## 4 Discussion  
The main objective of the current investigation was to assess the ability of NIR-derived parameters to serve as a surrogate measure to a well-accepted approach of microvascular blood flow, strain-gauge plethysmography [42]. This was tested by performing a widely used, standardized protocol of VOP while simultaneously recording NIRS from a device fixed just distal to the strain-gauge (Figure 1). The major findings from our study included that (1) peak FBF (i.e., measure of RH) was poorly associated with all of the simultaneously collected NIRS variables (O\({}_{2}\)Hb, HHb, tHb, and HbDiff) and (2) there was suitable agreement for the men and women among the four consecutive resting values for each outcome variable (FBF, O\({}_{2}\)Hb, HHb, tHb, and HbDiff). These findings may help inform future microvascular-focused research studies as reported responses and measures of RH likely vary depending on the technique utilized (i.e., NIRS vs. strain-gauge plethysmography). Thus, the predictive power of RH for future onset and severity of CVD [2; 43] will likely need to be evaluated separately for each technique. Below, these findings are discussed in the context of previous, relevant findings. Strain-gauge and NIRS association. We hypothesized that the NIRS-derived variables (O\({}_{2}\)Hb, HHb, tHb, and HbDiff) would match the slopes of FBF pre- and post-transient ischemia, yet the results of the current study did not support this. Our findings were, however, similar to those of [PERSON] et al. [3], who also reported poor associations between FBF and NIRS-derived measures of resting tissue saturation index, O\({}_{2}\)Hb, and HHb values. These investigators mainly attributed the mismatch between NIRS and strain-gauge measures to the non-invasive approach of quantifying the rate of change (i.e., slope) in each parameter as opposed to move invasive procedures directly applying the Fick principle. In fact, earlier work [13; 44; 45] all reported a nearly perfect match between strain-gauge plethysmography and NIRS when utilizing the more invasive procedures. As previously noted, here, we only assessed the rate of change (i.e., slope values) in FBF and NIRS parameters in response to venous occlusion pre- and post-ischem, and no invasive measures were included. In addition, our findings did not agree with those of [PERSON] et al. [5], who reported a strong correlation for NIRS and strain-gauge measures, however, only after the use of a unique correction factor. Our findings also did not agree with the report of [PERSON] et al. [46], who showed a strong correlation between values captured from NIRS and the strain-gauge, yet there was disagreement during faster flow rates (e.g., RH), with NIRS consistently yielding underestimates of values. Furthermore, the slope values of the NIRS parameters in the current study were atypical analytical outcomes, such that generally a vascular occlusion test (absent of intermittent venous occlusion phases) is used to generate NIRS-based outcome measures (e.g., maximum tissue saturation). Despite the differences in methodological approaches, here, we were still able to suggest additional explanations to those previously presented by [PERSON] et al. [3]. Based on the present results, it was proposed that various reperfusion kinetics along the oxygen cascade contributed to the lack of association between FBF and NIRS parameters. As seen in Table 5, there were generally greater (i.e., faster) slopes for FBF compared to the NIRS measures, which indicated that the forearm increased in volume (due to venous pooling) faster than the forearm muscle group re-saturated. It is well-established that diffusive oxygen transport (capillary to myocyte) is a limiting factor in the genesis of aerobically derived cellular energy [47]. This diffusion capacity is affected by numerous factors, including capillary characteristics (e.g., density), red blood cell abundance and transit time, surface area, and solubility of oxygen [48; 49; 50].