Mapping brain mechanical property maturation from childhood to adulthood

McIlvain, Grace; Schneider, Julie; Matyi, Melanie A.; McGarry, Matthew; Qi, Zhenghan; Spielberg, Jeffrey M.; Johnson, Curtis L.

doi:10.1016/j.neuroimage.2022.119590

Cited by 22 publications

(13 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Much less is known about periods of brain development and maturation. Several studies have reported global stiffness to be generally consistent with age in children, adolescents, and young adults (McIlvain et al., 2018; Ozkaya et al., 2021; Yeung et al., 2019), though a recent study on a large sample found instead lower stiffness and higher damping ratio with increasing age from 5 to 35 years (McIlvain et al., 2022). This is in contrast to rodent brain MRE studies that have reported increased stiffness and either decreased or unchanged phase angle (comparable to damping ratio) with age (Guo et al., 2019; Schregel et al., 2012), though with regional differences in both magnitude and direction of age‐related property change.…”

Section: Discussionmentioning

confidence: 98%

“…This is most clearly observed in measures of the corpus callosum, where all groups increased in stiffness and damping ratio between adolescence and adulthood, with differences in degree of change occurring based on postnatal treatment or intervention condition. The effects of aging on brain mechanical properties in adulthood are well-known (Hiscox et al, 2021), with lower stiffness (Arani et al, 2015;Hiscox et al, 2018;Sack et al, 2011), and higher damping ratio (Delgorio et al, 2021) Ozkaya et al, 2021;Yeung et al, 2019), though a recent study on a large sample found instead lower stiffness and higher damping ratio with increasing age from 5 to 35 years (McIlvain et al, 2022). This is in contrast to rodent brain MRE studies that have reported increased stiffness and either decreased or unchanged phase angle (comparable to damping ratio) with age (Guo et al, 2019;Schregel et al, 2012), though with regional differences in both magnitude and direction of age-related property change.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders

Milbocker,

Williams,

Caban‐Rivera

et al. 2024

Alcohol, Clinical and Experimental Research

View full text Add to dashboard Cite

BackgroundFetal alcohol spectrum disorders (FASD), a group of prevalent conditions resulting from prenatal alcohol exposure, affect the maturation of cerebral white matter as first identified with neuroimaging. However, traditional methods are unable to track subtle microstructural alterations to white matter. This preliminary study uses a highly sensitive and clinically translatable magnetic resonance elastography (MRE) protocol to assess brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD.MethodsFemale rat pups were either alcohol‐exposed (AE) via intragastric intubation of alcohol in milk substitute (5.25 g/kg/day) or sham‐intubated (SI) on postnatal days (PD) four through nine to model alcohol exposure during the brain growth spurt. On PD 30, half of AE and SI rats were randomly assigned to either a wheel‐running or standard cage for 12 days. Magnetic resonance elastography was used to measure whole brain and callosal mechanical properties at the end of the intervention (around PD 42) and at 1 month post‐intervention, and findings were validated with histological quantification of oligoglia.ResultsAlcohol exposure reduced forebrain stiffness (p = 0.02) in standard‐housed rats. The adolescent exercise intervention mitigated this effect, confirming that increased aerobic activity supports proper neurodevelopmental trajectories. Forebrain damping ratio was lowest in standard‐housed AE rats (p < 0.01), but this effect was not mitigated by intervention exposure. At 1 month post‐intervention, all rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Callosal stiffness and damping ratio increased with age. With cessation of exercise, there was a negative rebound effect on the quantity of callosal oligodendrocytes, irrespective of treatment group, which diverged from our MRE results.ConclusionsThis is the first application of MRE to measure the brain's mechanical properties in a rodent model of FASD. MRE successfully captured alcohol‐related changes in forebrain stiffness and damping ratio. Additionally, MRE identified an exercise‐related increase to forebrain stiffness in AE rats.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders

Milbocker,

Williams,

Caban‐Rivera

et al. 2024

Alcohol, Clinical and Experimental Research

View full text Add to dashboard Cite

show abstract

“…During development, synaptic pruning of neural connections can cause a decline in gray matter volume (Gennatas et al, 2017), which occurs while myelination in the brain is increasing (Mabbott et al, 2006). Interestingly, we recently reported that brain stiffness appears to decrease from childhood to early adulthood (McIlvain, Schneider, et al, 2022). During normal adult aging, the brain undergoes a variety of degenerative changes, including decreases in the density of neurons, breakdown of myelin integrity, and the appearance of white matter lesions (Guttmann et al, 1998;Terry et al, 1987;Vernooij et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Data collected at UIUC was previously pooled and used to create a standard-space atlas of brain mechanical properties . Additional data included in this work has been reported, in part, in several previous publications (Delgorio et al, 2022(Delgorio et al, , 2023McIlvain, Schneider, et al, 2022;Sanjana et al, 2021;Schneider et al, 2022). Readers are referred to prior works for additional information.…”

Section: Participantsmentioning

confidence: 99%

Mechanical Property Based Brain Age Prediction using Convolutional Neural Networks

