Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI, 2023, Ajčević et al.

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Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI
Ajčević, Miloš; Iscra, Katerina; Furlanis, Giovanni; Michelutti, Marco; Miladinović, Aleksandar; Buoite Stella, Alex; Ukmar, Maja; Cova, Maria Assunta; Accardo, Agostino; Manganotti, Paolo

Cognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects.

We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis. Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M).

The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE). The hypoperfusion areas identified in the right hemisphere regions were more extensive.

These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.

Link | PDF (Nature Scientific Reports)

 

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Among the 24 included post-COVID-19 patients the reported pre-existing comorbidities and risk factors were hypertension (25.0%), obesity (16.6%), smoke (12.5%), dyslipidemia (12.5%), atrial fibrillation (8.3%), diabetes mellitus (8.3%), ischemic heart disease (4.2%) and autoimmune disease (4.2%). The prevalence of comorbidities and risk factors in the control group were hypertension (22.3%), obesity (13.6%), smoke (18.2%), dyslipidemia (13.6%), diabetes mellitus (4.5%), ischemic heart disease (4.5%) and autoimmune disease (9.0%).

Beside cognitive complaint, the post-COVID-19 manifestations reported during examination were asthenia (62.5%), persistent dyspnea (41.7%), hyposmia (33.3%), headache (25.0%), myalgia/arthralgia (20.8%), dizziness/gait instability (16.7%), palpitations/tachycardia (16.7%), hypo/dysgeusia (12.5%), diarrhea/gastrointestinal distress (4.2%).

The novelty of this study is that we identified a hypoperfusion areas (frontal, temporal, and parietal lobes), similar to the previously reported FDG-PET hypometabolism pattern, in twenty-four post-COVID-19 subjects with persistent cognitive impairment by non-invasive ASL-MRI technique and analysis, without any radiological contrast agents and radiopharmaceuticals.

Our findings showed that ASL imaging and analysis were able to reveal cerebral hypoperfusion pattern in post-COVID-19 subjects with cognitive deficit. As a non-invasive technique, MRI-ASL could be a useful tool for the follow-up of such patients.

 

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Figure 1. Result of group analysis of MRI-ASL data. The group averaged cerebral blood flow (CBF) maps (ml/100 g/min) calculated for the post-COVID-19 group (left column) and healthy subjects (middle column). Right column depicts regions that show significant hypoperfusion in post-COVID-19 patients compared to healthy controls (non-parametric permutation test, p < 0.05, FWE-corrected with TFCE). No regions with a significantly higher perfusion in post-COVID-19 patients compared to healthy controls were detected. Images are reported in the 2-mm MNI152 standard space and in radiological convention.

(MNI152 space means that the anatomy was co-registered between subjects, ie the brains correctly superimposed on each other. Radiological convention is left of image = right of patient, top of image = front of patient, ie imagine patient is lying on back and you're looking up through their feet.)

 

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Table 4. Median (IQR) of regional mean CBF values (ml/100 g/min) of post-COVID-19 subjects and healthy controls at the various ROIs and comparison between two groups. *Statistically significant differences.