A Bayesian Marked Hierarchical Spatial Point Process Model with Covariates for Lesion Data

Poster submitted to the 2016 Organization for Human Brain Mapping (OHBM) in Geneva, 26-30 June

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

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

Viscoelastic constants for the detection of brain pathology.

<p>Individual data of shear elasticity <i>μ</i> and powerlaw exponent <i>α</i> 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 <i>μ</i> and <i>α</i>, respectively.</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

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

Enlargement of Cerebral Ventricles as an Early Indicator of Encephalomyelitis

<div><p>Inflammatory disorders of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis involve an invasion of immune cells that ultimately leads to white matter demyelination, neurodegeneration and development of neurological symptoms. A clinical diagnosis is often made when neurodegenerative processes are already ongoing. In an attempt to seek early indicators of disease, we studied the temporal and spatial distribution of brain modifications in experimental autoimmune encephalomyelitis (EAE). In a thorough magnetic resonance imaging study performed with EAE mice, we observed significant enlargement of the ventricles prior to disease clinical manifestation and an increase in free water content within the cerebrospinal fluid as demonstrated by changes in T₂ relaxation times. The increase in ventricle size was seen in the lateral, third and fourth ventricles. In some EAE mice the ventricle size started returning to normal values during disease remission. In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset. Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.</p> </div

T₁ values for gray matter and white matter in healthy volunteers at 1.5T, 3T, and 7T derived from IR-SE reference measurement, uncorrected 2D VFA, and corrected 2D VFA.

<p>T₁ values for gray matter and white matter in healthy volunteers at 1.5T, 3T, and 7T derived from IR-SE reference measurement, uncorrected 2D VFA, and corrected 2D VFA.</p

Changes in volume for the single ventricular compartments.

<p>Shown is a graphical representation of the temporal changes in volume for both lateral (A), left lateral (B), right lateral (C), third (D) and fourth (E) ventricles for all EAE (n=20) and control (n=6) mice. All points represent a ratio of the daily ventricle volume to the ventricle volume prior to immunization (baseline d-15) and are synchronized to the day of clinical disease onset.</p

Pre-symptomatic changes in ventricle size in an EAE mouse model.

<p>(A) T₂-weighted horizontal views of the mouse brain show the evolution of changes in ventricle size of a representative mouse from baseline (pre EAE induction) 15 days prior (d-15) to disease manifestation up till 4 days after disease manifestation (d +4). (B) Shown are 20 mice (1–20) exhibiting increase in ventricle volume prior to or concurrent to disease onset. For each animal, gray bars represent the first occurrence of ventricle enlargement and ensuing time points following EAE induction and black vertical lines indicate the symptom onset post immunization. The animals were sorted according to the time difference between first changes in ventricle size (light gray bars) and onset of clinical symptoms post immunization (black vertical lines). Mouse 1 exhibited ventricle enlargement 5 days prior to clinical symptoms, Mouse 17 – Mouse 19 exhibited ventricle enlargement on the same day as clinical symptoms and Mouse 20 showed no ventricle enlargement.</p