Brain

We are investigating novel radiotracers and PET and MR imaging techniques to improve the diagnosis, characterization, and treatment of age-related diseases such as Alzheimer’s (AD) and Parkinson’s (PD), frontotemporal dementia, etc.

Synaptic vesicle glycoprotein 2A (SV2A), a protein found in synaptic vesicles, is being investigated as a PET biomarker for synaptic density. SV2A levels in the brain are correlated with synaptophysin, a marker of synapse density, underscoring the versatility of SV2A-PET imaging in the diagnosis of neurological disorders.

Synaptic loss is a major structural correlate of cognitive impairment in Alzheimer’s disease (AD). Measuring synaptic density in vivo could expedite the development of AD treatments. Synaptic loss in AD differs from amyloid, tau, and FDG patterns seen in other types of PET imaging, although correlations exist.

Investigator: Richard Carson

We are conducting research to develop a better diagnosis for Parkinson’s disease (PD) and to help establish the next generation of brain imaging, which will be vital for monitoring progression and evaluating new treatments. Currently we are using synaptic density and dopamine transporter imaging. We are also interested in the non-motor symptoms of Parkinson’s disease such as depression, anxiety, and sleep disturbance. The ultimate goal of our research is to inform new treatments that alleviate the symptoms and improve quality of life in those living with PD.

References:

• Honhar P, Ebrahimian Sadabad F, et. al., Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights. Brain Commun. 2024 Oct 2;6(5):fcae345. doi: 10.1093/braincomms/fcae345.
• Matuskey D, Tinaz S, Wilcox, KC, et. al., In vivo imaging detects synaptic loss in Parkinson’s disease. Ann Neurol. 2020 Mar;87(3):329-338. doi: 10.1002/ana.25682.

Read more on our NeuroPET research program page.

Investigator: David Matuskey

The Fredericks lab is based upon the premise that neurodegenerative diseases are fundamentally disorders of specific brain circuits. We are interested in the earliest “preclinical” stages of diseases like Alzheimer’s disease and Parkinson’s disease, and in clinical heterogeneity within these diseases once they are symptomatic. In studying neurodegenerative disease from these more novel angles, we can ask and answer questions about the earliest changes that characterize the illness, and deduce generalizable principles about how the illness operates across circuits in its full spectrum of phenotypes. We use multimodal neuroimaging, including structural and functional MRI and tau PET, and analytic techniques including graph theoretic approaches and connectome-based predictive modeling, to answer our questions.

For more details please visit the Fredericks lab website.

Investigator: Carolyn Fredericks

This project uses synaptic density imaging to study behavioral variant frontotemporal dementia (bvFTD) using [18F]SynVestT-1. This radiotracer binds to a protein in synapses and is the first to provide synaptic measurements in living people, which is centrally important in bvFTD based upon strong supporting evidence from animal models, genetic research and post-mortem studies. By studying this tracer and comparing it to a clinically available biomarker, 18F-FDG, this study could be the first step to a better measure of early detection and progression in bvFTD.

Read more on the NeuroPET research program page.

Investigator: David Matuskey with Arman Fesharaki

MS is a chronic inflammatory disease that affects the brain by causing demyelination and is the second most common cause of disability in young adults. Brain MRI is currently the preferred diagnostic imaging method for MS, but it lacks sensitivity and specificity for monitoring disease pathology. Molecular imaging with PET using translocator protein (TSPO) radioligands allows for the in vivo visualization of microglial activation. TSPO PET imaging can quantify microglial activity at any given time and has the potential to monitor disease progression and evaluate treatment responses in MS patients.

Investigator: Kelly Cosgrove

See our instrumentation page and the DMI lab page for more information on DMI technology.

After an oral dose of 2H-labeled glucose, DMI provided unprecedented contrast based on glucose metabolism in a patient with a GBM brain tumor. We were able to visualize the Warburg effect, a metabolic process in which cancer cells use glycolysis to produce energy, even when oxygen is present, in a patient with GBM after oral 2H-glucose intake.

Investigator: Robin de Graaf, Henk de Feyter

Despite being one of the most common and widespread neurological diseases, the etiology of essential tremor (ET) is only partially understood. Clinical evidence, however, points to the cerebellum as an origin of the disease. Synaptic density imaging is being used as an in vivo biomarker to quantify synaptic density loss in ET and has the potential to be a reliable and diagnostically useful marker of ET progression.

Read more on the NeuroPET research program page.

Investigator: David Matuskey with Elan Louis (UTSW)

Because ASD is poorly understood at the molecular level, we are investigating metabotropic glutamate receptor 5 (mGluR5) density, a potential mechanism for autistic dysfunction, supported by animal models, genetic research, post-mortem studies, and related single-gene disorders. By linking this information to a detailed assessment of social-communicative dysfunction, it provides the first data supporting mechanistic dysfunction from the molecular level to neural systems to clinical behavior. This is crucial as there are no clinical ASD biomarkers and medications to regulate glutamate receptors exist. Understanding mGluR5 differences in ASD has direct implications for treatment. We are also using a synaptic density PET tracer, binding to synaptic vesicle glycoprotein 2A (SV2A), to investigate the molecular underpinnings of the autism phenotype. We have found that more autistic features are associated with lower synaptic density.

Investigator: David Matuskey with James McPartland

Brain networks, complex interconnected systems of neurons, play crucial roles in cognitive, emotional, and behavioral functions. Imaging techniques like Functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI) have revolutionized our understanding of these networks. fMRI measures brain activity and identifies functional connectivity, while DTI maps white matter tracts connecting brain regions. Imaging brain networks helps understand how diseases disrupt normal connectivity, aids diagnosis, and develops targeted treatments. It also tracks changes in networks over time, illustrating the brain’s adaptability to injury, learning, and therapy.

Our research focuses on the intersection of brain connectomics, neuroscience, and multiomics, with a particular emphasis on neurodegenerative diseases such as Alzheimer’s disease and other types of dementia. Over the years, we have developed innovative imaging biomarkers based on PET and network/graph theory metrics. Currently, we are also focusing our investigations on integrating neuroimaging-connectomics with cerebral gene expression to identify novel molecular targets for PET tracers and therapeutic purposes.

Investigator: Jorge Sepulcre

The MINDS lab conducts state-of-the-art research to help us better measure and understand human functional connectivity. Understanding the complex network of interconnected regions in the brain, their interactions, and their role in behavior is a central question in human neuroscience. The MINDS lab is addressing these questions through fMRI technology. The lab develops novel statistical and machine learning methods for functional connectivity to address challenges of large-scale neuroscience data. Key research areas include connectome-based predictive modeling, high-dimensional imputation, multi-modality manifold learning, and advanced statistical inference to enhance power and reliability.

Investigator: Dustin Scheinost

Our studies focus on the development of the brain’s functional organization in fetuses, neonates, and infants. The MINDS lab research in this area involves developing state-of-the-art tools and analytic pipelines to meet the challenges of imaging early brain development with advances in image acquisition, image analysis, and statistical analysis.

Investigator: Dustin Scheinost