Ultrahigh resolution 7-Tesla imaging of structural abnormalities, cerebrospinal fluid flow, and other symptom mechanisms in patients with infection-associated chronic disease

Project summary:

A carefully conceptualized series of MRI brain scans using ultrahigh resolution 7-Tesla imaging in patients with infection-associated chronic disease (eg: LongCovid and ME/CFS). The planned sequences will, in a reliable and replicable fashion, detect a range of potential symptom mechanisms such as structural abnormalities (e.g., craniocervial instability), autonomic dysfunction, cerebrospinal fluid flow problems, brain blood flow issues, intracranial pressure evidence, and dysregulation of vagus nerve signaling.

Project background:

Many patients with infection -associaed chronic conditions including Long COVID and ME/CFS report symptoms include dysautonomia, diffuse pain, sleep problems, flu-like symptoms, trouble concentrating, and nausea. The central role of the brainstem in the sickness behavior response, autonomic control, and arousal suggests that dysfunctional brainstem signaling may be an important driver of PASC symptoms that overlap with those of ME/CFS. Indeed, the dorsal brainstem is packed with nuclei governing symptoms such as dysautonomia, sleep problems, nausea, pain, and sickness (Figure 5). Several studies have reported functional and structural brainstem abnormalities in ME/CFS (Barnden et al., 2019; VanElzakker et al., 2019; Shan et al., 2020), including one study demonstrating brainstem glial activation positively correlated with cognitive impairment (Nakatomi et al., 2014). Due to its location between the 4th ventricle and foramen magnum, the dorsal brainstem is also uniquely vulnerable to alterations in cerebrospinal fluid pressure. An ongoing area of research centers on whether long-term illness initiated by acute infection may be associated with variance in the craniocervical junction (Rowe et al., 2018; Bragée et al., 2020) or sacral spinal cord structure (Mantia et al., 2015). Such an association could reflect a pre-existing vulnerability factor, or a consequence of pathology related to acute illness effects on cerebrospinal fluid pressure, infection, or inflammatory effects on the elasticity of the meninges or laxity of craniocervical structural ligaments.

The brain scans are being performed at the Harvard/MIT-affiliated Martinos Center For Biomedical Imaging – regarded as one of the premiere medical imaging centers in the world, and a hub for the top researchers in related fields. Indeed, project team member Dr. Jonathan Polimeni is Director of the Center’s Ultra-High Field Imaging and their top brainstem imaging expert. The Martinos Center’s 7-Tesla MRI scanner allows for the most detailed neuroimaging in the world. It has more than four times the magnetic field strength of the 1.5 Tesla scanners used in most clinical settings. It can consequently be used to study structural issues and problems with blood and cerebrospinal fluid flow that simply cannot be seen with other MRIs.