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Biomedical subjects

Turgut Durduran

Publications and source records attributed to Turgut Durduran.

11 recordsLinked to original sources

Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy.

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 < or = 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.

Animals↗

Diffuse optical tomography with spectral constraints and wavelength optimization.

We present an algorithm that explicitly utilizes the wavelength dependence of tissue optical properties for diffuse optical tomography. We have previously shown that the method gives superior separation of absorption and scattering. Here the technique is described and tested in detail, and optimum wavelength sets for a broad range of chromophore combinations are discovered and analyzed.

Algorithms↗

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI.

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.

Adult↗

Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation.

We combine diffuse optical and correlation spectroscopies to simultaneously measure the oxyhemoglobin and deoxyhemoglobin concentration and blood flow in an adult human brain during sensorimotor stimulation. The observations permit calculation of the relative cerebral metabolic rate of oxygen in the human brain, for the first time to our knowledge, by use of all-optical methods. The feasibility for noninvasive optical measurement of blood flow through the skull of an adult brain is thus demonstrated, and the clinical potential of this hybrid, all-optical noninvasive, methodology can now be explored.

Adult↗

Spatiotemporal quantification of cerebral blood flow during functional activation in rat somatosensory cortex using laser-speckle flowmetry.

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 (microm) 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.

Animals↗

Uniqueness and wavelength optimization in continuous-wave multispectral diffuse optical tomography.

We derive conditions for the unique and simultaneous recovery of chromophore concentrations and scattering coefficients in multispectral continuous-wave diffuse optical tomography. These conditions depend strongly on measurement wavelengths. We introduce and demonstrate a general methodology for choosing those wavelengths, which yields superior separation of scattering from absorption and superior separation of one chromophore from another. Application of these concepts should significantly improve the fidelity of continuous-wave diffuse near-infrared optical tomography in tissues.

Computer Simulation↗

Transabdominal near infrared oximetry of hypoxic stress in fetal sheep brain in utero.

The feasibility of transabdominal near-infrared (NIR) spectroscopy for detecting and quantifying fetal hypoxia in utero is demonstrated in a pregnant ewe model. A frequency domain NIR spectroscopy probe, consisting of two detectors and six sources operating at three wavelengths (675, 786, and 830 nm), was placed on the maternal abdomen directly above the fetal head. Fetal hypoxia was indirectly induced through occlusion of uterine blood flow for approximately 3 min. NIR photon diffusion measurements were made during a baseline period, during hypoxia of the fetus, and during recovery. Fetal blood samples were drawn from the fetal brachial artery and jugular veins at several time points during the cycle. Seven hypoxic cycles were induced in a total of five pregnant ewes. The NIR measurements were analyzed by using a two-layer diffusion model to deconvolve the fetal blood saturation from that of the pregnant ewe. Fetal hypoxia was detected. Good agreement was found between fetal blood saturation determined by the transabdominal NIR method and arterial and venous fetal blood saturation quantified from fetal blood samples by using a hemoximeter.

Abdomen↗

Frequency-domain multiplexing system for in vivo diffuse light measurements of rapid cerebral hemodynamics.

A novel frequency-domain multiplexing system has been developed for in vivo measurements of rapid cerebral hemodynamics. The instrument operates in the frequency-domain with three optical wavelengths, six source positions, and two detectors. Frequency-division multiplexing was used to modulate three wavelengths (690, 786, and 830 nm) at slightly different frequencies around 70 MHz. The three laser output beams were combined and switched into different source positions by use of fast optical switches (switch time <10 ms). Three narrowband, in-phase and in-quadrature demodulators decode the modulated signals. Our full-frame-acquisition rate is 2.5 Hz, with flexibility for acquisition rates greater than 50 Hz with smaller detection areas. We evaluate the performance of the instrument with tissue phantoms, and then employ the system to measure in vivo cerebral blood oxygenation during forepaw stimulation of a rat's brain.

Animals↗

Diffuse optical measurement of hemoglobin and cerebral blood flow in rat brain during hypercapnia, hypoxia and cardiac arrest.

We have demonstrated the ability to concurrently measure relative changes in cerebral blood flow, hemoglobin concentration, and hemoglobin oxygenation with a single non-contact, non-invasive instrument. Our measurements from rat hypercapnia, hypoxia and cardiac arrest models are in reasonable agreement with the literature, and offer the possibility for further growth and quantification. The optical techniques used in this study are attractive also because they enable experimenters to measure vascular response of deep tissues. The new instrument and concept may also be applicable to human studies especially in infants and neonates permitting noninvasive monitoring of cerebral hemodynamics and oxygen (see [4] and [2] for examples of NIR spectroscopy).

Animals↗

Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia.

Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto(2)), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo(2)). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 +/- 0.04, rCBV = 1.02 +/- 0.04, DeltaSto(2) = -11 +/- 2%, rOEF = 1.39 +/- 0.06 and rCMRo(2) = 0.59 +/- 0.07. Although rOEF increased in response to decreased blood flow, rCMRo(2) decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature.

Animals↗

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.

Adult↗