Superviscous properties of the in vivo brain at large scales

Herthum, Helge; Dempsey, Sergio C. H.; Samani, Abbas; Schrank, Felix; Shahryari, Mehrgan; Warmuth, Carsten; Tzschätzsch, Heiko; Braun, Jürgen; Sack, Ingolf

doi:10.1016/j.actbio.2020.12.027

Cited by 21 publications

(10 citation statements)

References 76 publications

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“…This prompts the term liquid-liver phantom, although, clearly, the liver is not a liquid. Nevertheless, the fact that the phantom behaves as a liquid at static load, while fitting literature data for solid-liver properties above 30 Hz, indicates a superviscous material behavior similar to that recently reported for human brain 44 …”

Section: Discussionsupporting

confidence: 83%

“…Nevertheless, the fact that the phantom behaves as a liquid at static load, while fitting literature data for solid-liver properties above 30 Hz, indicates a superviscous material behavior similar to that recently reported for human brain. 44 It is a salient finding of our study that the phantom can be produced reproducibly, with only 0.5% variability, and thus fulfills the QIBA requirements of 5%. 42 The increase of 4%/6 months in stiffness due to aging of the phantom material is as well within the QIBA requirements of less than 5% per 6 months.…”

Section: Discussionmentioning

confidence: 53%

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Liquid-Liver Phantom

Morr¹,

Herthum

Schrank³

et al. 2022

Invest Radiol

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Objectives: Tissue stiffness can guide medical diagnoses and is exploited as an imaging contrast in elastography. However, different elastography devices show different liver stiffness values in the same subject, hindering comparison of values and establishment of system-independent thresholds for disease detection. There is a need for standardized phantoms that specifically address the viscosity-related dispersion of stiffness over frequency. To improve standardization of clinical elastography across devices and platforms including ultrasound and magnetic resonance imaging (MRI), a comprehensively characterized phantom is introduced that mimics the dispersion of stiffness of the human liver and can be generated reproducibly. Materials and Methods: The phantom was made of linear polymerized polyacrylamide (PAAm) calibrated to the viscoelastic properties of healthy human liver in vivo as reported in the literature. Stiffness dispersion was analyzed using the 2-parameter springpot model fitted to the dispersion of shear wave speed of PAAm, which was measured by shear rheometry, ultrasound-based time-harmonic elastography, clinical magnetic resonance elastography (MRE), and tabletop MRE in the frequency range of 5 to 3000 Hz. Imaging parameters for ultrasound and MRI, reproducibility, aging behavior, and temperature dependency were assessed. In addition, the frequency bandwidth of shear wave speed of clinical elastography methods (Aplio i900, Canon; Acuson Sequoia, Siemens; FibroScan, EchoSense) was characterized. Results: Within the entire frequency range analyzed in this study, the PAAm phantom reproduced well the stiffness dispersion of human liver in vivo despite its fluid properties under static loading (springpot stiffness parameter, 2.14 [95% confidence interval, 2.08-2.19] kPa; springpot powerlaw exponent, 0.367 [95% confidence interval, 0.362-0.373]). Imaging parameters were close to those of liver in vivo with only slight variability in stiffness values of 0.5% (0.4%, 0.6%), 4.1% (3.9%, 4.5%), and −0.63% (−0.67%, −0.58%), respectively, between batches, over a 6-month period, and per °C increase in temperature. Conclusions: The liquid-liver phantom has useful properties for standardization and development of liver elastography. First, it can be used across clinical and experimental elastography devices in ultrasound and MRI. Second, being a liquid, it can easily be adapted in size and shape to specific technical requirements, and by adding inclusions and scatterers. Finally, because the phantom is based on noncrosslinked linear PAAm constituents, it is easy to produce, indicating potential widespread use among researchers and vendors to standardize liver stiffness measurements.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 53%

Liquid-Liver Phantom

Morr¹,

Herthum

Schrank³

et al. 2022

Invest Radiol

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“…Brain tissue is a multiscale compound material with superviscous anomalous viscous properties at the length scales that are typically investigated by MRE. 43 Therefore, a large dispersion of viscoelastic constants is expected within a relatively small dynamic range from 1 to 20 Hz, in which shear modulus values increase by more than an order of magnitude. 43 A similarly strong viscoelastic dispersion is expected for brain tumors.…”

