Longitudinal Assessment of Intravoxel Incoherent Motion Diffusion-Weighted MRI Metrics in Cognitive Decline

Background: Advanced diffusion-based MRI biomarkers may provide insight into microstructural and perfusion changes associated with neurodegeneration and cognitive decline. Purpose: To assess longitudinal microstructural and perfusion changes using apparent diffusion coefficient (ADC) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in cognitively impaired (CI) and healthy control (HC) groups. Study Type: Prospective/longitudinal. Population: Twelve CI patients (75% female) and 13 HC subjects (69% female). Field Strength/Sequence: 3 T; Spin-Echo-IVIM-DWI. Assessment: Two MRI scans were performed with a 12-month interval. ADC and IVIM-DWI metrics (diffusion coefficient [D] and perfusion fraction [f]) were generated from monoexponential and biexponential fits, respectively. Additionally, voxel-based correlations were evaluated between change in Montreal Cognitive Assessment (ΔMoCA) and baseline imaging parameters. Statistical Tests: Analysis of covariance with sex and age as covariates was performed for main effects of group and time (false discovery rate [FDR] corrected) with post hoc comparisons using Bonferroni correction. Partial-η² and Hedges' g were used for effect-size analysis. Spearman's correlations (FDR corrected) were used for the relationship between ΔMoCA score and imaging. P < 0.05 was considered statistically significant. Results: Significant differences were found for the main effects of group (HC vs. CI) and time. For group effects, higher ADC, IVIM-D, and IVIM-f were observed in the CI group compared to HC (ADC: 1.23 ± 0.08^.10⁻³ vs. 1.09 ± 0.07^.10⁻³ mm²/sec; IVIM-D: 0.82 ± 0.01^.10⁻³ vs. 0.73 ± 0.01^.10⁻³ mm²/sec; and IVIM-f: 0.317 ± 0.008 vs. 0.253 ± 0.009). Significantly higher ADC, IVIM-D, and IVIM-f values were observed in the CI group after 12 months (ADC: 1.45 ± 0.05^.10⁻³ vs. 1.50 ± 0.07^.10⁻³ mm²/sec; IVIM-D: 0.87 ± 0.01^.10⁻³ vs. 0.94 ± 0.02^.10⁻³ mm²/sec; and IVIM-f: 0.303 ± 0.007 vs. 0.332 ± 0.008), but not in the HC group at large effect size. ADC, IVIM-D, and IVIM-f negatively correlated with ΔMoCA score (ρ = −0.49, −0.51, and −0.50, respectively). Data Conclusion: These findings demonstrate that longitudinal differences between CI and HC cohorts can be measured using IVIM-based metrics. Level of Evidence: 2. Technical Efficacy Stage: 2.