Both ATH434 phase 2 studies use QSM signals of the MRI images. QSM signal is used when measuring iron content and shrinking of the brain. This study below explains what the QSM reading is telling us. It looks like QSM reading measures not only iron storage but also the active transport of iron and myelination.

Hum Brain Mapp

. 2024 Jun 15;45(9):e26688.

doi: 10.1002/hbm.26688.

Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination

Zoe Cohen ¹, Laurance Lau ¹, Maruf Ahmed ¹, Clifford R Jack ², Chunlei Liu ^{1 3}

Affiliations expand

• PMID: 38896001

PMCID: PMC11187871 DOI: 10.1002/hbm.26688

Abstract

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.


https://onlinelibrary.wiley.com/doi/10.1002/hbm.26688

QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.