Applications of diffuse optical spectroscopy in exercise physiology and metabolic disease

While medical practitioners increasingly appreciate the importance of exercise and diet in management of metabolic disorders, there are still few clinical diagnostic tools to assess the effects of these "lifestyle" interventions. Near-infrared spectroscopy (NIRS) is uniquely suited to this purpose because it is non-invasive, non-harmful, and can be used in a variety of tissues. The purpose of these studies is to apply two techniques of NIRS: time-resolved NIRS (TR-NIRS), and frequency domain diffuse optical spectroscopic imaging (DOSI) to physiological studies in humans. The first set of studies describes the use of TR-NIRS to study incremental exercise in children and adolescents. TR-NIRS signals are use to quantify tissue-specific responses to increasing exercise intensity, as well as to determine correlation of thresholds with those occurring in ventilation data. Secondly, the effect of training is assessed by conducting cerebral TR-NIRS measurements before an 8 week training session. And finally, the paradigm of blood flow restriction exercise is investigated as a way of perturbing muscle and cerebral hemodynamics during resistance exercise. The second portion of these studies involves the application of DOSI to the study of subcutaneous adipose tissue (AT). The role of AT in the pathophysiology of metabolic disease is increasingly appreciated, but method to measure AT function are limited. We hypothesized that DOSI would be sensitive to changes in AT optical properties with calorie restriction, and conducted a pilot study along those lines. DOSI detected changes in both optical scattering and absorption that are consistent with known phenomena that occur in AT with weight loss, ie reduction in fat cell volume, increased O2 extraction, and increased hydration. These findings might constitute an optical signature of AT that correlates with improvement in overall metabolism. Taken together, these studies introduce novel contributions in the field of optical imaging in the context of obesity, metabolism and exercise

Effect of blood flow restriction on tissue oxygenation during knee extension.

PURPOSE: Time-resolved near-infrared spectroscopy was used to quantify tissue oxy- and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2) in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex during knee extension with and without blood flow restriction (BFR). METHODS: Six young healthy males performed three sets of knee extensions on a dynamometer (50% one-repetition maximum) separated by 90-s rest periods in three conditions: 1) until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff constriction around thigh (BFR)), 3) same number of repetitions from condition 2 without BFR (matched). Each condition was performed on a separate visit. RESULTS: BFR was associated with higher [HbR] at the oblique fibers of the vastus medialis muscle (rest 1: 57.8 (BFR) vs 35.0 μM (matched); P < 0.0001) and a significantly lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method, a spike in [HbR] was observed before the onset of HbR clearance during recovery, causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 μM (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR, with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of increase (BFR, 58 μM·min; matched, 89 μM·min; P = 0.004) during recovery. In the prefrontal cortex, BFR was associated with increased [HbR], diminished increase in [HbO2], and higher subjective exertion. CONCLUSIONS: These findings yield insight into possible physiological mechanisms of BFR and suggest a role of time-resolved near-infrared spectroscopy in monitoring and optimization of BFR exercise on an individual basis

Cerebral and Muscle Tissue Oxygenation During Incremental Cycling in Male Adolescents Measured by Time-Resolved Near-Infrared Spectroscopy.

Near-infrared spectroscopy has long been used to measure tissue-specific O2 dynamics in exercise, but most published data have used continuous wave devices incapable of quantifying absolute Hemoglobin (Hb) concentrations. We used time-resolved near-infrared spectroscopy to study exercising muscle (Vastus Lateralis, VL) and prefrontal cortex (PFC) Hb oxygenation in 11 young males (15.3 ± 2.1 yrs) performing incremental cycling until exhaustion (peak VO2 = 42.7 ± 6.1 ml/min/kg, mean peak power = 181 ± 38 W). Time-resolved near-infrared spectroscopy measurements of reduced scattering (μs´) and absorption (μa) at three wavelengths (759, 796, and 833 nm) were used to calculate concentrations of oxyHb ([HbO2]), deoxy Hb ([HbR]), total Hb ([THb]), and O2 saturation (stO2). In PFC, significant increases were observed in both [HbO2] and [HbR] during intense exercise. PFC stO2% remained stable until 80% of total exercise time, then dropped (-2.95%, p = .0064). In VL, stO2% decreased until peak time (-6.8%, p = .01). Segmented linear regression identified thresholds for PFC [HbO2], [HbR], VL [THb]. There was a strong correlation between timing of second ventilatory threshold and decline in PFC [HbO2] (r = .84). These findings show that time-resolved near-infrared spectroscopy can be used to study physiological threshold phenomena in children during maximal exercise, providing insight into tissue specific hemodynamics and metabolism

