# Time-Domain Near-Infrared Spectroscopy in Subjects with Asymptomatic Cerebral Small Vessel Disease
## 3 Results  
The study cohort comprised 20 subjects [median age 67.5 (IQR 61-78) years old] of which 6 subjects had noWMHs, 5 subjects had pvWMHs, and 9 subjects had d+pvWMHs. There were no subjects belonging to dWMHs group since all subjects with dWMHs also had pvWMHs. Demographic features, vascular risk factors, clinical and laboratory parameters including arterial blood pressure, heart rate, SpO\({}_{2}\), mean peripheral blood hemoglobin concentration of the three groups are reported in Table 1.  
There was a significant difference of StO\({}_{2}\) values among groups (\(p=0.007\)) (Table 2). In pairwise comparisons, subjects with noWMHs had StO\({}_{2}\) values comparable to subjects with pvWMHs (\(p=0.53\)) while subjects with d+pvWMHs had significantly lower StO\({}_{2}\) compared to noWMHs (\(p=0.022\)) and to pvWMHs (\(p=0.004\)). We performed an explorative multiple linear regression analysis with increasing extension of WMHs (Fazekas groups) as dependent variable (0 = no WMHs, 1 = pvWMHs, 2 = d+pvWMHs). According to univariate analysis, age, arterial hypertension, smoking, SpO\({}_{2}\) and StO\({}_{2}\) were entered as independent variables (all independent variables entered into the equation at the same time as \"enter\" method). We calculated the power of the linear multiple regression analysis (fixed model, R\({}^{2}\) increase) according to the following characteristics: sample size = 20, alpha = 0.05, number of predictors = 5, alpha \(\backslash\) beta ratio = 1. The estimated power according to large, medium and low effect sizes \(f^{2}\) (respectively,  
Figure 1: Time-Domain Near-Infrared spectroscopy (TD-NIRS) measurement set-up. (**a**) TD-NIRS device; (**b**) head-of-bed inclination; (**c**) probed positions on the scalp and grand average of recovered concentrations of HbR, HbO, HbT and of StO\({}_{2}\) value. \(\hat{t}^{2}=0.35\), \(\hat{t}^{2}=0.15\), \(\hat{t}^{2}=0.02\)) were respectively 86%, 73%, 54%. Variance inflation factors below 1.5 excluded the presence of collinearity. Independence of residuals was confirmed by Durbin-Watson statistic. Homoscedasticity was evaluated by visual inspection of a plot of standardized residuals versus standardized predicted values. The normality of the distribution of residuals was assessed by visual inspection of a normal P-P plot. The regression model significantly predicted Fazekas groups F (5, 19) = 8.8, \(p=0.001\) and had a R\({}^{2}\) = 76%. According to the linear regression model, StO\({}_{2}\), age and arterial hypertension were significantly associated with increasing extension of WMHs (Table 3). In an explorative ROC analysis, grouping together noWMHs and pvWMHs subjects, a cut-off of cerebral StO\({}_{2}\) < 56.7% indicated the presence of d+pvWMHs with 91% sensitivity and 67% specificity [AUC 91% (CI 95% 78-100%)] (Figure 2). \begin{table}
\begin{tabular}{c c c c c} \hline \hline  & **noWMHs** & **pvWMHs** & **d+pvWMHs** & \\  & \(n\) = 6 & \(n\) = 5 & \(n\) = 9 & \(p\) \\ \hline Age (years) * & 59 (56–61) & 68 (67–78) & 70 (70–77) & 0.015 \\ Gender (M/F) & 83/17\% & 80/20\% & 44/56\% & 0.22 \\ Arterial hypertension & 17\% & 20\% & 67\% & 0.09 \\ Diabetes mellitus & 0\% & 40\% & 33\% & 0.23 \\ Smoking & 33\% & 0\% & 0\% & 0.07 \\ Hypercholesterolemia & 17\% & 20\% & 11\% & 0.9 \\ Atrial fibrillation & 0\% & 0\% & 22\% & 0.26 \\ Migraine & 0\% & 20\% & 11\% & 0.54 \\ MAP (mmHg) * & 95 (88–97) & 90 (87–90) & 90 (87–103) & 0.63 \\ Heart rate (beats/min) * & 64 (60–70) & 65(60–73) & 71 (65–82) & 0.60 \\ SpO\({}_{2}\) (\%) * & 99 (98–99) & 97 (96–97) & 98 (98–99) & 0.06 \\ Hb (g/dl) * & 13.9 (1.4) & 13.9 (0.5) & 13.2 (1.2) & 0.56 \\ \hline \hline \end{tabular}  
* Median (IQR); MAP: mean arterial blood pressure; SpO\({}_{2}\): peripheral pulse oximetry; Hb: blood hemoglobin concentration.  
\end{table} 
Table 1: Comparison of demographic and clinical characteristics according to Fazekas groups.