Gwen Lech

Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies

We have employed near-infrared optical methods to measure noninvasively the dynamics of muscle blood flow and oxygen saturation (StO2) during cuff occlusion and plantar flexion exercise. Relative muscle oxygen consumption (rVO2) was also computed from these data. Diffuse correlation spectroscopy provides information about blood flow, and diffuse reflectance spectroscopy provides information about blood oxygenation. Ten healthy subjects and one patient with peripheral arterial disease (PAD) were studied during 3-min arterial cuff occlusion of arm and leg, and during 1-min plantar flexion exercise. Signals from different layers (cutaneous tissues and muscles) during cuff occlusion were differentiated, revealing strong hemodynamic responses from muscle layers. During exercise in healthy legs, the observed approximately 4.7 fold increase in relative blood flow (rBF) was significantly lower than the corresponding increase in rVO2 (approximately 7 fold). The magnitudes of rBF and rVO2 during exercise in the PAD patient were approximately 1/2 of the healthy controls, and the StO2 recovery time was twice that of the controls. The hybrid instrument improves upon current technologies for measuring muscle responses by simultaneously measuring rBF and StO2. The instrument thus provides a method for evaluation of microcirculation and muscle metabolism in patients with vascular diseases.

Noninvasive, low-noise, fast imaging of blood volume and deoxygenation changes in muscles using light-emitting diode continuous-wave imager

This article focuses on optimizing the signal to noise ratio (SNR) of a three-wavelength light-emitting diode (LED) near-infrared continuous-wave (cw) imager and its application to in vivo muscle metabolism measurement. The shot-noise limited SNR is derived and calculated to be 2×104 for the physiological blood concentrations of muscle. Aiming at shot-noise limited SNR performance and fast imaging, we utilize sample and hold circuits to reduce high-frequency noise. These circuits have also been designed to be parallel integrating, through which SNR of 2×103 and 2 Hz imaging acquisition rate have been achieved when the probe is placed on a muscle model. The noise corresponds to 2×10−4 optical density error, which suggests an in vitro resolution of 15. 4 nM blood volume and 46.8 nM deoxygenation changes. A 48 dB digital gain control circuit with 256 steps is employed to enlarge the dynamic range of the imager. We utilize cuff ischemia as a living model demonstration and its results are reported. The instrum...

Near infrared muscle spectroscopy in patients with Friedreich's ataxia

Friedreichs ataxia is a progressive neurodegenerative disorder of the afferent cerebellar pathways associated with mitochondrial dysfunction at the cellular level. We have used noninvasive continuous near infrared muscle spectroscopy (NIRS) to investigate the delivery and utilization of oxygen in response to exercise in this disorder. Patients performed an incremental treadmill walking protocol in which levels of muscle deoxygenation or oxygenation were continuously measured in the medial calf muscle. The kinetics of recovery from exercise‐induced deoxygenation, called the half‐time of recovery (t1/2) were determined. The t1/2 was prolonged in patients with Friedreichs ataxia compared with controls, and the degree of prolongation correlated with the length of the shorter GAA repeat, a genetic measure that correlates with the age of onset of disease. The t1/2 also correlated inversely with patient age and with the maximum treadmill speed attained. Several patients also displayed features consistent with inadequate oxygen utilization by muscle. These results suggest that NIRS may be an effective tool for monitoring the biochemical and functional features of Friedreichs ataxia in parallel.

Impaired Exercise-Induced Blood Volume in Type 2 Diabetes With or Without Peripheral Arterial Disease Measured by Continuous-Wave Near-Infrared Spectroscopy

OBJECTIVE—Diabetes is a significant risk factor for peripheral arterial disease (PAD) and is associated with accelerated atherosclerosis and limb loss. However, the pathophysiology involved in PAD is unclear. This study was conducted to evaluate the hemodynamic response to exercise of patients with and without diabetes and PAD. RESEARCH DESIGN AND METHODS—The hemodynamic response in calf muscles of patients with diabetes, PAD, or both was determined using near-infrared spectroscopy (NIRS). Patients performed both a plantar-flexion and treadmill-walking exercise regimen. RESULTS—Skeletal muscle capillary blood volume expansion during exercise, as measured by NIRS, was significantly impaired in the lower extremities of diabetic patients with a normal ankle-brachial index. The relative deoxygenation and oxygenation recovery times measured by NIRS correlates significantly with the presence of PAD. CONCLUSIONS—Patients with diabetes have reduced capillary volume expansion even without PAD. This is likely due to impaired vasodilation secondary to endothelial dysfunction. Further studies are needed to determine whether pharmaceutical intervention improves the blood volume expansion in the diabetic state.

