Regional variation in the shear modulus of in vivo brain.

<p>All differences between the regions are statistically significant (p<0.001). The boxplot depicts the lower and upper quartiles as well as the median. Full data range (without outliers) is presented by whiskers. Crosses depict outliers.</p

Decrease in total brain volume and WM volume with age represented by linear regression of MRI volume data.

<p>Decrease in total brain volume and WM volume with age represented by linear regression of MRI volume data.</p

Regional variation in the parameter <i>α</i> representing the slope of the modulus dispersion and according to the springpot model.

<p>As <i>α</i> is sensitive to the microstructure geometry of biological tissue it is named ‘geometry’ parameter. Similar to <i>µ</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023451#pone-0023451-g003" target="_blank">Figure 3</a>), all regional differences are statistically significant (p<0.001).</p

Brain shear elasticity modulus averaged over the entire parenchyma visible in four image slices of all volunteers.

<p>Linear and quadratic regression is shown to indicate the order of softening of brain tissue with years of age.</p

Four image slices from T1-weighted volume MRI data compliant with MRE slice positions (upper row).

<p>Color-coded MRE wave data of 50 Hz vibrations. Blue colors scale vibrations towards the reader, while red to yellow colors scale motion beneath the image plane. The maximum tissue deflection is approximately 80<i> µ</i>m (mid row). Real-part modulus images corresponding to 50 Hz vibration frequency with specific regions of interest (ROIs) investigated in this study. Green lines: <i>ROI</i>_full, blue lines: <i>ROI</i>_inner, red lines: <i>ROI</i>_frontal, magenta lines: <i>ROI</i>_posterior, outer green lines excluding ventricles: <i>ROI</i>_full (bottom line).</p

Description of volume data and viscoelasticity parameters.

<p>The standard deviations (SD) are given in brackets.</p>a<p>dm³,</p>b<p>kPa.</p

Reduction of brain parenchymal viscoelastic constants.

<p>MS patients present with significantly reduced brain parenchymal elasticity <i>μ</i> (<b>a</b>, P<0.001), but also with a reduction in the powerlaw exponent <i>α</i> (<b>b</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 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029888#pone.0029888-Wuerfel1" target="_blank">[14]</a> and reprocessed according to the methods reported in herein.</p

Scheme of cerebral multifrequency MRE.

<p><b>a:</b> 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>b:</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. <b>c:</b> 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).</p

Demographical data, clinical characteristics, brain volumes, brain parenchymal fraction (BPF) and viscoelastic constants <i>μ</i> and <i>α</i> according to the springpot model.

<p>MS – multiple sclerosis; sp – secondary progressive; pp – primary progressive; rr – relapsing remitting; EDSS – expanded disability status scale; n.a. – not applicable; standard deviations are given in brackets;</p><p>*data taken from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029888#pone.0029888-Wuerfel1" target="_blank">[14]</a> and processed corresponding to the data of progressive MS.</p

Brain atrophy in MS patients.

<p>Significantly reduced brain parenchymal volume (<b>a</b>) and brain parenchymal fraction (BPF) (<b>b</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.</p