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Significance: There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases. Aim: To develop a wearable dual-wavelength diffuse speckle contrast flow oximetry (DSCFO) for simultaneous measurements of blood flow and oxygenation variations in deep tissues. Approach: A wearable fiber-free DSCFO probe was fabricated using 3D printing to confine two small near-infrared laser diodes and a tiny CMOS camera in positions for DSCFO measurements. The spatial diffuse speckle contrast and light intensity measurements at the two different wavelengths enable quantification of tissue blood flow and oxygenation, respectively. The DSCFO was first calibrated using tissue phantoms and then tested in adult forearms during artery cuff occlusion. Results: Phantom tests determined the largest effective source–detector distance (15 mm) and optimal camera exposure time (10 ms) and verified the accuracy of DSCFO in measuring absorption coefficient variations. The DSCFO detected substantial changes in forearm blood flow and oxygenation resulting from the artery occlusion, which meet physiological expectations and are consistent with previous study results. Conclusions: The wearable DSCFO may be used for continuous and simultaneous monitoring of blood flow and oxygenation variations in freely behaving subjects.

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultrasmall low-power CMOS camera as a two-dimensional detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements ( $\text{R}^{2}\geq \,{\text{0.80}}$ , $\text{p} ). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source–detector configuration allows for varied probing depths up to ${\sim\text{8 mm}}$ , which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

Introduction: Tissue injuries are often associated with abnormal blood flow (BF). The ability to assess BF distributions in injured tissues enables objective evaluation of interventions and holds the potential to improve the acute management of these injuries on battlefield. Materials and Methods: We have developed a novel speckle contrast diffuse correlation tomography (scDCT) system for noncontact 3D imaging of tissue BF distributions. In scDCT, a galvo mirror was used to remotely project near-infrared point light to different source positions and an electron multiplying charge-coupled-device was used to detect boundary diffuse speckle contrasts. The normalized boundary data were then inserted into a modified Near-Infrared Fluorescence and Spectral Tomography program for 3D reconstructions of BF distributions. This article reports the first application of scDCT for noncontact 3D imaging of BF distributions in burn wounds. Results: Significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues. Conclusions: The unique noncontact 3D imaging capability makes the scDCT applicable for intraoperative assessment of burns/wounds, without risk of infection and without interfering with sterility of the surgical field. The portable scDCT device holds the potential to be used by surgeons in combat surgical hospitals to improve the acute management of battlefield burn injuries.

OBJECTIVE Blood flow is one such available observable promoting a wealth of physiological insight both individually and in combination with other metrics. APPROACH Near-infrared diffuse correlation spectroscopy (DCS) and, to a lesser extent, diffuse correlation tomography (DCT), have increasingly received interest over the past decade as noninvasive methods for tissue blood flow measurements and imaging. DCS/DCT offers several attractive features for tissue blood flow measurements/imaging such as noninvasiveness, portability, high temporal resolution, and relatively large penetration depth (up to several centimeters). MAIN RESULTS This review first introduces the basic principle and instrumentation of DCS/DCT, followed by presenting clinical application examples of DCS/DCT for the diagnosis and therapeutic monitoring of diseases in a variety of organs/tissues including brain, skeletal muscle, and tumor. SIGNIFICANCE Clinical study results demonstrate technical versatility of DCS/DCT in providing important information for disease diagnosis and intervention monitoring.

Extremely preterm infants’ hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.

Objective To identify muscle physiologic properties that may contribute to postexertional fatigue and malaise in women with fibromyalgia (FM). Methods Healthy postmenopausal women with (n = 11) and without (n = 11) FM, ages 51–70 years, participated in this study. Physical characteristics and responses to self-reported questionnaires were evaluated. Strength loss and tissue oxygenation in response to a fatiguing exercise protocol were used to quantify fatigability and the local muscle hemodynamic profile. Muscle biopsies were performed to assess between-group differences in baseline muscle properties using histochemical, immunohistochemical, and electron microscopic analyses. Results There was no significant difference between healthy controls and FM patients in muscle fatigue in response to exercise. However, self-reported fatigue and pain were correlated with prolonged loss of strength following 12 minutes of recovery in patients with FM. Although there was no difference in percent succinate dehydrogenase (SDH)–positive (type I) and SDH-negative (type II) fibers or in mean fiber cross-sectional area between groups, FM patients exhibited greater variability in fiber size and altered fiber size distribution. In healthy controls only, fatigue resistance was strongly correlated with the size of SDH-positive fibers and hemoglobin oxygenation. In contrast, FM patients with the highest percentage of SDH-positive fibers recovered strength most effectively, and this was correlated with capillary density. However, overall, capillary density was lower in the FM group. Conclusion Peripheral mechanisms, i.e., altered muscle fiber size distribution and decreased capillary density, may contribute to postexertional fatigue in FM. Understanding of these defects in fibromyalgic muscle may provide valuable insight with regard to treatment.

