Mass General's CTRU Advances Research in Complex Brain Disorders

Massachusetts General Hospital recently opened the Clinical and Translational Research Unit (CTRU), a multidisciplinary clinical research facility founded to accelerate research in preventing, managing and curing complex brain disorders like mood and psychotic disorders, neurodegenerative diseases, epilepsy, multiple sclerosis and traumatic brain injury.

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"The CTRU will support investigators in the discovery and implementation of promising therapeutics through novel clinical trials as well as new diagnostic and biomarker tools to better understand complex brain and other health conditions," says Steven Arnold, MD, director of the newly established CTRU, head of Translational Neurology and managing director of the Interdisciplinary Brain Center at Massachusetts General Hospital.

Over 200 users in the Mass General research and clinical communities of neurology, psychiatry and neuroradiology have signed up to utilize the center. The 26-room clinical research facility will also be a site for academic-industry partnerships, multidisciplinary biomedical education, and contractual research.

From Laboratory Research to Neuroscience Clinical Trials

According to Dr. Arnold, researchers in neurology and psychiatry often encounter logistical challenges when scaling from animal or laboratory models to human studies. The location and advanced resources of the CTRU make this transition more seamless for research teams.

The state-of-the-art CTRU facility is strategically located one floor above the Athinoula A. Martinos Center for Biomedical Imaging. Clinical investigators can order brain imaging, such as magnetic resonance imaging (MRI) or positron emission tomography (PET) scans, and send patients right downstairs. "The location is a unique feature of the CTRU because patients just take an elevator down one floor to have their neuroimaging done. Researchers don't have to schedule them to go to another facility," Dr. Arnold says.

Advanced Technology and Data Acquisition Tools

The CTRU is equipped with what Mass General refers to as Big Data & Digital Health Hub resources. These novel capabilities include physiological measurement technologies, fully equipped exam and procedure rooms with audio/visual recording, mobile and wearable digital health technologies, automated ultra-sensitive fluid biomarker assays, and data visualization and virtual reality capabilities. These advanced resources give researchers the ability to creatively design new experimental paradigms, collect data on study participants that elucidate mechanisms of disease and test new biomarkers for diagnosing, staging and tracking disease progression and response to novel therapeutics.

Big Data & Digital Health Hub resources include specialized electroencephalography (EEG) equipment for the MRI environment located in the Martinos Center, providing simultaneous recordings of electrical activity in the brain. This multimodal neuroimaging is particularly powerful for studying epileptic activity.

Near-infrared spectroscopy (NIRS) imaging equipment is also available at the CTRU to noninvasively measure blood changes in the brain associated with brain activity while study participants engage in cognitive and emotional activities. NIRS can help researchers dynamically visualize changes in the brain with disease, injury and novel therapeutic interventions.

Wearable and remote digital devices are available to track participants in their homes for ecological monitoring of physical and cognitive activity, sleep, cardiovascular and other physiological functions.

Advanced Data Visualization Room

The CTRU operates on a high-end computing system that integrates diverse clinical data, including clinical, multi-omic, neuroimaging, physiological and electronic health records. Teams can collaboratively visualize and interact with data in the Advanced Data Visualization Room, which has holographic and virtual reality data visualization in addition to a 9-panel hyperwall.

"We have a hyperwall, holography and VR projection and headsets so teams can better visualize their data. For example, they can look at a brain's functional connectivity and walk through the brain in 3D, rotating it for different views, or reconstruct microscopic histological and subcellular data in four dimensions," explains Dr. Arnold.

Multi-Sensor Clinical Exam Rooms

Ten of the 14 exam rooms in the CTRU have high-resolution audio and video recording equipment to capture high-quality recordings of research participants, allowing investigators to analyze individuals' physical, cognitive and emotional behaviors. The recordings are helpful when studying disorders that impact the nervous system—some small movements, such as tremor and rigidity in Parkinson's disease or emotional facial expressions in depression, can be detected and measured on high-resolution video more easily than with the naked eye.

"Voice, eye tracking, pupillometry, motor control and sensory functions can all be measured with the advanced technology in the CTRU exam rooms," says Dr. Arnold. "At the same time, study participants may be hooked up to an EEG or [electrocardiogram] ECG. It gives investigators a comprehensive profile of the nervous system function in an individual."

Additionally, four radiofrequency-shielded rooms provide an electromagnetically quiet environment for conducting sensitive electrophysiological recordings.

Researchers use the virtual reality room ("VR Cave") to conduct complex behavioral assessments. Virtual reality allows for the study of cognition and behavior in a controlled environment—participants interact with sensory illusions created in VR under the guidance of the research team. Investigators might also use VR in combination with EEG and functional near-infrared spectroscopy (fNIRS) to measure brain activity while participants engage in VR-simulated social tasks.

Biofluids Marker Core

The CTRU's in-house laboratory has the capacity to run biochemical assays on participant blood and spinal fluid samples to measure biomarkers for neuroscience application. Dr. Arnold says research teams can choose from a menu of laboratory assays to monitor study participants.

"For example, for individuals with lasting neurological symptoms from COVID-19, like brain fog, we can measure certain proteins in the blood and spinal fluid and detect injury or inflammation in the nervous system. That can be a very informative tool to develop better diagnostics or treatments for people with long COVID."

Alzheimer's disease and other neurodegenerative diseases, cerebrovascular disease, epilepsies, and neuropsychiatric disorders are common applications for these biomarkers as well.

Facilitating Collaborations Between Biotech, Pharma and Academic Medicine

The CTRU will grow Mass General's extensive collaborations with academic and commercial biotechnology and pharmaceutical interests. The new research facility will be a site for academic-industry partnerships, multidisciplinary biomedical education, workforce development and contractual research

Mass General researchers at the CTRU will also lead efforts in developing gene and cell therapies, translating to treatment for patients through clinical trials to treat rare and complex conditions.

The CTRU's investment in technology and research staff make this partnership possible. Nurse practitioners, medical assistants, nurses and basic and clinical investigators with specialized expertise are available to assist research partners in developing and implementing neuroscience-related studies.

"Commercial biotechnology and pharmaceutical companies can develop research projects with our investigators here at the CTRU. We can also implement the studies because we have all the support services and facilities necessary to conduct the research. It's a true collaborative space," says Dr. Arnold.

"Mass General put a tremendous amount of thought and planning into this building. The goal was to improve human brain health through research, and the CTRU was intentionally designed to facilitate that."

Learn more about Mass General Neuroscience

Learn about the Department of Neurology