The research projects
Localyze, a PET-MR study of lymphoma monitoring and therapeutic assessment

Primary central nervous system lymphoma (PCNSL) is a variant of extranodal non-Hodgkin lymphoma (NHL) affecting eyes, brain, leptomeninges, or spinal cord. Ninety percent of non-HIV associated PCNSL cases are of the diffuse large B-cell type (DLBCL). Patients older than 60 years account for half of cases of PCNSL and have a poorer outcome. No prognostic or predictive factors exist for survival after initial remission. FDG PET plays a key role in the grading and therapy monitoring of systemic DLBCL. LOCALYZE (PHRC 2014 Pr Kas) is an ancillary PET/MR study from BLOCAGE 01 (PHRC 2013 Pr Hoang-Xuan).

The aim is to evaluate the usefulness of FDG PET to monitor treatment response in PCNSL older than 60 years (n=56), in complement to MRI. We assume that the development of new imaging biomarker extracted from PET imaging and MRI, could improve the assessment of treatment response in PCNSL.

(Contact: Aurélie Kas, MD,  Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. ; Olivier Jaubert ,MSc , Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

 
2HG Magnetic Resonance Spectroscopy

Non-invasive detection of 2-hydroxyglutarate by MRS in patients with IDH- mutated glioma

The overproduction of the oncometabolite 2-hydroxyglutarate (2HG) in IDH mutated gliomas can be detected non-invasively by magnetic resonance spectroscopy (MRS). Reliable quantification of 2HG has important implications in diagnosis of IDH mutation, prognosis, as well as assessment of the efficacy of conventional and anti-IDH targeted therapies. 2HG detection by MRS is very challenging and advanced methods for robust detection of this metabolite are not available in clinical settings.

We implemented an efficient protocol for reliable detection of 2HG, employing both conventional MR spectroscopy optimized for 2HG detection and difference spectroscopy.

(Contact: Marc Sanson, MD, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. ; Francesca Branzoli, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

 
Diffusion-weighted Magnetic Resonance Spectroscopy projects

Diffusion-weighted magnetic resonance spectroscopy

Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) provides structural and functional information almost exclusively related to the intra-cellular space by probing the diffusion properties of intra-cellular metabolites. In combination with the more sensitive diffusion MRI techniques, DW-MRS allows to disentangle between cell-type specific intra-cellular damage and other pathological processes affecting the extra-cellular space in disease, such as demyelination.

Single-volume diffusion weighted MRS techniques have been implemented and optimized on the 3T Siemens machines at CENIR. We are currently developing new methods for acquisition of DW-MRS data in the spinal cord.

(Contact: Francesca Branzoli, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

Energy disregulation and neuro-axonal dysfunction in multiple sclerosis measured with diffusion-weighted spectroscopy

Energy disregulation is considered a key-contributing factor to neuro-axonal loss in multiple sclerosis (MS). Diffusion-weighted MR spectroscopy (DW-MRS) has the potential to capture in-vivo the ongoing neuro-axonal pathology as well as the potentially reversible phase of energy disregulation which could precede the onset of neuro-axonal degeneration. This technique combines specific measures of neuro-axonal damage, such as the diffusivity of total N-acetilaspartate (tNAA), with measures of cell energy metabolism, such as the diffusivity of total creatine (tCr). We employ DW-MRS to investigate the mismatch between energy demand and supply that could trigger neurodegeneration in conditions of increased energy demand in MS, and to explore the clinical relevance of metabolite diffusion metrics.

(Contact: Benedetta Bodini, MD, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. ; Francesca Branzoli, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

Diffusion Spectroscopy and Imaging in Stroke

Cerebral vascular disorder is one of the most fatal diseases despite current advances in medical science. The large number of negative clinical trials on neuroprotection in acute stroke is a pointer to the fact that translating better understanding of the pathogenesis and pathophysiology to clearly beneficial treatment strategies remains a daunting task. This project aims at elucidating the plausible biophysical events that affect water and metabolite diffusion in brain tissue after ischemia, by combining the information provided by two advanced methods of magnetic resonance (MR) diffusion imaging: diffusional kurtosis imaging and diffusion-weighted spectroscopy.

While diffusion weighted imaging (DWI) has been established as a major tool for the early detection of stroke, the assessment of metabolite diffusion changes by diffusion-weighted MR spectroscopy (DW-MRS) provides information specific to the intracellular environment. In addition, measuring a temporal profile of water and metabolite diffusion may help clarify underlying pathophysiological changes in neuronal cells during acute ischemia.

