# Time-Domain Near-Infrared Spectroscopy in Subjects with Asymptomatic Cerebral Small Vessel Disease
###### Abstract  
Biomarkers of microcirculation dysfunction may help in the study of cerebral small vessel disease (CSVD). Time-Domain Near-Infrared spectroscopy (TD-NIRS), estimating the oxygenation of microcirculation of cerebral outer layers, might indirectly correlate with CSVD. We retrospectively evaluated TD-NIRS data from healthy subjects with age \(\geq\) 55 years; no history of brain disease; normal neurological examination; absence of stenosis > 50% of extra/intra-cranial arteries; incidental finding of asymptomatic CSVD at brain magnetic resonance imaging (MRI). According to Fazekas scale, subjects were classified by presence of white matter hyperintensities in periventricular region (pvWMHs), deep white matter region (dWMHs), or both (d+pvWMHs). We compared the concentration of hemoglobin species and tissue oxygen saturation (SO\({}_{2}\)) among these groups. The study included 20 subjects, median age 67.5 (IQR 61-78) years old (6 without WMHs, 5 with pvWMHs, 9 with d+pvWMHs). Subjects with d+pvWMHs had significantly lower S\({}_{\rm O}\)O compared to subjects without WMHs (\(p\) = 0.022) or with pvWMHs (\(p\) = 0.004). S\({}_{\rm O}\)O\({}_{2}\) < 56.7% indicated the presence of d+pvWMHs with 91% sensitivity and 67% specificity [AUC 91% (CI 95% 78-100%)]. In this preliminary study, cerebral TD-NIRS detected significantly lower S\({}_{\rm O}\)O\({}_{2}\) in subjects with radiological signs of asymptomatic CSVD. Further studies are needed to evaluate if S\({}_{\rm O}\)\({}_{2}\) might represent a marker of asymptomatic CSVD. microcirculation dysfunction in cerebral small vessel disease; asymptomatic cerebral small vessel disease; NIRS in cerebrovascular diseases; oxygen saturation in cerebral small vessel disease; novel applications of time-domain near-infrared spectroscopy; TD-NIRS; time-resolved near-infrared spectroscopy; neuroimaging of leukoarayiosis; Fazekas scale and white matter hyperintensities; NIRS in healthy subjects +
Footnote †: journal: Medical Imaging  
proteins and other plasma constituents into the perivascular tissues, which might increase interstitial fluid, stiffen arteriole and venule walls [1]. The effects of these phenomena impair cerebrovascular reactivity, vascular pulsatility, hemodynamic blood flow redistribution, leading to inefficient oxygen and nutrient transport, and to neurovascular dysfunction. Cerebral infarction may finally result from arteriolar occlusion and hemodynamic insufficiency phenomena. Asymptomatic CSVD, defined as neuroimaging evidence of CSVD prior to the development of any overt clinical symptoms, is common in adult healthy subjects regardless of associated vascular risk factors [4]. Usually, the clinical manifestation of the disease becomes evident with accumulation of brain lesions. Imaging markers of CSVD, including lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS) and cerebral microbleeds (CMBs) are commonly observed on brain MRI in healthy individuals. The reported prevalence of these lesions in elderly populations varies across different studies, ranging from 8% to 33% for lacunes [5], 3% to 34% for CMBs [6], and 39% to 96% for WMHs [7]. Fazekas scale, which classifies WMHs in periventricular and deep white regions, is one of the most used scoring systems to classify CSVD [8]. The typical lesions of CSVD are indeed located in the white matter of centrum semiovale, in periventricular regions and in deep structures, even though the functional alteration of microcirculation affects both cortical and white matter arterioles, capillaries and venules. The detection of meaningful biomarkers of asymptomatic CSVD is one among the unmet needs of CSVD. Advanced optical devices, such as time-domain near infrared spectroscopy (TD-NIRS), might provide useful information about oxygenation of cerebral microcirculation in the superficial layers in a non-invasive way, with limited costs and overcoming some limitations of previous NIRS systems, such as continuous-wave NIRS.