Spotlight: The CMRR Ataxia Imaging Team

Location: University of Minnesota, MN, USA

Year Research Group Founded:  2008

What models and techniques do you use?

A photo of the CMRR Ataxia Imaging Team
A photo of the CMRR Ataxia Imaging Team in 2019. Front row, left to right – Diane Hutter, Christophe Lenglet (PI), Gulin Oz (PI), Katie Gundry, Jayashree Chandrasekaran Back row, left to right: Brian Hanna, James Joers, Pramod Pisharady, Kathryn France, Pierre-Gilles Henry (PI), Dinesh Deelchand, Young Woo Park, Isaac Adanyeguh (insert)

Research Group Focus

What shared research questions is your group investigating?

We use high field, multi-nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) to explore how diseases impact the central nervous system. These changes can be structural, functional, biochemical and metabolic alterations. For example, we apply advanced MRI and MRS methods in neurodegenerative diseases and diabetes.

We also lead efforts in research taking place at multiple different cities across the United States and the world. As you can imagine, studies spread out across such a big area require a lot of coordination and standardization. We design robust MRI and MRS methods to be used in clinical settings like these.

Another important question for our team is how early microstructural, chemical and functional changes can be detected in the brain and spinal cord by these advanced MR methods. We are interested in looking at these changes across all stages of disease.

Why does your group do this research?

The methods we use (MRI and MRS) can provide very helpful information to be used in clinical trials. These biomarkers we look at can provide quantitative information about how a disease is progressing or changing.

There is good evidence that subtle changes in the brain can be detected by these advanced MR technologies even before patients start having symptoms. If we better understand the earliest changes that are happening in the brain, this can in turn enable interventions at a very early stage. For example, we could treat people even before brain degeneration starts to take place.

Why did you form a research group connecting multiple labs?

We came together to form the CMRR Ataxia Imaging Team to benefit from our shared and complementary expertise, experience, and personnel. We can do more together than we could apart.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for multiple different studies. You can learn more about the research we are recruiting for at the following links: READISCA,  TRACK-FA, NAF Studies, and FARA Studies. More information is also available through the UMN Ataxia Center.

A photo of the CMRR Ataxia Imaging Team in 2016
A photo of the CMRR Ataxia Imaging Team in 2016, in front of the historic 4T scanner where the first functional MR images were obtained, in CMRR courtyard. Left to right – Christophe Lenglet (PI), Sarah Larson, Gulin Oz (PI), Dinesh Deelchand, Pierre-Gilles Henry (PI), James Joers, Diane Hutter

What Labs Make Up the CMRR Ataxia Imaging Team?

The Oz Lab

Principal Investigator:  Dr. Gulin Oz

Year Founded:  2006

Our focus is on MR spectroscopy, specifically neurochemistry and metabolism studies. We focus on spinocerebellar ataxias. Also, we have been leading MRS technology harmonization across different sites and vendors.

The Henry Lab

Principal Investigator: Dr. Pierre-Gilles Henry

Year Founded:  2006

We develop advanced methods for MR spectroscopy and motion correction. Then apply these new methods to the study of biochemistry and metabolism in the brain and spinal cord in various diseases. We have been working on ataxias since 2014.

Fun Fact about the Henry Lab: The French language can often be heard in discussions in our lab!

The Lenglet Lab

Principal Investigator:  Dr. Christophe Lenglet

Year Founded:  2011

We develop mathematical and computational strategies for human brain and spinal cord connectivity mapping. We do this using high field MRI. Our research aims at better understanding the central nervous system anatomical and functional connectivity. We are especially interested in looking at this in the context of neurological and neurodegenerative diseases.

Fun Fact

Members of our team have their roots in 7 countries (US, Turkey, France, India, Mauritius, South Korea, Ghana) and 4 continents (North America, Europe, Asia, Africa)

For More Information, check out the Center for Magnetic Resonance Research (CMRR) Website!