Spontaneous low frequency oscillations (LFOs) around 0.1 Hz have been observed in mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV). Previous studies have shown that cerebral autoregulation in major arteries can be assessed by quantification of the phase shift between LFOs of MAP and CBFV. However, many cerebral diseases are associated with abnormal microvasculature and tissue dysfunction in brain, and quantification of these abnormalities requires direct measurement of cerebral tissue hemodynamics. This pilot study used a novel hybrid near-infrared diffuse optical instrument to noninvasively and simultaneously detect LFOs of cerebral blood flow (CBF) and cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: [HbO(2)]/[Hb]/THC) in human prefrontal cortex. Using the hybrid instrument and a finger plethysmograph, the dynamic changes of CBF, [HbO(2)], [Hb], THC and MAP were concurrently measured in 15 healthy subjects at rest, during 70° head-up-tilting (HUT) and during enforced breathing at 0.1 Hz. The LFOs were extracted from the measured variables using power spectral analysis, and the phase shifts and coherences of LFOs between MAP and each of the measured hemodynamic variables were calculated from the corresponding transfer functions. Levels of coherence (>0.4) were used to judge the success of LFO measurements. We found that CBF, [HbO(2)] and THC were reliable hemodynamic parameters in detecting LFOs and HUT was the most robust and stable protocol for quantifying phase shifts of hemodynamic LFOs. Comparing with other relevant studies, similar success rates for detecting cerebral LFOs have been achieved in our study. The phase shifts of LFOs in CBF were also close to those in CBFV reported by other groups, although the results in cerebral oxygenation measurements during enforced breathing varied across studies. Future study will investigate cerebral LFOs in patients with cerebral impairment and evaluate their cerebral autoregulation capabilities and neurocognitive functions via the quantification of LFO phase shifts.

This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements.

Noncontact diffuse correlation tomography (ncDCT) is an emerging technology for 3D imaging of deep tissue blood flow distribution without distorting hemodynamic properties. To adapt the ncDCT for imaging in vivo breast tumors, we designed a motorized ncDCT probe to scan over the breast surface. A computer-aided design (CAD)-based approach was proposed to create solid volume mesh from arbitrary breast surface obtained by a commercial 3D camera. The sources and detectors of ncDCT were aligned on the breast surface through ray tracing to mimic the ncDCT scanning with CAD software. The generated breast volume mesh along with the boundary data of ncDCT at the aligned source and detector pairs were used for finite-element-method-based flow image reconstruction. We evaluated the accuracy of source alignments on mannequin and human breasts; largest alignment errors were less than 10% in both tangential and radial directions of scanning. The impact of alignment errors (assigned 10%) on the tumor reconstruction was estimated using computer simulations. The deviations of simulated tumor location and blood flow contrast resulted from the alignment errors were 0.77 mm (less than the node distance of 1 mm) and 1%, respectively, which result in minor impact on flow image reconstruction. Finally, a case study on a human breast tumor was conducted and a tumor-to-normal flow contrast was reconstructed, demonstrating the feasibility of ncDCT in clinical application.

Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor is within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor blood flow contrasts. In vivo imaging results from two breast carcinomas show higher average blood flow contrasts (5.9- and 10.9-fold) in the tumor regions compared to the surrounding tissues, which are comparable with previous findings using diffuse correlation spectroscopy. The ncDCT system has the potential to image blood flow distributions in soft and vulnerable tissues without distorting tissue hemodynamics.

Occlusion calibrations and gating techniques have been recently applied by our laboratory for continuous and absolute diffuse optical measurements of forearm muscle hemodynamics during handgrip exercises. The translation of these techniques from the forearm to the lower limb is the goal of this study as various diseases preferentially affect muscles in the lower extremity. This study adapted a hybrid near-infrared spectroscopy and diffuse correlation spectroscopy system with a gating algorithm to continuously quantify hemodynamic responses of medial gastrocnemius during plantar flexion exercises in 10 healthy subjects. The outcomes from optical measurement include oxy-, deoxy-, and total hemoglobin concentrations, blood oxygen saturation, and relative changes in blood flow (rBF) and oxygen consumption rate (rV˙O2). We calibrated rBF and rV˙O2 profiles with absolute baseline values of BF and V˙O2 obtained by venous and arterial occlusions, respectively. Results from this investigation were comparable to values from similar studies. Additionally, significant correlation was observed between resting local muscle BF measured by the optical technique and whole limb BF measured concurrently by a strain gauge venous plethysmography. The extensive hemodynamic and metabolic profiles during exercise will allow for future comparison studies to investigate the diagnostic value of hybrid technologies in muscles affected by disease.