Cerebral and Muscle Tissue Oxygenation During Incremental Cycling in Male Adolescents Measured by Time-Resolved Near-Infrared Spectroscopy

Near-infrared spectroscopy has long been used to measure tissue-specific O2 dynamics in exercise, but most published data have used continuous wave devices incapable of quantifying absolute Hemoglobin (Hb) concentrations. We used time-resolved near-infrared spectroscopy to study exercising muscle (Vastus Lateralis, VL) and prefrontal cortex (PFC) Hb oxygenation in 11 young males (15.3 ± 2.1 yrs) performing incremental cycling until exhaustion (peak VO2 = 42.7 ± 6.1 ml/min/kg, mean peak power = 181 ± 38 W). Time-resolved near-infrared spectroscopy measurements of reduced scattering (μs´) and absorption (μa) at three wavelengths (759, 796, and 833 nm) were used to calculate concentrations of oxyHb ([HbO2]), deoxy Hb ([HbR]), total Hb ([THb]), and O2 saturation (stO2). In PFC, significant increases were observed in both [HbO2] and [HbR] during intense exercise. PFC stO2% remained stable until 80% of total exercise time, then dropped (-2.95%, p = .0064). In VL, stO2% decreased until peak time (-6.8%, p = .01). Segmented linear regression identified thresholds for PFC [HbO2], [HbR], VL [THb]. There was a strong correlation between timing of second ventilatory threshold and decline in PFC [HbO2] (r = .84). These findings show that time-resolved near-infrared spectroscopy can be used to study physiological threshold phenomena in children during maximal exercise, providing insight into tissue specific hemodynamics and metabolism

Effect of blood flow restriction on tissue oxygenation during knee extension.

PurposeTime-resolved near-infrared spectroscopy was used to quantify tissue oxy- and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2) in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex during knee extension with and without blood flow restriction (BFR).MethodsSix young healthy males performed three sets of knee extensions on a dynamometer (50% one-repetition maximum) separated by 90-s rest periods in three conditions: 1) until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff constriction around thigh (BFR)), 3) same number of repetitions from condition 2 without BFR (matched). Each condition was performed on a separate visit.ResultsBFR was associated with higher [HbR] at the oblique fibers of the vastus medialis muscle (rest 1: 57.8 (BFR) vs 35.0 μM (matched); P < 0.0001) and a significantly lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method, a spike in [HbR] was observed before the onset of HbR clearance during recovery, causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 μM (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR, with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of increase (BFR, 58 μM·min; matched, 89 μM·min; P = 0.004) during recovery. In the prefrontal cortex, BFR was associated with increased [HbR], diminished increase in [HbO2], and higher subjective exertion.ConclusionsThese findings yield insight into possible physiological mechanisms of BFR and suggest a role of time-resolved near-infrared spectroscopy in monitoring and optimization of BFR exercise on an individual basis

Characterizing tourniquet induced hemodynamics during total knee arthroplasty using diffuse optical spectroscopy.

Tourniquet use creates a reduced blood surgical field during total knee arthroplasty (TKA), however, prolonged ischemia may cause postoperative tourniquet complications. To understand the effects of tourniquet-induced ischemia, we performed a prospective observational study using quantitative broadband diffuse optical spectroscopy (DOS) to measure tissue hemodynamics and water and lipid concentrations before, during, and after tourniquet placement in subjects undergoing TKA. Data was collected for 6 months and, of the total subjects analyzed (n = 24), 22 were primary TKAs and 2 were revision TKA cases. We specifically investigated tourniquet-induced hemodynamics based upon subject-specific tissue composition and observed a significant relationship between the linear rate of deoxygenation after tourniquet inflation and water/lipid ratio (W/L, p < 0.0001) and baseline somatic tissue oxygen saturation, StO2 (p = 0.05). Subjects with a low W/L ratio exhibited a lower tissue metabolic rate of oxygen consumption, (tMRO2 ) (p = 0.008). Changes in deoxyhemoglobin [HbR] (p = 0.009) and lipid fraction (p = 0.001) were significantly different between high and low W/L subject groups during deoxygenation. No significant differences were observed for hemodynamics during reperfusion and total tourniquet time was neither significantly related to the hemodynamic hyperemic response (p = 0.73) nor the time to max StO2 after tourniquet release (p = 0.57). In conclusion, we demonstrate that DOS is capable of real-time monitoring of tissue hemodynamics distal to the tourniquet during TKA, and that tissue composition should be considered. DOS may help surgeons stratify hemodynamics based upon tissue composition and eventually aid the preoperative risk assessment of vascular occlusions from tourniquet use during TKA

Effect of blood flow restriction on tissue oxygenation during knee extension.

