Association between BPF and OCT parameters in patients with RRMS.

<p>Patients (individual eyes) are labeled according to the history of optic neuritis (ON). Lines are derived from linear regression analyses with R² given in parentheses. Statistical significance level was calculated by Generalized Estimating Equation models controlling for the history of ON. A) Retinal nerve fiber layer thickness (RNFLT) vs. BPF (0.073, p = 0.019). B) Total macular volume (TMV) vs. BPF (0.113, p = 0.001).</p

Description of study cohort with demographic and disease parameters.

<p>RRMS = relapsing remitting Multiple sclerosis; (N)ON = (non) optic neuritis; SD = standard deviation, BPF = brain parenchymal fraction, RNFLT = retinal nerve fiber layer thickness, TMV = total macular volume.</p

Generalized Estimating Equations for the association of RNFLT with BPF as primary endpoint.

<p>Results from GEEs with RNFLT and age as independent variables and controlling for history of optic neuritis and BPF as dependent variable. The standardized Beta was calculated as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018132#s2" target="_blank">methods</a> section. RNFLT = retinal nerve fiber layer thickness, ON = history of optic neuritis, CI = confidence interval.</p

Correlation of RNFLT with BPF and ¹H-MRS parameters.

<p>a) Depicted is the average RNFLT, every symbol representing a single eye examined together with the corresponding BPF values. The symbols represent the patient's previous history of optic neuritis (open circles – no previous optic neuritis, grey squares - unilateral optic neuritis, black triangles – bilateral optic neuritis) A linear correlation function was calculated by a Generalised Linear Model to account for intra-individual inter-eye relationships (p = 0.001). b) Mean BPF was calculated for three groups that were defined based on their previous history of optic neuritis (white bar– no previous optic neuritis, grey bar - unilateral optic neuritis, black bar – bilateral optic neuritis). The (-) symbol indicates a trend, but a missing significant correlation of group differences as calculated by ANOVA (p = 0.055). Error bars represent 2× standard error of the mean (SEM). c) RNFLT averages are shown in relation to corresponding NAA concentrations in the visual cortex (VC). The symbols are coded as in a). The correlation is significant (p = 0.047). d) Mean visual cortex voxel (VC) NAA and the significance of group differences was calculated for optic neuritis groups as in b). The asterisk indicates statistically significant (p = 0.046) group differences. Error bars represent 2× standard error of the mean (SEM). e) RNFLT averages are shown in relation to corresponding NAA concentrations in normal-appearing white matter (NAWM). The symbols are coded as in a). No significant correlation was found (p = 0.531). f) Mean NAA in normal-appearing white matter (NAWM) and the significance of group differences was calculated for optic neuritis groups as in b) (p = 0.429). Error bars represent 2× standard error of the mean (SEM).</p

Statistical data for GEE and combined model GEE (NAWM = normal-appearing white matter, VC = visual cortex).

<p>Statistical data for GEE and combined model GEE (NAWM = normal-appearing white matter, VC = visual cortex).</p

Summary of demographic data, mean RNFLT, mean BPF, mean normal-appearing white matter (NAWM) NAA concentrations, mean visual cortex (VC) NAA concentrations.

<p>(NON/NON – no previous optic neuritis, NON/ON – previous unilateral optic neuritis, ON/ON - previous bilateral optic neuritis).</p

¹H-MRS voxel placement.

<p>Visual representation of typical voxel placement for MR spectroscopy. In each patient, NAA concentrations were measured in a visual cortex voxel (VC) and two normal-appearing white matter voxels (NAWM).</p