Significant drops in arterial blood pressure and cerebral hemodynamics have been previously observed during vasovagal syncope (VVS). Continuous and simultaneous monitoring of these physiological variables during VVS is rare, but critical for determining which variable is the most sensitive parameter to predict VVS. The present study used a novel custom-designed diffuse correlation spectroscopy flow-oximeter and a finger plethysmograph to simultaneously monitor relative changes of cerebral blood flow (rCBF), cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: r[HbO 2 ]/r[Hb]/rTHC ), and mean arterial pressure (rMAP) during 70 deg head-up tilt (HUT) in 14 healthy adults. Six subjects developed presyncope during HUT. Two-stage physiological responses during HUT were observed in the presyncopal group: slow and small changes in measured variables (i.e., Stage I), followed by rapid and dramatic decreases in rMAP, rCBF, r[HbO 2 ] , and rTHC (i.e., Stage II). Compared to other physiological variables, rCBF reached its breakpoint between the two stages earliest and had the largest decrease (76±8% ) during presyncope. Our results suggest that rCBF has the best sensitivity for the assessment of VVS. Most importantly, a threshold of ∼50% rCBF decline completely separated the subjects from those without presyncope, suggesting its potential for predicting VVS.

We report a novel noncontact diffuse correlation spectroscopy flow-oximeter for simultaneous quantification of relative changes in tissue blood flow (rBF) and oxygenation (Δ[oxygenation]). The noncontact probe was compared against a contact probe in tissue-like phantoms and forearm muscles (n = 10), and the dynamic trends in both rBF and Δ[oxygenation] were found to be highly correlated. However, the magnitudes of Δ[oxygenation] measured by the two probes were significantly different. Monte Carlo simulations and phantom experiments revealed that the arm curvature resulted in a significant underestimation (~−20%) for the noncontact measurements in Δ[oxygenation], but not in rBF. Other factors that may cause the residual discrepancies between the contact and noncontact measurements were discussed, and further comparisons with other established technologies are needed to identify/quantify these factors. Our research paves the way for noncontact and simultaneous monitoring of blood flow and oxygenation in soft and vulnerable tissues without distorting tissue hemodynamics.

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs′) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼ 8 mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland–Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5%±2.2% (94.4% to 100.0%) in phantom experiments and 92.8% in the forearm test. The relatively lower limit of agreement observed in the in vivo measurements (92.8%) is likely due to heterogeneous reactive responses of blood flow in different regions/volumes of the forearm tissues measured by different probes. The low-cost compact DSCF device holds great potential to be broadly used for continuous and longitudinal monitoring of blood flow alterations in ischemic/hypoxic tissues, which are usually associated with various vascular diseases.

Technologies currently available for the monitoring of electrical stimulation (ES) in promoting blood circulation and tissue oxygenation are limited. This study integrated a muscle stimulator with a diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively quantify muscle blood flow and oxygenation responses during ES. Ten healthy subjects were tested using the integrated system. The muscle stimulator delivered biphasic electrical current to right leg quadriceps muscle, and a custom-made DCS flow-oximeter was used for simultaneous measurements of muscle blood flow and oxygenation in both legs. To minimize motion artifact of muscle fibers during ES, a novel gating algorithm was developed for data acquisition at the time when the muscle was relaxed. ES at 2, 10, and 50 Hz were applied for 20 min on each subject in three days sequentially. Results demonstrate that the 20-min ES at all frequencies promoted muscle blood flow significantly. However, only the ES at 10 Hz resulted in significant and persistent increases in oxy-hemoglobin concentration during and post ES. This pilot study supports the application of the integrated system to quantify tissue hemodynamic improvements for the optimization of ES treatment in patients suffering from diseases caused by poor blood circulation and low tissue oxygenation (e.g., pressure ulcer).

