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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.

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography.

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.

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning "1") for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89 ± 0.15, 2.26 ± 0.13, and 2.43 ± 0.13 (mean ± standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (p0.001), indicating a gradual recovery of flap vascularity after the tissue transfer. By contrast, rBF changes observed from the unsuccessful flaps were 1.14 and 1.34, respectively, on postoperative days 2 and 4, indicating less flow recovery. Measurement of BF recovery after flap anastomosis holds the potential to act early to salvage ischemic flaps.

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.

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

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 novel near-infrared (NIR) diffuse correlation spectroscopy (DCS) for tumor blood flow measurement is introduced in this review paper. DCS measures speckle fluctuations of NIR diffuse light in tissue, which are sensitive to the motions of red blood cells. DCS offers several attractive new features for tumor blood flow measurement such as noninvasiveness, portability, high temporal resolution, and relatively large penetration depth. DCS technology has been utilized for continuous measurement of tumor blood flow before, during, and after cancer therapies. In those pilot investigations, DCS hemodynamic measurements add important new variables into the mix for differentiation of benign from malignant tumors and for prediction of treatment outcomes. It is envisaged that with more clinical applications in large patient populations, DCS might emerge as an important method of choice for bedside management of cancer therapy, and it will certainly provide important new information about cancer physiology that may be of use in diagnosis.

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.

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.

This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/-7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.