(Contact: Charlotte Rosso, MD, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. ; Francesca Branzoli, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

 
Maxims

The goal of this project is to investigate axonopathy and myelinopathy in well-established mouse models (leukodystrophy model, multiple sclerosis model and amyotrophic lateral sclerosis model) using diffusion MRI and diffusion-weighted spectroscopy, and to validate MRI biomarkers with multivariate quantitative histological analyses. Biomarkers of axonal and myelin integrity will include MRI metrics that can provide (i) increased specificity to distinct attributes of white matter such as local fiber architecture, axon morphology, myelin content with advanced diffusion-weighted imaging techniques and (ii) new insights into the diffusion properties of intracellular metabolites with diffusion-weighted spectroscopy. More specifically, probing metabolite diffusion at different time scales allows assessing fiber diameter and length, and the specific compartmentalization of different metabolites in different cell types allows differentiating between astrocytic and neuronal microstructural parameters. Although very promising, these novel techniques still need extensive histological validation.

Grant: IHU, 2015 (Contact: Alexandra Petiet, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

 
Study on brain metabolism

'TRIHEP3'

Huntington disease is an autosomal dominant polyglutamine neurodegenerative disease. Many studies point to an energy deficit as one of the contributors to the disease pathophysiology. TRIHEP3 is a blinded, controlled and randomised multicentric study that primarily uses magnetic resonance imaging and spectroscopy (MRS) to evaluate the effect of a drug, triheptanoin, that targets the Krebs cycle. The study uses 31-Phosphorus MRS to evaluate metabolic profiles during brain activation at baseline compared to after treatment with triheptanoin. The boundary shift integral approach is used on 3D volumetric T1-weighted images to evaluate regions of atrophy, particularly, caudate atrophy.

 

'REVHD'

In Huntington disease, the mutant form of the huntingtin protein downregulates important transcription factors such as PGC-1α needed for mitochondrial biogenesis. REV-HD is a blinded, controlled and randomised multicentric study that primarily uses magnetic resonance imaging and spectroscopy (MRS) to evaluate the effect of resveratrol, a compound known to stimulate PGC-1α and improve mitochondrial biogenesis. The study uses 31-Phosphorus MRS to evaluate metabolic profiles during brain activation at baseline compared to after treatment with resveratrol. The boundary shift integral approach is used on 3D volumetric T1-weighted images to evaluate regions of atrophy, particularly, caudate atrophy.

 

'HDeNERGY'

In order to decipher the metabolic dysfunction contributing to the pathophysiology of Huntington disease, HDeNERGY aims at validating preclinical and clinical methods to assess dynamic parameters of brain energy metabolism using magnetic resonance imaging and spectroscopy. In patients and presymptomatic carriers, the study will combine 31P magnetization transfer to determine the rate of synthesis of phosphocreatine, diffusion weighted spectroscopy to evaluate the diffusion properties of glial and neuronal metabolites and chemical exchange saturation transfer (CEST) to establish brain maps of glutamate levels and pH values.

 

CONTACT: Fanny Mochel MD, PhD, Associate Professor, Neurometabolic Research Group, Pitié-Salpêtrière Hospital, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir.

 
Basal Ganglia and Movement (BGMOV) project

The main goal of the GBMOV study is to better understand the function of the pedonculopontine and the cuneiform nucleus—the two main structures comprising the brainstem mesencephalic locomotor region (MLR)—during gait in healthy volunteers and Parkinson’s disease patients using fMRI.

We constructed a virtual reality task to image brain activity during virtual locomotion, building on our previous work showing that imagining locomotion recapitulates brain activity observed during real gait. We first trained all the subjects to walk down a hallway and second to engage in a virtual environment that mimicked real gait in the same hallway from a first person perspective. In different conditions, the virtual hallway appeared with or without an open doorway. The walking speed in the virtual environment was adapted to each volunteer’s natural walking speed. As a control, we used the same conditions but with movement through the environment mimicking that of a moving treadmill rather than walking.

Using this paradigm, we used whole-brain imaging including the cortex, basal ganglia and brainstem to image the gait networks involved in automatic gait as well as gait with obstacles. These results should provide new understanding on the function of the human MLR and shed light on the precise role of the PPN and CN in the normal and pathological gait.

