Thalamic quantitative susceptibility mapping and susceptibility source separation: a critical narrative review of evidence and interpretation.

Quantitative susceptibility mapping (QSM) measures net tissue magnetic susceptibility, which can conceal coexisting contributions of opposite sign. This is relevant to the thalamus, where nuclei differ in cellular composition, myelinated fibers, and susceptibility contrast. This narrative review evaluates what QSM and magnetic susceptibility source separation, including χ-separation, currently establish about thalamic alterations in aging and neurological disease. The synthesis prioritizes human thalamic evidence and distinguishes it from methodological validation, findings outside the thalamus, and animal experiments. We use paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) as the principal notation, with PCS nonnegative and DCS nonpositive. These model-derived components describe magnetic behavior and do not independently identify iron, myelin, calcium, amyloid, or tau. Reduced thalamic bulk susceptibility is repeatedly reported in multiple sclerosis, whereas findings in Alzheimer's disease and Parkinson's disease are less consistent. Differences in acquisition, referencing, segmentation, cohort composition, and treatment of atrophy affect interpretation, although methodological variability does not explain every disagreement. Source separation can provide information concealed by net susceptibility, but depends on relaxation modeling, acquisition conditions, and reconstruction assumptions. Evidence for thalamic protein mapping, calcification of characterization, and treatment monitoring remains limited or indirect. PCS and DCS are research measurements with potential biological interpretability; standardized acquisition and processing, independent tissue validation, longitudinal replication, and clinically useful decision thresholds are required before they can be regarded as validated clinical biomarkers.