Discrepancy between cardiorespiratory system and skeletal muscle in elite cyclists after hypoxic training

BackgroundThe purpose of this study was to determine the effects of hypoxic training on the cardiorespiratory system and skeletal muscle among well-trained endurance athletes in a randomized cross-over design.MethodsEight junior national level competitive cyclists were separated into two groups; Group A trained under normoxic condition (21% O2) for 2 hours/day, 3 days/week for 3 weeks while Group B used the same training protocol under hypoxic condition (15% O2). After 3 weeks of each initial training condition, five weeks of self-training under usual field conditions intervened before the training condition was switched from NT to HT in Group A, from HT to NT in Group B. The subjects were tested at sea level before and after each training period. O2 uptake (O2), blood samples, and muscle deoxygenation were measured during bicycle exercise test.Results and DiscussionNo changes in maximal workload, arterial O2 content, O2 at lactate threshold and O2max were observed before or after each training period. In contrast, deoxygenation change during submaximal exercise in the vastus lateralis was significantly higher at HT than NT (p < 0.01). In addition, half time of oxygenation recovery was significantly faster after HT (13.2 ± 2.6 sec) than NT (18.8 ± 2.7 sec) (p < 0.001).ConclusionsThree weeks of HT may not give an additional performance benefit at sea level for elite competitive cyclists, even though HT may induce some physiological adaptations on muscle tissue level.

Diffuse optical characterization of an exercising patient group with peripheral artery disease

Peripheral artery disease (PAD) is a common condition with high morbidity. While measurement of tissue oxygen saturation (S(t)O(2)) has been demonstrated, this is the first study to assess both S(t)O(2) and relative blood flow (rBF) in the extremities of PAD patients. Diffuse optics is employed to measure hemodynamic response to treadmill and pedal exercises in 31 healthy controls and 26 patients. For S(t)O(2), mild and moderate/severe PAD groups show pronounced differences compared with controls. Pre-exercise mean S(t)O(2) is lower in PAD groups by 9.3% to 10.6% compared with means of 63.5% to 66.2% in controls. For pedal, relative rate of return of S(t)O(2) to baseline is more rapid in controls (p < 0.05). Patterns of rBF also differ among groups. After both exercises, rBF tend to occur at depressed levels among severe PAD patients compared with healthy (p < 0.05); post-treadmill, rBF tend to occur at elevated levels among healthy compared with severe PAD patients (p < 0.05). Additionally, relative rate of return to baseline S(t)O(2) is more rapid among subjects with reduced levels of depression in rBF (p = 0.041), even after adjustment for ankle brachial index. This suggests a physiologic connection between rBF and oxygenation that can be measured using diffuse optics, and potentially employed as an evaluative tool in further studies.

USING FUNCTIONAL NEAR-INFRARED SPECTROSCOPY TO MEASURE COGNITIVE FUNCTION: WHEN WILL IT BECOME AN ACCEPTED CLINICAL TOOL FOR COGNITIVE AGING AND PRODROMAL DEMENTIA SCREENING?

This article presents a historical perspective of foundational studies utilizing near-infrared spectroscopy (NIRS) to measure the hemodynamics, oxygenation, and activation of the human brain cortex during cognitive tasks, called functional NIRS (fNIRS). It discusses studies representative of the diagnostic power and potential that fNIRS has shown for providing increased understanding of cognitive changes with aging and dementia. It concludes by discussing challenges that continue to confront the implementation of NIRS and fNIRS in clinical and translational research, in particular, the challenges to measure cognitive function and impairment in aged, chronically ill, and fragile subjects with or without dementia. It is written specifically in memoriam, honoring Britton Chance, therefore papers authored by him and his collaborative research family are weighted to illustrate the significant foundation and legacy he has left to this world.

Quantification of muscle oxygenation and flow of healthy volunteers during cuff occlusion of arm and leg flexor muscles and plantar flexion exercise

A hybrid instrument combining near infrared and diffuse correlation spectroscopies was used to measure muscle oxygenation and blood flow dynamics during cuff occlusion and ischemia. Measurements were done on six healthy subjects on their arm and leg flexor muscles. Hemodynamic response was characterized for blood oxygen saturation, total hemoglobin concenration and relative blood flow speed. The characterization allowed us to define the normal response range as well as showing the feasibility of using a hybrid instrument for dynamic measurements.

Non-invasive measurements of deep tissue hemodynamics in human skeletal muscle

Two near-infrared diffuse spectroscopies were used to simultaneously measure the blood flow and oxygenation in human skeletal muscles. The hemodynamics of nine healthy-volunteers and one PVD-patient during arterial cuff-occlusion and plantar-flexion exercise were characterized.

Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a patient with peripheral vascular disease (PVD) were found.