We employ a hybrid diffuse correlation spec- troscopy DCS and near-infrared spectroscopy NIRS monitor for neonates with congenital heart disease n=33. The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow rCBFDCS; and oxygen metabolism rCMRO2. Concur- rent measurements with arterial spin-labeled magnetic resonance imaging rCBFASL-MRI, n=12 cross-validate rCBFDCS against rCBFASL-MRI, showing good agreement R=0.7, p=0.01. The study demonstrates use of NIRS- DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population. © 2010 Society of Photo

Four very low birth weight, very premature infants were monitored during a 12 degrees postural elevation using diffuse correlation spectroscopy (DCS) to measure microvascular cerebral blood flow (CBF) and transcranial Doppler ultrasound (TCD) to measure macrovascular blood flow velocity in the middle cerebral artery. DCS data correlated significantly with peak systolic, end diastolic, and mean velocities measured by TCD (p(A) =0.036, 0.036, 0.047). Moreover, population averaged TCD and DCS data yielded no significant hemodynamic response to this postural change (p0.05). We thus demonstrate feasibility of DCS in this population, we show correlation between absolute measures of blood flow from DCS and blood flow velocity from TCD, and we do not detect significant changes in CBF associated with a small postural change (12 degrees ) in these patients.

Diffuse optical methods were used to monitor two different therapies in K1735 malignant mouse melanoma tumor models: anti-vascular therapy and radiation therapy. Anti-vascular therapy induced acute variation in hemodynamic parameters within an hour, and radiation therapy induced longitudinal changes within 2 weeks. During anti-vascular therapy, the drug Combretastatin A-4 3-O-Phosphate (CA4P, 2.5 mg/200 mul PBS/mouse) significantly decreased tissue blood flow (65%) and blood oxygenation (38%) one hour after injection. In the longitudinal study, single-fraction ionizing radiation (12 Gy x 1) induced significant reduction of tissue blood flow (36%) and blood oxygenation (24%) 14 days after radiation. The results correlated well with contrast enhanced ultrasound, tumor histology, and a nitroimidazole hypoxia marker (EF5). The research provides further evidence that noninvasive diffuse optical spectroscopies can be useful tools for monitoring cancer therapy in vivo.

We combine diffuse optical spectroscopy DOS and dif- fuse correlation spectroscopy DCS to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is dem- onstrated. Within the first week of treatment day 7 DOS revealed significant changes in tumor/normal contrast compared to pretreat- ment day 0 tissue concentrations of deoxyhemoglobin rctHHbT/N =69±21%, oxyhemoglobin rctO2HbT/N=73±25%, total hemo- globin rctTHbT/N=72±17%, and lipid concentration rctLipidT/N =116±13%. Similarly, DCS found significant changes in tumor/ normal blood flow contrast rBFT/N=75±7%on day 7 with respect to day 0. Our observations suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms. © 2007 Society of Photo-Optical Instrumentation Engi

We have employed near-infrared optical methods to mea- sure 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 infor- mation about blood oxygenation. Ten healthy subjects and one pa- tient with peripheral arterial disease (PAD) were studied during 3-min arterial cuff occlusion of arm and leg, and during 1-min plantar flex- ion 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 ;4.7 fold increase in relative blood flow (rBF) was significantly lower than the corresponding increase in rVO2 (;7 fold). The magnitudes of rBF and rVO2 during exercise in the PAD patient were ;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 simul- taneously measuring rBF and StO2 . The instrument thus provides a method for evaluation of microcirculation and muscle metabolism in patients with vascular diseases. © 2005 Society of Photo-Optical Instrumentation

Purpose: To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy. Experimental Design: Diffuse correlation spectroscopy (DCS) was used to measure blood flow continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5 mg/kg)/PDT (75 mW/cm2, 135 J/cm2). Relative blood flow (rBF; i.e., normalized to preillumination values) was compared with tumor perfusion as determined by power Doppler ultrasound and was correlated with treatment durability, defined as the time of tumor growth to a volume of 400 mm3. Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2). Results: DCS and power Doppler ultrasound measured similar flow decreases in animals treated with identical protocols. DCS measurement of rBF during PDT revealed a series of PDT-induced peaks and declines dominated by an initial steep increase (average ± SE: 168.1 ± 39.5%) and subsequent decrease (59.2 ± 29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow reduction rate; range, 4.4 -45.8% minute−1) of the decrease correlated significantly (P = 0.0001 and 0.0002, r2 = 0.79 and 0.67, respectively) with treatment durability. A positive, significant (P = 0.016, r2 = 0.50) association between interval time and time-to-400 mm3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO2 were predictive (P ≤ 0.015) of treatment durability. Conclusion: These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.

Laser-speckle flowmetry was used to characterize activation flow coupling after electrical somatosensory stimulation of forepaw and hindpaw in the rat. Quantification of functional activation was made with high transverse spatial (μm) and temporal (msec) resolution. Different activation levels and duration of stimulation were quantitatively investigated, and were in good agreement with previous laser-Doppler measurements. Interestingly, the magnitude but not the overall shape of the response was found to scale with stimulus amplitude and the distance from the activation centroid. The results provide new insights about the spatial characteristics of cerebral blood flow response to functional activation, and the method should lead to improved understanding of the coupling of neuronal activity and hemodynamics under normal and pathologic conditions.