Written by Dr. Gulin Oz, Dr. Pierre-Gilles Henry, and Dr. Christophe Lenglet, Edited by Celeste Suart

A promising biomarker to track disease progression in SCA3

Written by Dr. Ambika Tewari Edited by Dr. Gulin Oz

Neurofilament light chain could provide a reliable readout of how far an SCA3 patient’s disease has progressed

How often have you heard that the most effective way to treat a disorder is early intervention? In reality, “early” is not possible for many disorders because patients receive a diagnosis only after the appearance of symptoms. But what if there was a way we could tell that a patient will develop a disease – even before they have any symptoms? Thankfully, that’s exactly what researchers in the field of biomarkers are trying to do. Biomarkers are biological indicators that are not only present in patients before the manifestation of symptoms, but can also be used to measure disease progression. In the SCA field, there have been a recent series of articles that have shed light on a promising biomarker for SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease, is the most common dominantly-inherited ataxia. It is caused by an expansion of CAG repeats (a small segment of DNA that codes for the amino acid glutamine) in the ATXN3 gene. An important feature of SCA3, as well as in other spinocerebellar ataxias, is the progressive development of symptoms. Symptoms usually occur across decades, and can be divided into three major phases: asymptomatic, preclinical, and symptomatic. In the asymptomatic phase, there is no evidence of clinical symptoms (even though the patient has had the SCA-causing mutation since birth). In the preclinical stage, patients show unspecified neurological symptoms such as muscle cramps and/or mild movement abnormalities. By the symptomatic (i.e., clinical) stage, patients have significant difficulty walking.

A Spinal Cord Motor Neuron sample stained purple.
Neurofilament light chain (NfL) is an important building block of neurons. But when neurons are damaged, NfL is released. Image of a spinal cord motor neuron courtesy of Berkshire Community College.

Currently in SCA research, disease progression is measured using the Scale for the Assessment and Rating of Ataxia (SARA). A score of 3 or more on the SARA differentiates clinical and preclinical groups. Structural and functional brain imaging methods (such as MRI) also track the progressive nature of the disease, like the SARA, but give us a visual picture of changes in the brain. Together, these methods have provided the SCA community with important insights into the clinical spectrum of each specific disease and its rate of progression. And, with the exciting progress we have recently made in the realm of SCA3 therapeutics, a biomarker that is cost-effective and easy to measure (like in a blood test) could provide a convenient way to assess how effective a potential treatment is.

Continue reading “A promising biomarker to track disease progression in SCA3”

Aperçu Rapide: Qu’est-ce que l’imagerie par résonance magnétique (IRM) ? A quoi sert elle dans l’Ataxie ?

Qu’est-ce que c’est?

L’imagerie par résonance magnétique (IRM) est un type de technologie utilisé pour prendre des photos détaillées du corps. Il est couramment utilisé pour détecter des anomalies dans le corps, diagnostiquer des maladies et surveiller régulièrement les patients en cours de traitement. Il peut générer des images tridimensionnelles de tissus non osseux, tels que le cerveau. Les procédures d’IRM sont non invasives, nécessitent une préparation minimale et ne sont pas associées à des risques pour la santé, car elles n’utilisent pas de types de rayonnement nocifs tels que les rayons X.

Comment ça marche?

Les tissus humains contiennent de l’eau, qui contient de très petites particules appelées protons qui se comportent comme de minuscules aimants. Un appareil d’IRM utilise de gros aimants puissants pour générer un champ magnétique qui peut modifier la rotation de ces particules dans votre corps, ce qui les aligne sur le champ magnétique. Des ondes radio non nuisibles sont ensuite émises par le patient, modifiant ainsi la direction de ces particules, de sorte qu’elles ne sont plus alignées sur le champ magnétique. Les ondes radio sont alors désactivées et les particules peuvent alors se réaligner avec le champ magnétique. Différents types de tissus et de structures dans le corps auront des particules qui se ré-alignent différemment, ce qui peut être détecté par la machine pour générer une image détaillée en noir et blanc de la zone balayée du corps. En plus de ces informations structurelles, les analyses IRM peuvent fournir des informations sur la manière dont le cerveau est câblé, les niveaux de produits chimiques importants, le flux sanguin, le métabolisme et les fonctions cérébrales en acquérant des informations différemment avec le même appareil.

Vue 3D d'un cerveau humain entier prise par IRM, sous deux angles.
Vue 3D d’un cerveau humain entier prise par 7 Tesla IRM. Photo offerte gracieusement par B.L. Edlow et al, bioRxiv, 2019

Comment se préparer pour une IRM ?

Étant donné que l’IRM utilise un gros aimant, les appareils électroniques et les objets métalliques, tels que les lunettes et les bijoux, doivent être retirés. Aucune autre préparation n’est généralement requise pour l’analyse. Les patients doivent rester immobiles pour générer une image claire. Les patients n’ont pas besoin d’être sous sédation, sauf s’ils ont du mal à rester allongés pendant l’intervention. Les examens d’IRM obtenus à des fins de recherche n’utilisent pas l’anesthésie pour éviter des risques inutiles aux participants à la recherche.