Section: Discussionmentioning

confidence: 99%

“…43 Therefore, a large dispersion of viscoelastic constants is expected within a relatively small dynamic range from 1 to 20 Hz, in which shear modulus values increase by more than an order of magnitude. 43 A similarly strong viscoelastic dispersion is expected for brain tumors. 17,30 Therefore, it is not surprising that we observed quantitative differences in the material constants measured by MRE and OS.…”

Section: Discussionmentioning

confidence: 99%

Whole tissue and single cell mechanics are correlated in human brain tumors

Sauer¹,

Fritsch

Grosser³

et al. 2021

Soft Matter

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“…However, this curl-analysis did not provide more consistent values than our standard MDEV inversion with respect to confidence intervals and statistical power. Finally, 2D brain MRE has a long tradition in disease detection (Wuerfel et al, 2010;Streitberger et al, 2012Streitberger et al, , 2017Streitberger et al, , 2020Lipp et al, 2013Lipp et al, , 2018Fehlner et al, 2016;Gerischer et al, 2018) as well as in the study of brain physiology (Sack et al, 2009(Sack et al, , 2011Schrank et al, 2020b;Herthum et al, 2021). It remains to be determined whether single-frequency 3D MRE can provide similarly consistent clinical and physiological brain data.…”

Section: Physiological Effects Of Vm On Cerebral Blood Flow Icp and Mrementioning

confidence: 99%

Real-Time Multifrequency MR Elastography of the Human Brain Reveals Rapid Changes in Viscoelasticity in Response to the Valsalva Maneuver

Herthum

Shahryari

Tzschätzsch

et al. 2021

Front. Bioeng. Biotechnol.

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Modulation of cerebral blood flow and vascular compliance plays an important role in the regulation of intracranial pressure (ICP) and also influences the viscoelastic properties of brain tissue. Therefore, magnetic resonance elastography (MRE), the gold standard for measuring in vivo viscoelasticity of brain tissue, is potentially sensitive to cerebral autoregulation. In this study, we developed a multifrequency MMRE technique that provides serial maps of viscoelasticity at a frame rate of nearly 6 Hz without gating, i.e., in quasi-real time (rt-MMRE). This novel method was used to monitor rapid changes in the viscoelastic properties of the brains of 17 volunteers performing the Valsalva maneuver (VM). rt-MMRE continuously sampled externally induced vibrations comprising three frequencies of 30.03, 30.91, and 31.8 Hz were over 90 s using a steady-state, spiral-readout gradient-echo sequence. Data were processed by multifrequency dual elasto-visco (MDEV) inversion to generate maps of magnitude shear modulus | G∗| (stiffness) and loss angle φ at a frame rate of 5.4 Hz. As controls, the volunteers were examined to study the effects of breath-hold following deep inspiration and breath-hold following expiration. We observed that | G∗| increased while φ decreased due to VM and, less markedly, due to breath-hold in inspiration. Group mean VM values showed an early overshoot of | G∗| 2.4 ± 1.2 s after the onset of the maneuver with peak values of 6.7 ± 4.1% above baseline, followed by a continuous increase in stiffness during VM. A second overshoot of | G∗| occurred 5.5 ± 2.0 s after the end of VM with peak values of 7.4 ± 2.8% above baseline, followed by 25-s sustained recovery until the end of image acquisition. φ was constantly reduced by approximately 2% during the entire VM without noticeable peak values. This is the first report of viscoelasticity changes in brain tissue induced by physiological maneuvers known to alter ICP and detected by clinically applicable rt-MMRE. Our results show that apnea and VM slightly alter brain properties toward a more rigid-solid behavior. Overshooting stiffening reactions seconds after onset and end of VM reveal rapid autoregulatory processes of brain tissue viscoelasticity.

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Superviscous properties of the in vivo brain at large scales

Cited by 21 publications

References 76 publications

Liquid-Liver Phantom

Liquid-Liver Phantom

Whole tissue and single cell mechanics are correlated in human brain tumors

Real-Time Multifrequency MR Elastography of the Human Brain Reveals Rapid Changes in Viscoelasticity in Response to the Valsalva Maneuver

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