PurposeTime-resolved near-infrared spectroscopy was used to quantify tissue oxy- and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2) in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex during knee extension with and without blood flow restriction (BFR).MethodsSix young healthy males performed three sets of knee extensions on a dynamometer (50% one-repetition maximum) separated by 90-s rest periods in three conditions: 1) until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff constriction around thigh (BFR)), 3) same number of repetitions from condition 2 without BFR (matched). Each condition was performed on a separate visit.ResultsBFR was associated with higher [HbR] at the oblique fibers of the vastus medialis muscle (rest 1: 57.8 (BFR) vs 35.0 μM (matched); P < 0.0001) and a significantly lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method, a spike in [HbR] was observed before the onset of HbR clearance during recovery, causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 μM (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR, with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of increase (BFR, 58 μM·min; matched, 89 μM·min; P = 0.004) during recovery. In the prefrontal cortex, BFR was associated with increased [HbR], diminished increase in [HbO2], and higher subjective exertion.ConclusionsThese findings yield insight into possible physiological mechanisms of BFR and suggest a role of time-resolved near-infrared spectroscopy in monitoring and optimization of BFR exercise on an individual basis

Fasting Glucose Level Modulates Cell Surface Expression of CD11b and CD66b in Granulocytes and Monocytes of Patients with Type II Diabetes

Cardiovascular complications are the leading cause of mortality in type II diabetes (T2DM), in which onset and progression of atherosclerosis is linked to chronic inflammation. Activation status of innate immune cells (granulocytes Gc, monocytes Mc), as reflected by increased CD11b, CD66b and other surface markers, increases their endothelial and cytokines/chemokines release. While this inflammatory activation appears inversely related to poor glycemic control, the effect of acute spontaneous hyperglycemia on innate immune cell activation remains unclear. Expression of key markers (CD11b, CD14, CD16, CD62L, and CD66b) was therefore determined by flow cytometry on whole blood of healthy subjects and patients with T2DM with spontaneous, fasting eu- or hyper-glycemia both at baseline and after 30, 90, and 240 min. of room temperature incubation. Hyperglycemic patients with T2DM had significantly higher Gc and Mc CD11b and Gc CD66b surface mean fluorescence intensity (MFI) as compared to euglycemic patients with T2DM whose values were similar to healthy controls. CD16 expression in CD14+CD16+ Mc was elevated in all patients with T2DM, regardless of glycemic levels. Our data suggest that while the presence of diabetes per se may have a pro-inflammatory effect, hyperglycemia seems further acutely exacerbate innate cell inflammatory status, and their consequent endothelial adhesion and vascular damage potential

Exercise and Repeated Testing Improves Accuracy of Laser Doppler Assessment of Microvascular Function Following Shortened (1-minute) Blood Flow Occlusion.

ObjectivesTo determine whether stability/accuracy of post-occlusive LDF following shortened, one-minute blood flow occlusion, increases in the post-exercise state or by averaging multiple measurements.MethodsSix healthy adults (3F) underwent LDF eight times at rest and following exercise, assessing post-occlusive (one-minute occlusion) reactive hyperemia in the cutaneous microcirculation of the forefinger. Measured variables included: pre- and post-occlusion steady-state perfusion (Plat1, Plat2), maximum post-occlusive perfusion (Max), PkT, and the ratio Max/Plat1.ResultsStability/accuracy of all variables improved performing measurements after exercise (p < 0.05 Plat 1, Plat 2, Max and Max/Plat1). PkT and Max/Plat 1 displayed the greatest accuracy at rest (26.6 ± 5.1% and 26.6 ± 4.4% average difference, %Diff, of single measurements from individual "true" means, respectively); for these variables, %Diff improved to 19.5 ± 5.3 and 17.6 ± 2.1, respectively, following exercise. Overall, averaging multiple measurements performed at rest also improved stability/accuracy in all variables. This improvement was comparable to that obtained with a single measurement following exercise.ConclusionsA standardized exercise stimulus prior to testing significantly improves stability/accuracy of LDF following shortened, one-minute blood flow occlusion. Our results suggest the possibilities of broader applications of exercise to optimize measurements from a variety of skin perfusion methodologies