Are T1-weighted and T2-weighted volumetric pipelines interchangeable methodologies for investigating amyotrophic lateral sclerosis pathology in vivo?

PURPOSE: To test the hypothesis that T1-w and T2-w volumetric pipelines are not interchangeable, particularly regarding their differential sensitivity to physiological traits and disease effects in the red nucleus (RN) and substantia nigra (SN).

METHODS

Thirty-one patients with ALS (mean age: 59.39 ± 8.73 years; 23 males) and 21 non-neurodegenerative controls (mean age: 53.43 ± 10.01 years; 16 males). Bilateral RN and SN volumes were automatically extracted using deep learning pipelines optimized for T1-w (OpenMAP-T1) and T2-w (pBrain) images. Volumes were normalized to total intracranial volume. A 2 × 2 × 2 repeated-measures general linear model (GLM) assessed interactions between Method, Region, Side, and Group, controlling for age, sex, BMI, and handedness.

RESULTS

There was no significant main effect of the disease group (p = 0.829) or Method × Group interaction (p = 0.682), indicating both pipelines agreed on the absence of disease-specific macrostructural atrophy. However, a significant four-way Method × Region × Side × Age interaction (P = 0.031) was observed. In the RN, the T2-w pipeline detected robust age-related atrophy (Left: Slope = -1.84 × 10-6; Right: Slope = -1.70 ×10⁻⁶), whereas the T1-w pipeline did not (p > 0.05). Conversely, in the SN, T1-w consistently identified bilateral age-related loss, whereas T2-w yielded lateralized results (Right: p = 0.011; Left: P = 0.465).

CONCLUSIONS

T1-w and T2-w pipelines are not interchangeable. Though both confirm the absence of gross atrophy in this ALS cohort, their differing sensitivity to physiological aging highlights their distinct biological tissue properties, requiring method-specific interpretation.