to achieve early diagnose of the disease and ultimately early intervention or even prevention.

Investigator: Lijing Xin (EPFL)

Collaborators: Kim Q Do (UNIL), Prof. Philippe Conus (Service of General Psychiatry, Department of Psychiatry, CHUV),  Ines Khadimallah (Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV), Patric Hagmann (Department of Radiology, CHUV), Paul Klauser (Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV)

Central blood pressure regulation by the brainstem and influence by renal sympathetic afference: a functional magnetic resonance imaging (fMRI) study in hypertensive and normotensive participant

Description: Essential hypertension is a highly prevalent disorder and a major contributor to cardiovascular morbidity and mortality. In hypertension, the overactivity of sympathetic nervous system (SNS) has been found to be implicated in its initiation, maintenance and adverse consequences. The SNS is composed of an afferent and an efferent arm, which respectively bring sensory input information to the brain and then transmits sympathetic outflow from the brain to peripheral organs. It has been shown in animals that selective removal of the afferent renal component of the SNS can modulate central sympathetic outflow to these peripheral organs. In humans, the effect of the afferent component of the SNS on the brain has been difficult to assess so far. In a pilot study in healthy volunteers at 7T, we have shown that a cold pressor test applied to the leg induces a change in BOLD signal intensity in the brainstem. Whether these responses differ in hypertensive patients or whether they can be modulated with renal denervation is unknown. The scope of this project is to evaluate if the brainstem BOLD response to stress is higher in hypertensive patients than in normotensive controls, and that in patients responsive to renal denervation, the BOLD response to stress is decreased compared to non-responders or to non-denervated resistant patients.

Investigator:  (EPFL)

Collaborators:  Grégoire Wuerzener and Murielle Hendriks-Balk (Nephrology, CHUV)