Clements

Claros-Olivares

McIlvain

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Brain age is a quantitative estimate to explain an individual's structural and functional brain measurements relative to the overall population and is particularly valuable in describing differences related to developmental or neurodegenerative pathology. Accurately inferring brain age from brain imaging data requires sophisticated models that capture the underlying age-related brain changes. Magnetic resonance elastography (MRE) is a phase contrast MRI technology that uses external palpations to measure brain mechanical properties. Mechanical property measures of viscoelastic shear stiffness and damping ratio have been found to change across the entire life span and to reflect brain health due to neurodegenerative diseases and even individual differences in cognitive function. Here we develop and train a multi-modal 3D convolutional neural network (CNN) to model the relationship between age and whole brain mechanical properties. After training, the network maps the measurements and other inputs to a brain age prediction. We found high performance using the 3D maps of various mechanical properties to predict brain age. Stiffness maps alone were able to predict ages of the test group subjects with a mean absolute error (MAE) of 3.76 years, which is comparable to single inputs of damping ratio (MAE: 3.82) and outperforms single input of volume (MAE: 4.60). Combining stiffness and volume in a multi-modal approach performed the best, with an MAE of 3.60 years, whereas including damping ratio worsened model performance. Our results reflect previous MRE literature that had demonstrated that stiffness is more strongly related to chronological age than damping ratio. This machine learning model provides the first prediction of brain age from brain biomechanical data - an advancement towards sensitively describing brain integrity differences in individuals with neuropathology.

show abstract

“…Much less is known about periods of brain development and maturation. Several studies have reported global stiffness to be generally consistent with age in children, adolescents, and young adults (McIlvain et al, 2018; Ozkaya et al, 2021; Yeung et al, 2019), though a recent study on a large sample found instead lower stiffness and higher damping ratio with increasing age from 5 to 35 years (McIlvain et al, 2022). This is in contrast to rodent brain MRE studies that have reported increased stiffness and either decreased or unchanged phase angle (comparable to damping ratio) with age (Guo 2019, Schregel 2012), though with regional differences in both magnitude and direction of age-related property change.…”

Section: Discussionmentioning

confidence: 99%

Monitoring lasting changes to brain tissue integrity through mechanical properties following adolescent exercise intervention in a rat model of Fetal Alcohol Spectrum Disorders

Milbocker,

Williams,

Caban-Rivera

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundFetal Alcohol Spectrum Disorders (FASD) encompass a group of highly prevalent conditions resulting from prenatal alcohol exposure. Alcohol exposure during the third trimester of pregnancy overlapping with the brain growth spurt is detrimental to white matter growth and myelination, particularly in the corpus callosum, ultimately affecting tissue integrity in adolescence. Traditional neuroimaging techniques have been essential for assessing neurodevelopment in affected youth; however, these methods are limited in their capacity to track subtle microstructural alterations to white matter, thus restricting their effectiveness in monitoring therapeutic intervention. In this preliminary study we use a highly sensitive and clinically translatable Magnetic Resonance Elastography (MRE) protocol for assessing brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD.MethodsRat pups were divided into two groups: alcohol-exposed (AE) pups which received alcohol in milk substitute (5.25 g/kg/day) via intragastric intubation on postnatal days (PD) four through nine during the rat brain growth spurt (Dobbing and Sands, 1979), or sham-intubated (SI) controls. In adolescence, on PD 30, half AE and SI rats were randomly assigned to either a modified home cage with free access to a running wheel or to a new home cage for 12 days (Gursky and Klintsova, 2017). Previous studies conducted in the lab have shown that 12 days of voluntary exercise intervention in adolescence immediately ameliorated callosal myelination in AE rats (Milbocker et al., 2022, 2023). MRE was used to measure longitudinal changes to mechanical properties of the whole brain and the corpus callosum at intervention termination and one-month post-intervention. Histological quantification of precursor and myelinating oligoglia in corpus callosum was performed one-month post-intervention.ResultsPrior to intervention, AE rats had lower forebrain stiffness in adolescence compared to SI controls (p= 0.02). Exercise intervention immediately mitigated this effect in AE rats, resulting in higher forebrain stiffness post-intervention in adolescence. Similarly, we discovered that forebrain damping ratio was lowest in AE rats in adolescence (p< 0.01), irrespective of intervention exposure. One-month post-intervention in adulthood, AE and SI rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Taken together, these MRE data suggest that adolescent exercise intervention supports neurodevelopmental “catch-up” in AE rats. Analysis of the stiffness and damping ratio of the body of corpus callosum revealed that these measures increased with age. Finally, histological quantification of myelinating oligodendrocytes one-month post-intervention revealed a negative rebound effect of exercise cessation on the total estimate of these cells in the body of corpus callosum, irrespective of treatment group which was not convergent with noninvasive MRE measures.ConclusionsThis is the first application of MRE to measure changes in brain mechanical properties in a rodent model of FASD. MRE successfully captured alcohol-related changes to forebrain stiffness and damping ratio in adolescence. These preliminary findings expand upon results from previous studies which used traditional diffusion neuroimaging to identify structural changes to the adolescent brain in rodent models of FASD (Milbocker et al., 2022; Newville et al., 2017). Additionally,in vivoMRE identified an exercise-related alteration to forebrain stiffness that occurred in adolescence, immediately post-intervention.

show abstract

Mapping brain mechanical property maturation from childhood to adulthood

Cited by 22 publications

References 83 publications

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders

Mechanical Property Based Brain Age Prediction using Convolutional Neural Networks

Monitoring lasting changes to brain tissue integrity through mechanical properties following adolescent exercise intervention in a rat model of Fetal Alcohol Spectrum Disorders

Contact Info

Product

Resources

About