CIBM MRI EPFL SECTION

Animal Imaging and Technology

Section Head: Prof. Rolf Gruetter (EPFL)

The CIBM MRI EPFL Animal Imaging and Technology Section activities center on 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, a 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

Method development for rodent functional MRI at 9.4T and 14T

Description: We develop specific tools and methods for rodent fMRI at 9.4 and 14T including, but not limited to:

  • Robust and comprehensive processing pipelines for functional connectivity of the rat brain
  • Acquisition schemes for distortion-free fMRI images
  • Optimized anesthesia protocols for minimal impact on functional response
  • Diffusion functional MRI contrast that does not rely on neurovascular coupling, for improved specificity to neural activity

Investigators: Ileana Jelescu, Ting Yin (EPFL)

Functional characterization of neural circuits linked to fear and anxiety

Description: We use resting-state functional MRI to study the whole brain functional connectivity for naive and basolateral amygdala silenced animals after active avoidance learning.
Combining optogenetic stimulation and functional MRI, we aim to study the projections from oxytocin producing neurons in the hypothalamic paraventricular, and to investigate the potential of using MRI compatible optical electrode for simultaneously electrophysiological recordings.

Investigators: Ting Yin (EPFL), Ileana Jelescu (EPFL)

Collaborators: Prof. Ron Stoop (CHUV), Rodrigo Triana-Del Río (NYU)

Intravoxel incoherent motion diffusion weighted imaging of human pancreas

Description: We develop batch processing pipeline for clinical DWI data, which includes data quality assessment, motion correction for free-breathing abdominal DWI, denoising, and quantitative analysis of IVIM model in the pancreas from healthy subjects and patients with pancreatic adenocarcinomas. Meanwhile, we investigate the scan-rescan reproducibility of IVIM parameters.

Investigator: Ting Yin (EPFL)

Collaborators: Chao Ma (Changhai Hospital of Shanghai, P.R.China)

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)

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)

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

Description: 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 animal models of schizophrenia and 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: Prof. Kim Q Do (Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV), Prof. Philippe Conus (Service of General Psychiatry, Department of Psychiatry, CHUV) and Radek Skupienski (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: Sandra Da Costa (EPFL)

Collaborators: Drs G. Wuerzener and M. Hendriks-Balk (Nephrology, CHUV)

Functional investigation of the human auditory cortex at 7T in healthy subjects with/without hearing deficits

Description: Hearing deficits such as hearing loss and tinnitus are present in more than 10 % of the worldwide population, a prevalence increasing up to 40% in adults older than 65 years old. These impairments influence auditory perception, inducing long-term effects such as difficulties in speech understanding in noisy or reverberant environments which, if not treated, contribute to isolation, cognitive impairments, depression and dementia. These sensory and cognitive deficiencies are correlated with the reorganization within specific auditory areas, but also, at a broader range, with restructuration of larger networks. The scope of this project is: first, to optimize actual imaging sequences, developed at the CIBM, to improve the localization and parcellation of the human auditory cortex using cytoarchitectonic landmarks and functional properties; second, to apply these sequences to investigate and quantify the reorganisation of the auditory cortex in hearing impaired subjects, while the subjects are performing either passive listening or an auditory active task. Altogether, these aims will allow a better understanding of how hearing deficits shape the brain and induce cognitive impairments, but also how selective attention might be a resourceful tool for developing rehabilitation techniques helping people with hearing deficits.

Investigator: Sandra Da Costa (EPFL)

Collaborator: Dr Raphael Maire (ORL, CHUV)

Evaluation of the whole auditory pathway using high-resolution and functional MRI at 7T parallel-transmit

Description: The purpose of this project is to develop a time-efficient MR procedure for the evaluation of auditory functions, integrating high-resolution structural and functional MRI, using parallel-transmit methods at 7T. RF weights were optimized for the regions-of-interest and high-resolution MR images of the inner-ear were acquired. Then in a second part, functional MRI acquisitions along the whole auditory pathway were acquired to evaluate the functional organisation of the auditory pathway, in small regions of interest such as the inferior colliculus or the mediate geniculate gyrus but also up to the auditory cortex. This MR procedure provide a fast and qualitative evaluation of the auditory response and anatomical images of the inner-ear in less than 60 min at 7T.

Investigator: Sandra Da Costa (EPFL)

Collaborators: Jérémie Clément and Ozlem Ipek (King’s College, London)

Disrupted brain glucose metabolism in taking center stage, in the search for an initial trigger of Alzheimer's disease.

Description: A longitudinal study of a rat model of sporadic Alzheimer’s disease based on an intracerebroventricular injection of streptozotocin is being investigated by measuring brain glucose metabolism at four timepoints (2, 6, 13, 21 weeks post-injection) using FDG-PET, as well as changes in brain microstructure and function using diffusion and functional MRI, respectively.

Investigator: Ileana Jelescu (EPFL)

Collaborators: Bernard Lanz (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)

Collaborator: Bernard Lanz (EPFL)

Neurometabolism in Chronic Hepatic Encephalopathy

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)

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

Fast Spectroscopic Imaging in rodent brain

Description: MR spectroscopic imaging (MRSI) is a powerful tool to non-invasively map brain metabolites in animals and humans, 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 fast and highly spatially resolved MRSI of the whole rodent brain combined with an automatic processing pipeline for phase/frequency corrections and automatic quality control. 

Investigator: Cristina Cudalbu (EPFL)

Collaborator: Wolfgang Bogner (Medical University of Vienna, Austria)

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), Ileana Jelescu (EPFL)

Collaborators: Julien Valette (CEA Paris), Roland Kreis (University of Bern)