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Long-COVID: Study Design and Delineation of Fiber Tracts of the Brainstem

Key Investigators

• Zora Kikinis (Harvard Medical School, USA)
• Nikos Makris (Harvard Medical School, USA)
• Greg Gasic
• Fan Zhang (Harvard Medical School, USA)

Project Description

Symptoms of long-COVID19 might linger for several weeks or months after the initial infection by the SARS-CoV-2 virus. Symptoms are headache, problems with memory and concentration, anxiety, extreme fatigue, chest pain or tightness, gastrointestinal symptoms and difficulty sleeping. In addition, abnormal immune response to viral infection is reported in patients with long-COVID. A dysfunctional brainstem might explain the neuropsychiatric, and autonomic symptoms as a consequence of abnormal immune response.

Objective

1. Are long-COVID symptoms associated with changes in white matter fiber tracts of the brainstem? .
2. Objective B. …
3. Objective C. …

Approach and Plan

1. Segment ROIs in the brainstem.
2. Delineate white matter tracts of the brainstem in a postmortem dMRI data set (50 micro m resolution) and in a 3T dataset of a patient with long-COVID. Candidate tracts are Medial Forebrain Bundle (MFB) and Dorsal Longitudinal Fiber (DLF) and other fiber tracts of the brainstem.
3. Brainstorm hypotheses about which symptoms of long-COVID might be associated with individual tracts of the brainstem.

Progress and Next Steps

1. Segmentation of the Nucleus Tractus Solitarius (solitary complex)–Area Postrema (NTS-AP). NTS-AP plays an impotant role in neuro-immune regulatory loops and autonomic reflexes.

2. Delineated the Medial Forebrain Bundle (MFB) and Dorsal Longitudinal Fiber (DLF) within the brainstem in the postmortem dMRI data set.
3. Run whole brain tractography on the 3T data set.
4. Registering the 3T data set to the postmortem dMRI data set.

Illustrations

Background and References

3D Exploration of the Brainstem in 50-Micron Resolution MRI Richard Jarrett Rushmore, Peter Wilson-Braun, George Papadimitriou, Isaac Ng, Yogesh Rathi, Fan Zhang , Lauren Jean O’Donnell, Marek Kubicki, Sylvain Bouix, Edward Yeterian , Jean-Jacques Lemaire, Evan Calabrese, G Allan Johnson, Ron Kikini, Nikos Makris
Frontiers in Neuroanatomy, 2020

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538715/

Larger gray matter volumes in neuropsychiatric long-COVID syndrome Bianca Besteher, Marlene Machnik, Marie Troll, Antonia Toepffer, Ani Zerekidze, Tonia Rocktäschel, Carina Heller, Zora Kikinis, Stefan Brodoehl, Kathrin Finke, Philipp A. Reuken, Nils Opel, Andreas Stallmach, Christian Gaser and Martin Walter Psychiatry Res. 2022

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444315/pdf/main.pdf