Andreas Fehlner

Towards an elastographic atlas of brain anatomy.

Cerebral viscoelastic constants can be measured in a noninvasive, image-based way by magnetic resonance elastography (MRE) for the detection of neurological disorders. However, MRE brain maps of viscoelastic constants are still limited by low spatial resolution. Here we introduce three-dimensional multifrequency MRE of the brain combined with a novel reconstruction algorithm based on a model-free multifrequency inversion for calculating spatially resolved viscoelastic parameter maps of the human brain corresponding to the dynamic range of shear oscillations between 30 and 60 Hz. Maps of two viscoelastic parameters, the magnitude and the phase angle of the complex shear modulus, |G*| and φ, were obtained and normalized to group templates of 23 healthy volunteers in the age range of 22 to 72 years. This atlas of the anatomy of brain mechanics reveals a significant contrast in the stiffness parameter |G*| between different anatomical regions such as white matter (WM; 1.252±0.260 kPa), the corpus callosum genu (CCG; 1.104±0.280 kPa), the thalamus (TH; 1.058±0.208 kPa) and the head of the caudate nucleus (HCN; 0.649±0.101 kPa). φ, which is sensitive to the lossy behavior of the tissue, was in the order of CCG (1.011±0.172), TH (1.037±0.173), CN (0.906±0.257) and WM (0.854±0.169). The proposed method provides the first normalized maps of brain viscoelasticity with anatomical details in subcortical regions and provides useful background data for clinical applications of cerebral MRE.

Cerebral magnetic resonance elastography in supranuclear palsy and idiopathic Parkinson's disease

Detection and discrimination of neurodegenerative Parkinson syndromes are challenging clinical tasks and the use of standard T1- and T2-weighted cerebral magnetic resonance (MR) imaging is limited to exclude symptomatic Parkinsonism. We used a quantitative structural MR-based technique, MR-elastography (MRE), to assess viscoelastic properties of the brain, providing insights into altered tissue architecture in neurodegenerative diseases on a macroscopic level. We measured single-slice multifrequency MRE (MMRE) and three-dimensional MRE (3DMRE) in two neurodegenerative disorders with overlapping clinical presentation but different neuropathology — progressive supranuclear palsy (PSP: N = 16) and idiopathic Parkinsons disease (PD: N = 18) as well as in controls (N = 18). In PSP, both MMRE (Δμ = − 28.8%, Δα = − 4.9%) and 3DMRE (Δ|G*|: − 10.6%, Δφ: − 34.6%) were significantly reduced compared to controls, with a pronounced reduction within the lentiform nucleus (Δμ = − 34.6%, Δα = − 8.1%; Δ|G*|: − 7.8%, Δφ: − 44.8%). MRE in PD showed a comparable pattern, but overall reduction in brain elasticity was less severe reaching significance only in the lentiform nucleus (Δμ n.s., Δα = − 7.4%; Δ|G*|: − 6.9%, Δφ: n.s.). Beyond that, patients showed a close negative correlation between MRE constants and clinical severity. Our data indicate that brain viscoelasticity in PSP and PD is differently affected by the underlying neurodegeneration; whereas in PSP all MRE constants are reduced and changes in brain softness (reduced μ and |G*|) predominate those of viscosity (α and φ) in PD.

Higher-resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome

To assess if higher‐resolution magnetic resonance elastography (MRE) is a technique that can measure the in vivo mechanical properties of brain tissue and is sensitive to early signatures of brain tissue degradation in patients with clinically isolated syndrome (CIS).

Measurement of in vivo cerebral volumetric strain induced by the Valsalva maneuver.

Compressibility of biological tissues such as brain parenchyma is related to its poroelastic nature characterized by the geometry and pressure of vasculature and interconnected fluid-filled spaces. Thus, cerebral volumetric strain may be sensitive to intracranial pressure which can be altered under physiological conditions. So far volumetric strain has attained little attention in studies of the mechanical behavior of the brain. This paper reports a study of measuring the in vivo cerebral volumetric strain induced by the Valsalva maneuver (VM) where forced expiration against a closed glottis leads to a transient increase in the intracranial pressure. For this purpose we applied three-dimensional magnetic resonance imaging equipped with a patient-controlled acquisition system to five healthy volunteers. With each volunteer, three experiments were performed: one with VM and two in resting state. i.e. normal ventilation, which were conducted before and after VM. The VM data were registered to reference data by morphology based non-rigid deformation, yielding 3D maps of total displacements and volumetric strain. On average, VM induced volumetric strain correlated to whole-brain dilatation of -3.14±0.87% and -2.80±0.71% compared to the reference states before and after VM, respectively. These values were well reproduced by repetitive experiments during the same scan as well as by repeated measurements in one volunteer on different days. Combined with literature data of intracranial pressure changes, our volumetric strain values can be used to elucidate the static compression modulus of the in vivo human brain. These results add knowledge to the understanding of the brain׳s biomechanical properties under physiological conditions.

Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves

The aim of this study was to introduce remote wave excitation for high‐resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25–45‐Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase φ of the complex shear modulus were reconstructed using multifrequency dual elasto‐visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set‐up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high‐resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 ± 0.08 kPa) and decreased within the corticospinal tract in the caudal–cranial direction from the crus cerebri (1.64 ± 0.26 kPa) to the capsula interna (1.29 ± 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic. Copyright

Perfusion alters stiffness of deep gray matter

Viscoelastic properties of the brain reflect tissue architecture at multiple length scales. However, little is known about the relation between vital tissue functions, such as perfusion, and the macroscopic mechanical properties of cerebral tissue. In this study, arterial spin labelling is paired with magnetic resonance elastography to investigate the relationship between tissue stiffness and cerebral blood flow (CBF) in the in vivo human brain. The viscoelastic modulus, |G*|, and CBF were studied in deep gray matter (DGM) of 14 healthy male volunteers in the following sub-regions: putamen, nucleus accumbens, hippocampus, thalamus, globus pallidus, and amygdala. CBF was further normalized by vessel area data to obtain the flux rate q which is proportional to the perfusion pressure gradient. The striatum (represented by putamen and nucleus accumbens) was distinct from the other DGM regions by displaying markedly higher stiffness and perfusion values. q was a predictive marker for DGM stiffness as analyzed by linear regression |G*| = q·(4.2 ± 0.6)kPa·s + (0.80 ± 0.06)kPa (R2 = 0.92, P = 0.006). These results suggest a high sensitivity of MRE in DGM to perfusion pressure. The distinct mechano-vascular properties of striatum tissue, as compared to the rest of DGM, may reflect elevated perfusion pressure, which could explain the well-known susceptibility of the putamen to hemorrhages.

In vivo multifrequency magnetic resonance elastography of the human intervertebral disk.

To test in vivo magnetic resonance elastography (MRE) of the human intervertebral disk (IVD).

Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions

To improve the resolution of elasticity maps by adapting motion and distortion correction methods for phase‐based magnetic resonance imaging (MRI) contrasts such as magnetic resonance elastography (MRE), a technique for measuring mechanical tissue properties in vivo.

Heterogeneous multifrequency direct inversion (HMDI) for magnetic resonance elastography with application to a clinical brain exam

HIGHLIGHTSA novel, homogeneity accommodating direct inversion method for elastographic wave inversion (HMDI) is introduced and applied to Magnetic Resonance Elastography (MRE) data.Multifrequency MRE is combined with SPM in a fully automated processing pipeline to obtain whole brain and white matter model‐free stiffness and dispersion estimates.The automatic elastograms show sharp boundaries and spatially resolved brain features without masking, median filtering or smoothing.Two multifrequency MRE methods (HMDI and MDEV) are compared on a prospective 48‐subject data set.Both methods are sensitive to known age effects and internally consistent across frequencies. ABSTRACT A new viscoelastic wave inversion method for MRE, called Heterogeneous Multifrequency Direct Inversion (HMDI), was developed which accommodates heterogeneous elasticity within a direct inversion (DI) by incorporating first‐order gradients and combining results from a narrow band of multiple frequencies. The method is compared with a Helmholtz‐type DI, Multifrequency Dual Elasto‐Visco inversion (MDEV), both on ground‐truth Finite Element Method simulations at varied noise levels and a prospective in vivo brain cohort of 48 subjects ages 18–65. In simulated data, MDEV recovered background material within 5% and HMDI within 1% of prescribed up to SNR of 20 dB. In vivo HMDI and MDEV were then combined with segmentation from SPM to create a fully automated “brain palpation” exam for both whole brain (WB), and brain white matter (WM), measuring two parameters, the complex modulus magnitude |G*|, which measures tissue “stiffness”, and the slope of |G*| values across frequencies, a measure of viscous dispersion. |G*| values for MDEV and HMDI were comparable to the literature (for a 3‐frequency set centered at 50 Hz, WB means were 2.17 and 2.15 kPa respectively, and WM means were 2.47 and 2.49 kPa respectively). Both methods showed moderate correlation to age in both WB and WM, for both |G*| and |G*| slope, with Pearsons r≥0.4 in the most sensitive frequency sets. In comparison to MDEV, HMDI showed better preservation of recovered target shapes, more noise‐robustness, and stabler recovery values in regions with rapid property change, however summary statistics for both methods were quite similar. By eliminating homogeneity assumptions within a fast, fully automatic, regularization‐free direct inversion, HMDI appears to be a worthwhile addition to the MRE image reconstruction repertoire. In addition to supporting the literature showing decrease in brain viscoelasticity with age, our work supports a wide range of inter‐individual variation in brain MRE results.

Progressive supranuclear palsy and idiopathic Parkinson’s disease are associated with local reduction of in vivo brain viscoelasticity

ObjectivesTo apply three-dimensional multifrequency MR-elastography (3DMRE) for the measurement of local cerebral viscoelasticity changes in patients with Parkinsons disease (PD) and progressive supranuclear palsy (PSP).MethodsT1-weighted anatomical imaging and 3DMRE were performed in 17 PD and 20 PSP patients as well as 12 controls. Two independent viscoelasticity parameters, |G*| and φ, were reconstructed combining seven harmonic vibration frequencies (30–60 Hz). Spatially averaged values were compared by one-way ANOVA, groups were compared using unpaired t test and Mann-Whitney test, respectively. Correlation between clinical data and parameters of brain elasticity and volume were calculated by Pearson’s correlation coefficient.ResultsIn patients, |G*| was significantly reduced in the frontal and mesencephalic regions (p < 0.05). Beyond that, reduced mesencephalic |G*| discriminated PSP from PD (p < 0.05). Neurodegeneration causes significant brain atrophy (p < 0.01) and is pronounced in PSP patients (p < 0.05 vs. PD). Reduced brain viscoelasticity is correlated with brain atrophy in PSP (r=0.64, p=0.002) and PD (r=0.65, p=0.005) patients but not in controls.ConclusionsMRE-measured viscoelasticity reflects local structural changes of brain tissue in PSP and in PD and provides a useful parameter to differentiate neurodegenerative movement disorders based on imaging examinations.Key points• 3D multifrequency MR-elastography reveals diffuse regional changes in brain viscoelasticity in neurodegenerative disorders.• Reduced mesencephalic viscoelasticity separates PD and PSP.• Reduced brain viscoelasticity and brain atrophy as independent hallmarks of neurodegeneration hypothesized.