Contacts: Carine Karachi ( Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. ), Marie-Laure Welter, Eric Bardinet

 
Psychiatry projects

Projects conducted by INSERM U1000

Multimodal imaging of brain development in adolescents and young adults with the assumption that the key periods of brain maturation correspond to transitions and vulnerability to the risk of psychopathology. Particular attention is paid to the study of interactions between environment and genetics during these transition periods and their contributions to individual vulnerability. R20 ans.">esearches are conducted as part of the first cohort of multidisciplinary European adolescents followed from 14 to 20 years and after. French adolescents are imaged CENIR. This cohort is a platform for research on functional brain anatomical deviations that are related to increased risk of psychiatric disorders. The data represent a reference for comparative studies with young Parisian patients suffering from major depressive disorder, anxiety disorders, or addictions.

http://www.inserm-u1000.u-psud.fr


 
Picnic Lab projects

The PICNIC Lab is currently running several imaging projects at the CENIR :

  1. We are studying the activations induced in the occipital cortex of congenitally blind subjects while they are performing a variety of cognitive tasks
  2. We are studying the cerebral reading system, using fMRI activation, combined with resting state connectivity and anatomical connectivity
  3. We are exploring the neural bases of a perceptual illusion of movement
  4. We shall use anatomical, diffusion and functional MRI to identify the lesional and functional connectivity predictors of recovery from attention deficits after right hemisphere damage.
  5. We shall use MEG to identify the neural bases of different aspects of attention within distinct fronto-parietal brain networks, discern their temporal behaviour, and analyse their interaction dynamics in healthy subjects and in right brain-damaged patients.
  6. We are exploring the neural bases of cognitive dissonance both in healthy subjects and in brain-lesioned patients (focal & neurodegenerative disorders) using fMRI, SEEG, scalp EEG and possibly MEG at the CENIR.

Contact: http://icm-institute.org/fr/team/equipe-cohen-naccache-bartolomeo/

 
Motor Neuron Diseases projects

Several academic research projects are conducted at CENIR on Amyotrophic Lateral Sclerosis (ALS) and other motor neuron diseases

-       SPINE: The main goal is to use a multimodal approach for the development of new biomarkers in several motor neuron diseases. There is an unmet need for diagnosis, monitoring and evaluation of new therapies in these rare diseases. The strategy is to extract both structural and functional biomarkers by combining advanced methods of neuroimaging, including brain and spinal cord MRI, and electrophysiology. The studied population includes patients with ALS, spinal muscular atrophy (SMA) and X-linked spinal and bulbar muscular atrophy (SBMA). Electrophysiological and neuroimaging investigations will be carried out longitudinally and data will be correlated with clinical measures.

-       PULSE is a large prospective observational multisite French study of a cohort of 1,000 ALS patients. The main aim is to determine the clinical, biological, imaging, and electrophysiological biomarkers of prognosis. The neuroimaging evaluation for the Paris ALS center will include advanced methods developed by the Laboratory of Biomedical Imaging (LIB), especially for spinal cord imaging.

-       GAITALS (completed). This research program focused on gait initiation and postural control in ALS patients, by using a multidisciplinary approach combining biomechanical and neuroimaging analyses (structural and functional MRI). Understanding of the neural substrates should help to develop adequate therapeutical strategies aimed at improving movement preparation and gait execution in ALS patients

 

Contact: Pierre-François Pradat, MD, PhD. Department of Neurology and Laboratory of Biomedical Imaging, Pitie-Salpetriere Hospital, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir.

 
The Phenotype Project

The project Phenotype has for objective to explore the fundamental elements that constitute our consciousness. The main hypothesis is that structural connectivity in the brain is the elemental base of high cognitive function built from the interaction between primary cognitive processes, with at the top of this hierarchy, the singularity of consciousness. The project is funded for 4 years. The first part of the project is about identifying the different conscious perception’s phenotypes (i.e. Phenotype I) and the second part is dedicated to the investigation of the interaction between conscious perception’s phenotypes and the recovery from conscious perception disorders after a stroke in the right hemisphere (i.e. Phenotype II).

Contact: Michel Thiebaut de Schotten, PhD, Associate Professor, FrontLab, Brain and Spine Institute www.brainconnectivitybehaviour.eu

 
Parkinson's disease projects

CENIR has several research projects on Parkinson's disease (PD) (ICM teams: M Vidailhet/S Lehericy, JC Corvol, A Brice)

- GENEPARK (completed): The main goal of the GENEPARK study was to determine gene expression profiles specific for genetic and idiopathic PD patients using innovative haemogenomic approaches. The second objective of the proposal was to determine correlations between gene expression signatures and different stages of PD and thus provide the basis for early diagnosis and monitoring of disease progression. These changes in blood gene expression were correlated with changes detected by neuroimaging in the brain of PD patients. Such combinations of molecular and morphological markers of disease may ultimately facilitate the selection and monitoring of neuroprotective therapies for PD.

