Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [ 11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC

1D and 2D correlation spectroscopy of muscle at 7T

A means of providing a detailed analysis of the chemicals involved in muscle metabolism and subsequent alterations with disease or drugs would be an important advance. Two examples of this include the effect of the cholesterol-lowering drugs, known as statins, that commonly cause muscle pain or weakness and can progress to rhabdomyolysis and mortality. The second is the relationship between skeletal muscle triglycerides and insulin resistance, obesity and exercise. Magnetic resonance spectroscopy (MRS) can provide such information by reporting on the intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) in muscle. These two types of lipids reside in different compartments in muscle tissue and thus their protons are shielded differently. Non-invasive quantification of IMCL and EMCL by 1D and 2D 1 H MRS has been reported at 3T . However at 3T there is significant overlap or the resonances in the 1D and crosspeaks in the 2D MR spectra making assignment and definitive correlations with disease difficult. The goal here is to develop 1D and 2D MRS methods at the higher field strength of 7T in order to provide more detailed chemical information than is available at 3

Bone marrow 1D and 2D correlation MR spectroscopy at 7T

The altered chemistry of bone marrow has been shown to be indicative of disease. One-dimensional (1D) proton magnetic resonance spectroscopy (MRS) at 1.5T has previously been used to non-invasively investigate a range of diseases including musculoskeletal tumors , anorexia nervosa , multiple myeloma and osteoporosis . The ratio of saturated to unsaturated lipids was indicative of diagnostic markers for osteoporosis. Two-dimensional (2D) MRS has been shown to be particularly amenable to monitoring lipid alterations with disease. In an attempt to unambiguously assign and monitor resonances, localized 2D correlation spectroscopy (L-COSY) of bone marrow at 1.5T was used to study acute leukemia patients. The results were ambiguous due to crosspeak overlap. The goal of the present study is to develop the L-COSY method to study bone marrow at the higher field strength of 7T and separate those lipid resonances that were composites at 1.5T