Functional-Optical Coherence Tomography: A Non-invasive Approach to Assess the Sympathetic Nervous System and Intrinsic Vascular Regulation

Abstract

Sympathetic nervous system dysregulation and vascular impairment in neuronal tissue beds are hallmarks of prominent cardiorespiratory diseases. However, an accurate and convenient method of assessing SNA and local vascular regulation is lacking, hindering routine clinical and research assessments. To address this, we investigated whether spectral domain optical coherence tomography (OCT), that allows investigation of retina and choroid vascular responsiveness, reflects sympathetic activity in order to develop a quick, easy and non-invasive sympathetic index. Here, we compare choroid and retina vascular perfusion density (VPD) acquired with OCT and heart rate variability (HRV) to microneurography. We recruited 6 healthy males (26 ± 3 years) and 5 healthy females (23 ± 1 year) and instrumented them for respiratory parameters, ECG, blood pressure and muscle sympathetic nerve microneurography. Choroid VPD decreases with the cold pressor test, inhaled hypoxia and breath-hold, and increases with hyperoxia and hyperpnea suggesting that sympathetic activity dominates choroid responses. In contrast, retina VPD was unaffected by the cold pressor test, increased with hypoxia and breath hold and decreases with hyperoxia and hyperpnea, suggesting metabolic vascular regulation dominates the retina. With regards to integrated muscle sympathetic nerve activity, HRV had low predictive power whereas choroid VPD was strongly (inversely) correlated with integrated muscle sympathetic nerve activity (R = -0.76; p < 0.0001). These data suggest that Functional-OCT may provide a novel approach to assess sympathetic activity and intrinsic vascular responsiveness (i.e., autoregulation). Given that sympathetic nervous system activity is the main determinant of autonomic function, sympathetic excitation is associated with severe cardiovascular/cardiorespiratory diseases and autoregulation is critical for brain health, we suggest that the use of our new Functional-OCT technique will be of broad interest to clinicians and researchers.

Keywords: autoregulation; choroid; microvascular; sympathetic nervous system; vascular.

FIGURE 1

Ophthalmic coherence tomography images demonstrating retina and choroid vascular perfusion and accompanying sympathetic nerve activity from one participant. Raw and processed images from a single participant of the retina (left two columns) and choroid (center two columns) during baseline and various cardiorespiratory challenges. Vascular perfusion is false colored in the raw images; blue and red represents high and low vascular perfusion, respectively. Retina and choroid VPD is demarcated by black pixels in the processed black and white images. Sympathetic activity was recorded from the peroneal nerve using microneurography and is rectified and integrated (right column). When sympathetic activity is low, perfusion in the choroid is high (A); when sympathetic activity is high, perfusion in the choroid is low (B). Note that the retina VPD remains relatively constant in comparison to the choroid.

FIGURE 2

The effect of sympatho-modulation on ophthalmic, cardiorespiratory and sympathetic parameters. Retina thickness (A), retina vascular perfusion density (Retina VPD, B), choroid vascular perfusion density (Choroid VPD, C), heart rate (HR, D), systolic blood pressure (SBP, E), diastolic blood pressure (DBP, F), mean arterial pressure (MAP, G), muscle sympathetic nervous activity (MSNA, H), minute ventilation (VE, I), end-tidal oxygen content (ETO₂, J), end-tidal carbon dioxide content (ETCO₂, K) in response to hyperoxia (green), hypoxia (blue), hyperpnea (magenta), hypercapnia (gray), breath hold (cyan) or cold pressor test (red). All data are presented as a percentage change from baseline. Absolute data were analyzed with Friedman’s non-parametric repeated measures ANOVA where (^∗) denotes a significant difference from baseline measures as assessed with Student Newman Keuls post hoc test; p-values are indicated within each bar.

FIGURE 3

Vascular perfusion density relationships with sympathetic nervous activity and mean arterial pressure for individual and mean data. The relationship of choroid vascular perfusion density (Choroid VPD) to muscle sympathetic nervous activity (MSNA) for individual (A) and mean data (B) in response to sympathetic provocations. The relationship of Choroid VPD to mean arterial pressure (MAP) for individual (C) and mean data (D) in response to sympathetic provocations. The relationship of retina vascular perfusion density (Retina VPD) to muscle sympathetic nervous activity (MSNA) for individual (E) and mean data (F) in response to sympathetic provocations. The relationship of retina VPD to mean arterial pressure (MAP) for individual (G) and mean data (H) in response to sympathetic provocations. All data are expressed as a percentage change from the initial baseline condition in response to hyperoxia (green), hypoxia (blue), hyperpnea (magenta), hypercapnia (gray), breath hold (cyan), or cold pressor test (red). Pearson R correlation coefficient with accompanying p-values are indicated within each panel. For relationships involving the retina, values in red text are inclusive of cold pressor test, values in solid text exclude cold pressor test.

FIGURE 4

Bland-Altman analysis of choroid VPD versus MSNA. The agreement between absolute choroid vascular perfusion density (Choroid VPD) and absolute muscle sympathetic nerve activity (MSNA, A), and percentage change of choroid VPD and percentage change of MSNA (B). Bland Altman analyses are expressed as the ratio of the two measures versus the average of the two measures. Dotted lines represent the lower and upper standard deviation. Absolute choroid VPD and MSNA Bias = 0.27, SD = 0.16; Percentage change choroid VPD and MSNA Bias = −4.30, SD = 24.48. Hyperoxia (green), hypoxia (blue), hyperpnea (magenta), hypercapnia (gray), breath hold (cyan), cold pressor test (red), baseline (gray).

FIGURE 5

Vascular regulatory mechanisms of autoregulation and sympathetic regulation are revealed by the retina and choroid. The relationships of choroid vascular perfusion density (Choroid VPD, A), retina vascular perfusion density (Retina VPD, B) to muscle sympathetic nervous activity (MSNA) in response to hypoxia (green) and hyperoxia (blue). The relationships of choroid VPD to retina VPD (C). Each data point represents each participant’s response to hyperoxia (green) and hypoxia (blue) as a percentage change from baseline. Pearson R correlation coefficient with accompanying p-values are indicated within each panel.