Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer's disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.
Motivation: There exists a need for a comprehensive method to analyze regional brain tissue mechanics that accounts for variability across subject populations. Goal(s): Here we aimed to implement a multivariate data-driven technique to capture brain mechanical properties across a wide population while preserving small-scale differences between subjects. Approach: Non-negative matrix factorization was used to reduce mechanical properties derived from magnetic resonance elastography (MRE) into a low-dimensional form to generate unconfined regions of the brain that demonstrate high covariance across all subjects. Results: This technique was able to capture recognizable anatomical regions in the brain without structural input to determine weightings on the population average. Impact: This low-dimensional representation of brain tissue mechanics acquired from non-negative matrix factorization and MRE will help define baseline properties that accurately represent a wide range of subject populations while minimizing variability across imaging studies and contributing to improved statistical models.
The aim of this study was to determine whether magnetic resonance elastography (MRE) could sensitively detect mechanical property alterations in the hippocampal subfields due to amnestic mild cognitive impairment (aMCI) - a prodromal stage of Alzheimer’s disease (AD). Results show that entorhinal cortex viscoelasticity was significantly lower in aMCI participants. Further, the entorhinal cortex did not display significant volume differences due to aMCI, which demonstrates how MRE may yield more information about the health of a region known to harbor AD pathology. These results suggest that hippocampal subfield MRE measures show potential for use as an imaging biomarker of disease.
Magnetic resonance elastography (MRE) is a robust and sensitive tool used to measure brain mechanical properties that can accurately detect improvements in brain health and function. Exercise and aerobic fitness levels are strongly tied to these brain mechanical properties and their related functionality. In healthy older adults, greater fitness is associated with better memory and increased mechanical integrity of the brain. In a population of older adults with mild cognitive impairment, there is a notable decrease in memory function and aerobic fitness compared to healthy controls, and this decrease is measurable in the mechanical properties of the brain using MRE.
Abstract Background Magnetic resonance elastography (MRE) is an MRI technique that uses mild, externally applied vibrations to quantify the mechanical properties of tissues in vivo. MRE measures, such as stiffness, have been shown to be sensitive to changes in brain health with aging and neurodegeneration. Here we used MRE to characterize differences in brain mechanical properties between individuals with amnestic mild cognitive impairment (aMCI) and cognitively unimpaired subjects (CU). Method A cohort of 67 cognitively unimpaired subjects (21M/46F; 60‐82y) and a cohort of 34 subjects with aMCI (11M/23F; 60‐89y) completed an MRE scan to assess their brain mechanical properties. From this, we quantified basal ganglia (BG) stiffness in each subject including the caudate, pallidum, putamen, and nucleus accumbens. Subjects also completed the NIH toolbox cognition battery from which we examined fluid cognition composite score, which reflects logic and reasoning skills. Result We found a significant group difference in stiffness of the basal ganglia (BG). Interestingly, aMCI subjects had significantly higher BG stiffness than CUs (2.99 vs. 2.89 kPa, p<0.05; Figure 1). Within the aMCI group, BG stiffness was positively correlated with fluid cognitive score (r=0.48, p<0.01; Figure 2), where higher scores were associated with greater stiffness; the same relationship in the CU group was not statistically significant. Conclusion Higher BG stiffness found in the aMCI group may reflect aspects of aMCI pathology and progression that MRE can sensitively detect. Most MRE studies report that healthy brains are associated with higher stiffness than those with neurodegenerative pathology, with our previous work showing that aMCI participants had softer hippocampi than age‐matched CUs (Delgorio, 2023). Our findings in the BG are surprising in this context but may indicate a compensatory mechanism that occurs during early progression of aMCI and results in increased stiffness, which was previously suggested by Murphy (2016). Here we also provide the first evidence that higher BG stiffness in aMCI is associated with better cognitive function, which further points to higher stiffness being compensatory rather than pathological. The neurobiological basis of this compensatory increase in BG stiffness of aMCI subjects requires further study but could be influenced by acute neuroinflammatory processes.
This study tested the utility of high-resolution magnetic resonance elastography (MRE) to analyze frontal cortex degradation due to advancing age. Brain tissue stiffness significantly varied in frontal cortex regions and frontal cortex stiffness also significantly decreased with age. A significant interaction between age and region was found, indicating regions changed differently with age. The stiffness of all frontal cortex regions degraded more per year than reported whole frontal lobe stiffness loss, indicating greater loss in the cortex with age. This approach brings potentially increased sensitivity and specificity to the structure-function relationship found in the frontal cortex with age.
Abstract Background Magnetic resonance elastography (MRE) is an MRI technique that uses mild, externally applied vibrations to quantify the mechanical properties of tissues in vivo. MRE measures, such as stiffness, have been shown to be sensitive to changes in brain health with aging and neurodegeneration. Here we used MRE to characterize differences in brain mechanical properties between individuals with amnestic mild cognitive impairment (aMCI) and cognitively unimpaired subjects (CU). Method A cohort of 67 cognitively unimpaired subjects (21M/46F; 60‐82y) and a cohort of 34 subjects with aMCI (11M/23F; 60‐89y) completed an MRE scan to assess their brain mechanical properties. From this, we quantified basal ganglia (BG) stiffness in each subject including the caudate, pallidum, putamen, and nucleus accumbens. Subjects also completed the NIH toolbox cognition battery from which we examined fluid cognition composite score, which reflects logic and reasoning skills. Result We found a significant group difference in stiffness of the basal ganglia (BG). Interestingly, aMCI subjects had significantly higher BG stiffness than CUs (2.99 vs. 2.89 kPa, p<0.05; Figure 1). Within the aMCI group, BG stiffness was positively correlated with fluid cognitive score (r = 0.48, p<0.01; Figure 2), where higher scores were associated with greater stiffness; the same relationship in the CU group was not statistically significant. Conclusion Higher BG stiffness found in the aMCI group may reflect aspects of aMCI pathology and progression that MRE can sensitively detect. Most MRE studies report that healthy brains are associated with higher stiffness than those with neurodegenerative pathology, with our previous work showing that aMCI participants had softer hippocampi than age‐matched CUs (Delgorio, 2023). Our findings in the BG are surprising in this context but may indicate a compensatory mechanism that occurs during early progression of aMCI and results in increased stiffness, which was previously suggested by Murphy (2016). Here we also provide the first evidence that higher BG stiffness in aMCI is associated with better cognitive function, which further points to higher stiffness being compensatory rather than pathological. The neurobiological basis of this compensatory increase in BG stiffness of aMCI subjects requires further study but could be influenced by acute neuroinflammatory processes.
Motivation: Magnetic resonance elastography (MRE) sensitively captures structural changes in the brain. However, application of this technique has been limited to cross-sectional studies in adolescents. Goal(s): Our aim was to examine, for the first time, longitudinal changes in MRE-derived brain tissue mechanical properties during adolescence. Approach: Shear stiffness and damping ratio were calculated for 14 adolescents during two study visits separated by a year. Results: Stiffness significantly decreased over one year. The largest stiffness declines were in subcortical gray matter, in agreement with cross-sectional studies. Changes in both shear stiffness and damping ratio were correlated with progression of puberty. Impact: This longitudinal study found wide-spread softening of brain tissue during adolescence, supporting cross-sectional findings. These changes were also correlated with the progression of puberty. This confirms the sensitivity of mechanical properties to capture structural changes of brain maturation.
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