In vivo time-harmonic ultrasound elastography of the human brain detects acute cerebral stiffness changes induced by intracranial pressure variations

Abstract

Cerebral stiffness (CS) reflects the biophysical environment in which neurons grow and function. While long-term CS changes can occur in the course of chronic neurological disorders and aging, little is known about acute variations of CS induced by intracranial pressure variations. Current gold standard methods for CS and intracranial pressure such as magnetic resonance elastography and direct pressure recordings are either expensive and slow or invasive. The study objective was to develop a real-time method for in vivo CS measurement and to demonstrate its sensitivity to physiological aging and intracranial pressure variations induced by the Valsalva maneuver in healthy volunteers. We used trans-temporal ultrasound time-harmonic elastography (THE) with external shear-wave stimulation by continuous and superimposed vibrations in the frequency range from 27 to 56 Hz. Multifrequency wave inversion generated maps of shear wave speed (SWS) as a surrogate maker of CS. On average, cerebral SWS was 1.56 ± 0.08 m/s with a tendency to reduce with age (R = −0.76, p < 0.0001) while Valsalva maneuver induced an immediate stiffening of the brain as reflected by a 10.8 ± 2.5% increase (p < 0.0001) in SWS. Our results suggest that CS is tightly linked to intracranial pressure and might be used in the future as non-invasive surrogate marker for intracranial pressure, which otherwise requires invasive measurements.

Cardiac-gated steady-state multifrequency magnetic resonance elastography of the brain: Effect of cerebral arterial pulsation on brain viscoelasticity

“…It is worthwhile to note that our present study is not in conflict with previous studies reporting a positive correlation between brain stiffness and ICP or perfusion pressure. 28,29,37 As outlined above, we believe that our technique is insensitive to short-term transient tissue compression induced by CAP, while static changes in the effective compression modulus of the brain, e.g. related to hypercapnia or the Valsalva maneuver, could impact MRE values differently from the effect we report here.…”

Cerebral Ultrasound Time-Harmonic Elastography Reveals Softening of the Human Brain Due to Dehydration

“…Similarly, experimentally induced hypercapnia was associated with a synchronous increase in cerebral blood flow and CS, as revealed by MRE ( Hetzer et al, 2019 ) and THE ( Kreft et al, 2020 ). Previous work also revealed that the Valsalva maneuver causes an increase in CS on a short time scale in the order of seconds ( Tzschatzsch et al, 2018 ). Taken together, this previous evidence suggests that lower cerebral blood flow, as a result of dehydration, reduces CS, which is consistent with the observations made in our study.…”

“…In this study, we investigate the effect of dehydration on CS using cerebral time-harmonic elastography (THE), which utilizes multifrequency vibrations induced in the brain by an external driver in combination with transtemporal ultrasound ( Tzschatzsch et al, 2018 ). Cerebral THE has several advantages over MRE such as being available at the bedside and providing instantaneous feedback, which facilitates identification of rapid CS changes.…”

MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus

“…These diverging reports highlight the complex nature of hydrocephalus; e.g. cytopathology such as periventricular edema and dysmyelination which may drive decreased stiffness ( Del Bigio et al, 2003 , Del Bigio, 2010 ), while elevated pressure, which can be intermittent but chronic in NPH, may drive increased stiffness ( Pong et al, 2017 , Tzschatzsch et al, 2018 ).…”