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 (p0.05). Patterns of rBF also differ among groups. After both exercises, rBF tend to occur at depressed levels among severe PAD patients compared with healthy (p0.05); post-treadmill, rBF tend to occur at elevated levels among healthy compared with severe PAD patients (p0.05). 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.

A noncontact diffuse correlation spectroscopy (DCS) probe has been developed using two separated optical paths for the source and detector. This unique design avoids the interference between the source and detector and allows large source-detector separations for deep tissue blood flow measurements. The noncontact probe has been calibrated against a contact probe in a tissue-like phantom solution and human muscle tissues; flow changes concurrently measured by the two probes are highly correlated in both phantom (R(2)=0.89, p10(-5)) and real-tissue (R(2)=0.77, p10(-5), n=9) tests. The noncontact DCS holds promise for measuring blood flow in vulnerable (e.g., pressure ulcer) and soft (e.g., breast) tissues without distorting tissue hemodynamic properties.

Arterial revascularization in patients with peripheral arterial disease (PAD) reestablishes large arterial blood supply to the ischemic muscles in lower extremities via bypass grafts or percutaneous transluminal angioplasty (PTA). Currently no gold standard is available for assessment of revascularization effects in lower extremity muscles. This study tests a novel near-infrared diffuse correlation spectroscopy flow-oximeter for monitoring of blood flow and oxygenation changes in medial gastrocnemius (calf) muscles during arterial revascularization. Twelve limbs with PAD undergoing revascularization were measured using a sterilized fiber-optic probe taped on top of the calf muscle. The optical measurement demonstrated sensitivity to dynamic physiological events, such as arterial clamping/releasing during bypass graft and balloon inflation/deflation during PTA. Significant elevations in calf muscle blood flow were observed after revascularization in patients with bypass graft (+48.1 ± 17.5%) and patients with PTA (+43.2 ± 11.0%), whereas acute post-revascularization effects in muscle oxygenation were not evident. The decoupling of flow and oxygenation after revascularization emphasizes the need for simultaneous measurement of both parameters. The acute elevations/improvements in calf muscle blood flow were associated with significant improvements in symptoms and functions. In total, the investigation corroborates potential of the optical methods for objectively assessing the success of arterial revascularization.

"Diffuse correlation spectroscopy" (DCS) is a technology for non-invasive transcranial measurement of cerebral blood flow (CBF) that can be hybridized with "near-infrared spectroscopy" (NIRS). Taken together these methods hold potential for monitoring hemodynamics in stroke patients. We explore the utility of DCS and NIRS to measure effects of head-of-bed (HOB) positioning at 30 degrees , 15 degrees , 0 degrees , -5 degrees and 0 degrees angles in patients with acute ischemic stroke affecting frontal cortex and in controls. HOB positioning significantly altered CBF, oxy-hemoglobin (HbO(2)) and total-hemoglobin (THC) concentrations. Moreover, the presence of an ipsilateral infarct was a significant effect for all parameters. Results are consistent with the notion of impaired CBF autoregulation in the infarcted hemisphere.

We used a nonimpact inertial rotational model of a closed head injury in neonatal piglets to simulate the conditions following traumatic brain injury in infants. Diffuse optical techniques, including diffuse reflectance spectroscopy and diffuse correlation spectroscopy (DCS), were used to measure cerebral blood oxygenation and blood flow continuously and noninvasively before injury and up to 6 h after the injury. The DCS measurements of relative cerebral blood flow were validated against the fluorescent microsphere method. A strong linear correlation was observed between the two techniques (R = 0.89, p < 0.00001). Injury-induced cerebral hemodynamic changes were quantified, and significant changes were found in oxy- and deoxy-hemoglobin concentrations, total hemoglobin concentration, blood oxygen saturation, and cerebral blood flow after the injury. The diffuse optical measurements were robust and also correlated well with recordings of vital physiological parameters over the 6-h monitoring period, such as mean arterial blood pressure, arterial oxygen saturation, and heart rate. Finally, the diffuse optical techniques demonstrated sensitivity to dynamic physiological events, such as apnea, cardiac arrest, and hypertonic saline infusion. In total, the investigation corraborates potential of the optical methods for bedside monitoring of pediatric and adult human patients in the neurointensive care unit.

Introduction Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM. Methods Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value. Results Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion. Conclusions Our results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.