Brain viscoelasticity alteration in chronic-progressive multiple sclerosis

Abstract

Introduction: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS) is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS.

Methods: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS.

Results: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001).

Conclusions: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

Figure 1. Scheme of cerebral multifrequency MRE.

a: The MRI scanner is combined with a device for acoustical head stimulations comprising: 1) a signal generator that produces a multifrequency signal composed from four harmonic frequencies of 25, 37.5, 50 and 62.5 Hz; 2) a loudspeaker for generating acoustic vibrations; 3) an extended piston that transfers the vibrations into the scanner and 4) a head cradle for stimulating head vibrations mainly along the head-feet direction. b: A single-shot echo planar imaging (EPI) sequence is sensitized to harmonic motions by a 60-Hz sinusoidal motion encoding gradient (MEG) of four cycles and directed through-plane. The image planes are positioned in transverse orientation through the brain (parallel to the “anterior and posterior commissure line (AC-PC)”) in a central slab of the brain. The resulting wave images display the motion component along the head-feet direction corresponding to the major vibration direction of the actuator. c: Image processing comprises Fourier decomposition of the superposed oscillations yielding four complex single-frequency wave images, corresponding to the experimentally applied vibration frequencies. Each of the wave images is separately inverted, resulting in four complex-valued shear modulus images, whose values are averaged within a region of interest comprising the parenchyma within the image slice (demarcated in the wave images by white lines).

Figure 2. Brain atrophy in MS patients.

Significantly reduced brain parenchymal volume (a) and brain parenchymal fraction (BPF) (b) in MS patients compared to matched healthy individuals (*** P<0.001). The boxplots depict the lower and upper quartiles as well as the 50^th percentile (median). Full data range is presented by the whiskers. sp – secondary progressive, pp – primary progressive, rr – relapsing remitting.

Figure 3. Reduction of brain parenchymal viscoelastic constants.

MS patients present with significantly reduced brain parenchymal elasticity μ (a, P<0.001), but also with a reduction in the powerlaw exponent α (b, P<0.001) in MS patients with progressive disease course. The boxplot depicts the lower and upper quartiles as well as the 50^th percentile (median). Full data range is presented by the whiskers. sp – secondary progressive, pp – primary progressive, rr – relapsing remitting; *data for rr-MS are taken from and reprocessed according to the methods reported in herein.

Figure 4. Viscoelastic constants for the detection of brain pathology.

Individual data of shear elasticity μ and powerlaw exponent α of brain tissue in healthy volunteers and MS patients. The areas under the receiver characteristics curve (AUROC) for separating healthy volunteers from MS patients are 0.896 and 0.936 for μ and α, respectively.