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Mechanical properties of the in vivo adolescent human brain.

ABSTRACT: Viscoelastic mechanical properties of the in vivo human brain, measured noninvasively with magnetic resonance elastography (MRE), have recently been shown to be affected by aging and neurological disease, as well as relate to performance on cognitive tasks in adults. The demonstrated sensitivity of brain mechanical properties to neural tissue integrity make them an attractive target for examining the developing brain; however, to date, MRE studies on children are lacking. In this work, we characterized global and regional brain stiffness and damping ratio in a sample of 40 adolescents aged 12-14 years, including the lobes of the cerebrum and subcortical gray matter structures. We also compared the properties of the adolescent brain to the healthy adult brain. Temporal and parietal cerebral lobes were softer in adolescents compared to adults. We found that of subcortical gray matter structures, the caudate and the putamen were significantly stiffer in adolescents, and that the hippocampus and amygdala were significantly less stiff than all other subcortical structures. This study provides the first detailed characterization of adolescent brain viscoelasticity and provides baseline data to be used in studying development and pathophysiology.

SUBMITTER: McIlvain G

PROVIDER: S-EPMC6289278 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Mechanical properties of the in vivo adolescent human brain.

McIlvain Grace G Schwarb Hillary H Cohen Neal J NJ Telzer Eva H EH Johnson Curtis L CL

Developmental cognitive neuroscience 20180610

Viscoelastic mechanical properties of the in vivo human brain, measured noninvasively with magnetic resonance elastography (MRE), have recently been shown to be affected by aging and neurological disease, as well as relate to performance on cognitive tasks in adults. The demonstrated sensitivity of brain mechanical properties to neural tissue integrity make them an attractive target for examining the developing brain; however, to date, MRE studies on children are lacking. In this work, we charac ...[more]

PMID: 29906788

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue. Both pancreatitis (2.15?±?0.41?kPa, Mean?±?SD) and tumors (5.46?±?3.18?kPa) exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06?±?0.25?kPa; p?<?.005). The average viscosity of pancreatitis samples (63.2?±?26.7?kPa·s) is significantly lower than that of both normal tissue (252?±?134?kPa·s) and tumors (349?±?222?kPa·s; p?<?.005). To mimic this remodeling behavior, PDAC and TAS cells were isolated from human PDAC tumors. Conditioned medium from PDAC cells was used to culture TAS-embedded collagen hydrogels. After 7?days, TAS-embedded gels in control medium reached SSM (1.45?±?0.12?kPa) near normal pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38?±?0.146?kPa) consistent with tumors. Taken together, we have demonstrated an in vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition, our quantification of viscoelastic properties suggests that elastography algorithms incorporating viscosity may be able to more accurately distinguish between pancreatic cancer and pancreatitis. STATEMENT OF SIGNIFICANCE:Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC) is challenged by a lack of stroma-mimicking model systems. To design appropriate models, pancreatic tissue must be characterized with a method capable of evaluating in vitro models as well. Our indentation-based characterization tool quantified the distinct viscoelastic signatures of inflamed resections from pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development of mechanically appropriate engineered tissues and scaffolds. We also made progress toward a 3D in vitro system that recapitulates mechanical properties of tumors. Our in vitro model of stromal cells in collagen and complementary characterization system can be used to investigate mechanisms of cancer-stroma crosstalk in PDAC and to propose and test innovative therapies.

Dataset Information

Mechanical properties of the in vivo adolescent human brain.

Publications

Mechanical properties of the in vivo adolescent human brain.

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