Purpose

To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in normal aging and cognitive decline associated with familial Alzheimer's disease (fAD).

Materials and methods

Resting state BOLD fMRI data were acquired at 3T from two independent cohorts of subjects consisting of healthy young (age 23 ± 2 years, n = 8) and aged volunteers (age 66 ± 3 years, n = 8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2 ± 15.8 years; and eight nonmutation carrying family members, age 28.8 ± 5.9 years). Mean ApEn values were compared between the two age groups and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain.

Results

Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis.

Conclusion

ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases.

Background

Diffusion-weighted imaging has shown initial promise for evaluating response to bevacizumab in patients with high-grade glioma (HGG). However, it is well recognized that the apparent diffusion coefficient (ADC) is influenced by bevacizumab-induced reductions in edema, which may limit its prognostic value. We demonstrate that an advanced diffusion-weighted imaging technique, restriction spectrum imaging (RSI), improves the evaluation of response to bevacizumab because unlike ADC, RSI is not affected by resolution of edema.

Methods

RSI and ADC maps were analyzed for 40 patients with HGG prior to and following initiation of bevacizumab. Volumes of interest were drawn for regions of contrast enhancement (CE) and fluid attenuated inversion recovery (FLAIR) hyperintensity and histogram percentiles within volumes of interest were calculated for ADC 10th percentile (ADC-CE_10%, ADC-FLAIR_10%) and for RSI 90th percentile (RSI-CE_90%, RSI-FLAIR_90%). Cox proportional hazard models were used to evaluate the relationship between imaging parameters, progression-free survival (PFS), and overall survival (OS).

Results

An increase in RSI-FLAIR_90% following bevacizumab was the strongest predictor of poor PFS (P= .016) and OS (P= .004), whereas decreases in ADC-FLAIR_10% showed a weaker association with OS only (P= .041). Within the CE region, increases in RSI-CE_90% alone were associated with poorer OS. Correlational analysis revealed that decreases in FLAIR volume were associated with decreases in ADC-FLAIR_10%, but not with changes in RSI-FLAIR_90%.

Conclusion

RSI is less influenced by changes in edema, conferring an advantage of RSI over ADC for evaluating response to anti-angiogenic therapy in patients with HGG.