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Purpose <p>This study evaluated the peak width of skeletonized mean diffusivity (PSMD) as a quantitative imaging marker in patients with magnetic resonance imaging-negative (MRI-negative) temporal lobe epilepsy (TLE), accounting for age and sex effects.</p> Methods <p>This retrospective study included 34 MRI-negative TLE patients and 40 age- and sex-matched healthy controls (HCs). PSMD was calculated using tract-based spatial statistics and histogram analysis. Hierarchical regression identified PSMD determinants. Receiver operating characteristic analysis compared uncorrected and age- and sex-corrected PSMD, with the latter validated by 10-fold cross-validation.</p> Results <p>PSMD was significantly elevated in patients versus HCs (2.545 × 10<sup>−</sup>⁴ mm²/s vs. 2.340 × 10<sup>−</sup>⁴ mm²/s, <i>p</i> = 0.004) and independently associated with TLE (OR = 2.39, <i>p</i> = 0.011). Sensitivity analysis confirmed robustness (OR = 2.22, <i>p</i> = 0.013). In addition, males showed higher PSMD than females in both patients (<i>p</i> = 0.022) and HCs (<i>p</i> &lt; 0.001). Furthermore, age (β = 0.453, <i>p</i> = 0.005) and male sex (β = 0.539, <i>p</i> = 0.014) were associated with higher PSMD. Age/sex correction improved specificity (82.5% vs. 67.5%) but reduced sensitivity (64.7% vs. 52.9%), with an area under the curve (AUC) of 0.696. AUC improvement was non-significant (<i>p</i> = 0.676); cross-validated AUC was 0.628.</p> Conclusion <p>PSMD is a quantitative marker of diffuse white matter pathology in MRI-negative TLE, modulated by demographic factors. Consistent sex effects across groups indicate biological rather than disease-specific variation. Demographic adjustment improves specificity but not overall accuracy, supporting PSMD for group-level cross-sectional studies. Sex effects must be controlled for in white-matter diffusion MRI.</p>

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Peak width of skeletonized mean diffusivity as a quantitative imaging marker of white matter alterations in MRI-negative temporal lobe epilepsy: validation with demographic covariate adjustment

  • 期刊论文

  • 发表日期：

    2026年2月23日

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  • Suxiang Jiang,
  • Tingting Zhu,
  • Jing Wang,
  • Xianhong Lin,
  • Xiaotong Wu,
  • Jianjia Zhang,
  • Zhongxing Luo,
  • Yalei Shang,
  • Xiaowei Xu

摘要

Purpose

This study evaluated the peak width of skeletonized mean diffusivity (PSMD) as a quantitative imaging marker in patients with magnetic resonance imaging-negative (MRI-negative) temporal lobe epilepsy (TLE), accounting for age and sex effects.

Methods

This retrospective study included 34 MRI-negative TLE patients and 40 age- and sex-matched healthy controls (HCs). PSMD was calculated using tract-based spatial statistics and histogram analysis. Hierarchical regression identified PSMD determinants. Receiver operating characteristic analysis compared uncorrected and age- and sex-corrected PSMD, with the latter validated by 10-fold cross-validation.

Results

PSMD was significantly elevated in patients versus HCs (2.545 × 10−⁴ mm²/s vs. 2.340 × 10−⁴ mm²/s, p = 0.004) and independently associated with TLE (OR = 2.39, p = 0.011). Sensitivity analysis confirmed robustness (OR = 2.22, p = 0.013). In addition, males showed higher PSMD than females in both patients (p = 0.022) and HCs (p < 0.001). Furthermore, age (β = 0.453, p = 0.005) and male sex (β = 0.539, p = 0.014) were associated with higher PSMD. Age/sex correction improved specificity (82.5% vs. 67.5%) but reduced sensitivity (64.7% vs. 52.9%), with an area under the curve (AUC) of 0.696. AUC improvement was non-significant (p = 0.676); cross-validated AUC was 0.628.

Conclusion

PSMD is a quantitative marker of diffuse white matter pathology in MRI-negative TLE, modulated by demographic factors. Consistent sex effects across groups indicate biological rather than disease-specific variation. Demographic adjustment improves specificity but not overall accuracy, supporting PSMD for group-level cross-sectional studies. Sex effects must be controlled for in white-matter diffusion MRI.