The Sense of Smell (SoS) Atlas: Its Creation and First Application to Investigate COVID-19 Related Anosmia With a Comprehensive Quantitative MRI Protocol.

BACKGROUND: The loss of smell (anosmia) has been noted in numerous diseases, including COVID-19. Inflammatory and microstructural alterations are possible underlying mechanisms of anosmia in COVID-19. However, no atlas exists to study olfaction and the associated tissue property changes. PURPOSE: To develop the sense of smell (SoS) atlas, including gray matter regions and white matter tracts of the olfactory circuit, to investigate the underpinnings of COVID-19 related anosmia. STUDY TYPE: Retrospective. SUBJECTS: For the SoS atlas, high-resolution tractograms of 10 healthy controls (HC) of the Human Connectome Project (7 females, 22-35 years) were used. The SoS atlas was applied to 8 subjects with persistent anosmia following COVID-19 (COVID-P, 7 females, 52 ± 12 years), 19 subjects that recovered from COVID-19 anosmia (COVID-R, 14 females, 38 ± 13 years), and 17 HC (8 females, 39 ± 12 years). FIELD STRENGTH/SEQUENCE: 3 T, 3D inversion recovery, 3D fast field echo, and spin-echo echo-planar imaging sequences. ASSESSMENT: To create the SoS atlas, regions were identified and tracts were extracted via tractography following biological constraints. MRI metrics sensitive to alterations in neuroinflammation, axonal degeneration, myelin and macromolecular density, and iron were analyzed. STATISTICAL TESTS: Region-based analysis (p-value < 0.05, false discovery rate (FDR) corrected) and voxel-based analysis p-value < 0.001 uncorrected, FDR-corrected cluster extent = 5 voxels were performed on 15 multisequence-MRI metrics between the three groups. RESULTS: The SoS atlas consisted of 35 regions and, after anatomical curation, the initial 506 tracts were refined to 78. Compared to HC, COVID-P presented alterations in neuroinflammation-related (mean: 41% of total alterations) and axonal degeneration-related (31%) MRI metrics, while COVID-R presented alterations of myelin-related metrics (68%). COVID-P alterations mainly affected the hindbrain (56%), while COVID-R the hindbrain (39%). DATA CONCLUSION: A novel tool, the SoS atlas, was developed to study the olfactory system and applied in combination with multisequence-MRI metrics to investigate the mechanisms of COVID-19 related anosmia. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 1.