- NUCLEIPARK: The goal of the project is to find new neuroimaging markers of deep brain nuclei in neurodegenerative diseases that can be used for the diagnosis of Parkinsonian syndromes at the early stage and in patients with rapid eye movement sleep behavior disorders (RBD). Lesions of deep brain structures (including the substantia nigra, locus coeruleus, peduncolopontine nculeus, nucleus basalis, medulla oblongata...) will be characterized and biomarker changes will be related to clinical signs, such as cognition, gait and eye movement disorders, RBD and autonomic dysfunction.

- ICEBERG: The primary objectives of this longitudinal 5-year study are to identify the mode of conversion to PD of subjects "at risk" and to validate markers that predict and monitor the progression of dopaminergic lesions and non-dopaminergic in subjects with symptomatic PD. Specific objectives are to identify markers associated with conversion in subjects at risk of developing PD, to characterize the dynamics of PD in the premotor phase, and to characterize and validate early clinical, imaging and biological markers of the disease. Secondary objectives are to characterize different clinical phenotypes of PD with comparable changes.

Contact: http://icm-institute.org/fr/team/equipe-vidailhet-lehericy/

- SN-TRACK: The general goal of this project is to evaluate neurodegeneration in the nigro-striatal pathway in a rat model of PD using novel MRI biomarkers and histological validation. To achieve this goal, the objectives are 1) to evaluate and follow anatomical neuronal damage with diffusion MRI; 2) to evaluate and follow functional connectivity changes with resting-state functional MRI; and 3) to determine and validate the histological correlates of abnormal anatomical and functional connectivity. We use a 6-hydroxy-dopamine rat model, which develops rapid cell death. Our MRI protocols include Q-ball diffusion imaging, an advanced diffusion imaging technique that uses a large number of encoded diffusion directions to better resolve fiber crossing in a single voxel, and resting-state fMRI.

Grant: France Parkinson, 2013 (Contact: Alexandra Petiet, PhD, Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. )

 
Huntington's disease

The TRACK-HD and TRACK-ON projects are major international studies on Huntington’s disease. They aimed to be the most comprehensive study of premanifest and early HD, and helped define the best combination of assessments to be used in clinical trials of disease-modifying treatments in HD. TRACK-HD began in January 2008 and involved 360 subjects at 4 sites internationally:

- London, UK

- Paris, France

- Leiden, Netherlands

- Vancouver, Canada

TRACK-HD used the most cutting-edge assessment techniques available, to assess subjects once a year for a total of 4 years - 5 assessments in total. Each assessment is thorough and lasts one full day. Each visit involves the following assessments:

- A medical interview and neurological examination with a neurologist

- A blood sample, which will be used to find biomarkers for Huntington’s disease, and to provide DNA for studies of the genes that alter the way HD behaves

- A range of cognitive (thinking) tasks carried out on paper and on computer, with a psychologist

- Measurement of your eye movements, using a special set of computerised goggles

- An MRI brain scan lasting about 20 minutes, using the very latest “3 Tesla” scanners

Learn more about Track-HD

 
Ultrabrain - Focused Ultrasound project

The aim of this translational project involving teams of physicists (Langevin Institute, ESPCI), neuroscience research teams and clinicians (ICM, CHU Pitié Salpêtrière) is to develop a unique platform for:

• noninvasive therapy of  brain pathologies using high intensity focused transcranial ultrasound (HIFU)
• high precision non invasive neurostimulation using focused ultrasound
• developement of new innovative approaches of functional imaging using ultrasound.

Around this platform, physicists at the Langevin Institute, recognized as world leaders in the physics of ultrasound waves for medicine and researchers and clinicians of the ICM, will work together to provide a significant advance in the treatment and diagnosis of nervous system diseases, in particular: epilepsy, essential tremor, and brain tumors.

This research program is built on the innovative use of ultrasonic waves, from the modulation of brain activity to the destruction of nerve tissue, to treat some nervous system dysfunction without opening the skull.

Contacts: Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. , Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. , Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir. , Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir.

 


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