Que se passe-t-il lors d’une IRM?

Le patient s’allonge sur une table qui se déplacera dans la chambre en forme de tunnel. Le patient est généralement réveillé et restera dans la chambre après plusieurs analyses (environ 30 à 60 minutes). Au fur et à mesure de la numérisation, il y a souvent des bruits mécaniques forts. Des bouchons d’oreilles sont donc fournis pour la protection. Certains patients peuvent souffrir de claustrophobie ou être dérangés par les bruits. En vous familiarisant davantage avec la procédure, en écoutant de la musique ou en fermant les yeux, vous pourrez soulager l’inconfort pendant le scan.

Que recherchent les médecins chez les patients atteints d’une Ataxie spinocérébelleuse (SCA) ?

Les examens IRM sont souvent utilisés pour imager le cerveau afin de détecter les signes d’ataxie spinocérébelleuse (SCA), en particulier dans une région du cerveau appelée cervelet. Le SCA est associé à la perte de cellules cérébrales et se traduit par une réduction du volume de tissu cérébral dans l’image IRM.

Si vous souhaitez en savoir plus sur l’imagerie par résonance magnétique (IRM), jetez un œil à ces ressources de l’IRM Québec et de l’Université Laval.

Plus de ressources sur l’IRM en anglais peuvent être trouvées aux National Institutes of Health et à la Mayo Clinic.

Écrit par Dr. Claudia Hung, Édité par Dr. Gülin Öz, Traduction française par: L’Association Alatax, Publication initiale: 15 novembre 2019.

Snapshot: What is Magnetic Resonance Imaging (MRI)?

What is it?

Magnetic resonance imaging (MRI) is a type of technology used to take detailed pictures of the body. It is commonly used to detect abnormalities in the body, diagnose diseases, and to regularly monitor patients who are undergoing treatments. It can generate three-dimensional images of non-bony tissues, such as the brain. MRI procedures are non-invasive, require minimal preparation, and are not associated with health risks, as it does not use harmful types of radiation such as X-rays.

How does it work?

Human tissues contain water, which contain very small particles known as protons that behave like tiny magnets. An MRI machine uses large, powerful magnets to generate a magnetic field that can change how these particles rotate in your body, making them align with the magnetic field. Non-harmful radio waves are then pulsed through the patient, changing the direction of these particles, such that they are no longer aligned with the magnetic field. The radio waves are then turned off, and the particles can then re-align with the magnetic field. Different types of tissue and structures in the body will have particles that re-align differently, which can be detected by the machine to generate a detailed black and white image of the scanned area of the body. In addition to such structural information, MRI scans can provide information about how the brain is wired, levels of important chemicals, blood flow, metabolism, and brain function by acquiring information differently with the same machine.

3D view of an entire human brain taken by MRI, shown from two angles.
3D view of an entire human brain taken by 7 Tesla MRI. Photo courtesy of  B.L. Edlow et al, bioRxiv, 2019.

How do you prepare for an MRI scan?

Since an MRI scan uses a large magnet, electronic devices and metal objects, such as glasses and jewelry, must be removed. There is usually no other preparation required for the scan. Patients must lie very still to generate a clear image. Patients do not need to be sedated, unless they have trouble lying still for the procedure. MRI scans that are obtained for research do not use anaesthesia to avoid unnecessary risk to research participants.

What happens during an MRI scan?

The patient lies down on a table that will move into the tunnel-shaped chamber. The patient is usually awake and will remain in the chamber as several scans are taken during the procedure (about 30-60 minutes). As the scan proceeds, there are often loud mechanical sounds, so earplugs are provided for protection. Some patients may experience claustrophobia, or are bothered by the noises. Becoming more familiar with the procedure, or listening to music or closing your eyes can help alleviate discomfort during the scan.

What do doctors look for in patients with SCAs?

MRI scans are often used to image the brain to detect signs of spinocerebellar ataxia (SCA), especially in a region of the brain known as the cerebellum. SCA is associated with brain cell loss, and appears as reduced volume of brain tissue in the MRI image.

If you would like to learn more about Magnetic Resonance Imaging (MRI), take a look at these resources by the National Institutes of Health and the Mayo Clinic.

Snapshot written by Dr. Claudia Hung and edited by Dr. Gülin Öz.