Elevated cerebral oxygen extraction in patients with post-COVID conditions, 2024, Liu et al.

[SNT Gatchaman]

Elevated cerebral oxygen extraction in patients with post-COVID conditions
Peiying Liu; Thomas Ernst; Huajun Liang; Dengrong Jiang; Eric Cunningham; Meghann Ryan; Hanzhang Lu; Shyamasundaran Kottilil; Linda Chang

OBJECTIVES
Dysfunction of cerebral microcirculation due to SARS-CoV-2 infection has been postulated to be a plausible mechanism for the neurological symptoms of post-COVID-19 conditions (neuro-PCC), affecting oxygen homeostasis in the brain. In this study, we aimed to investigate the balance between cerebral oxygen delivery and consumption, measured by oxygen extraction fraction (OEF), in patients with neuro-PCC.

METHODS
25 participants with neuro-PCC (8 previously hospitalized and 17 not hospitalized) and 59 age-matched healthy controls were studied. Global OEF was quantified using TRUST MRI and compared across the three groups. Associations between OEF and neurobehavioral measures were also evaluated in participants with neuro-PCC.

RESULTS
OEF was significantly different (one-way ANCOVA-p=0.046) among the three groups, after accounting for age and sex. On post-hoc analyses, previously hospitalized neuro-PCC participants had significantly higher OEF (42.40 ± 5.40 %) than both uninfected controls (37.70 ± 5.09 %, p=0.032) and neuro-PCC participants without hospitalization (37.02 ± 5.05 %, p=0.015). Within the participants with neuro-PCC, OEF was significantly associated with locomotor function assessed with the 4-m walk gait speed score (β=−0.03, r=0.34, p=0.003).

CONCLUSIONS
Participants with neuro-PCC had altered cerebral OEF, which is also associated with slower locomotion. OEF is a promising marker for studying neuro-PCC.

Link | PDF (NeuroImmune Pharmacology and Therapeutics) [Open Access]

 

[SNT Gatchaman]

The non-hospitalized neuro-PCC participants were not different from the uninfected controls. In addition to the group effect, OEF varied by age (p<0.001, Figure 1b) but not by sex (p=0.177).

The age-dependent increase in OEF in our participants is consistent with prior studies. The increase of OEF with age is thought to reflect age-related compensation in brain function during normal aging. The elevated OEF in our hospitalized neuro-PCC participants remained significant after we co-varied for age. Therefore, this elevated OEF can be attributed to microvascular damage-related alteration in oxygen homeostasis instead of age-related compensation.

In our study, while higher global OEF was found primarily in participants with neuro-PCC who were hospitalized, the OEF in the neuro-PCC participants who were not hospitalized were relatively normal. These findings suggest that the long-lasting alteration in oxygen homeostasis may only be present in more severe cases of SARS-CoV-2 infection. Currently, we are conducting a followup study to investigate whether the elevated OEF would normalize 1-year after the initial MRI in our participants with neuro-PCC who were hospitalized.

This study has several limitations. First, we only evaluated global OEF which lacks spatial resolution. Thus, it is unclear whether the elevated OEF is present throughout the brain or only in a few brain regions. Therefore, future study should include an improved MRI technique that can assess regional OEF.

 

[Eleanor]

OEF is measured with the participants resting, am I right?

 

[SNT Gatchaman]

OEF is measured with the participants resting, am I right?

Yes, they'd be lying supine, quietly in the scanner at most listening to a background audio track. For this type of study I would expect there to be no audio playing as it could be a confounder when attempting to measure brain metabolism. Just background scanner noise can have effects though, see fMRI-acoustic noise alters brain activation during working memory tasks (2005, NeuroImage). So as long as the same protocol was used in all groups that's probably the best we can do.

All participants underwent an MRI session on 3T Siemens Prisma MRI (Siemens Healthcare, Erlangen, Germany). Global venous oxygenation (Yv) was measured noninvasively with the TRUST MRI technique at the superior sagittal sinus to calculate the OEF [10]. The TRUST technique uses the spin-label principle on the venous side to separate pure venous blood and measure its T2, and then convert T2 to Yv using a calibration plot based on the well-known relationship between T2 and Yv [13]. This technique has been validated [13], and shown excellent reproducibility within subjects [14] and across sites [15] and MRI vendors [16].

[10] is Quantitative evaluation of oxygenation in venous vessels using T2-Relaxation-Under-Spin-Tagging MRI (2008, Magnetic Resonance in Medicine)

13 and 14 include this paper's lead author.

[13] is Calibration and validation of TRUST MRI for the estimation of cerebral blood oxygenation (2012, Magnetic Resonance in Medicine)

[14] is Test–retest reproducibility of a rapid method to measure brain oxygen metabolism (2013, Magnetic Resonance in Medicine)

 

[Eleanor]

Thanks! It would be so interesting to know what happens to blood flow and oxygenation during activity - I guess we're quite a way off having the tech to see that.

 

[SNT Gatchaman]

And measuring blood flow at rest and during activity in an upright MRI scanner might really show us something.