Renzhe Bi

Deep tissue flowmetry based on diffuse speckle contrast analysis

Diffuse correlation spectroscopy (DCS) is an emerging modality for noninvasive deep tissue blood flow monitoring that is becoming increasingly popular; it conducts an autocorrelation analysis of fast fluctuating photon count signals from a single speckle. In this Letter, we show that the same level of deep tissue flow information can be obtained from a much simpler analysis on the spatial distribution of the speckles that is obtained by a CCD camera, which we named diffuse speckle contrast analysis (DSCA). Both the flow phantom experiment and in vivo cuff occlusion data are presented. DSCA can be considered a new optical modality that combines DCS and laser speckle contrast imaging (LSCI), which exploits simple instrumentation and analysis and yet is sensitive to deep tissue flow.

Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator

Abstract. Diffuse correlation spectroscopy (DCS) is an emerging noninvasive technique that probes the deep tissue blood flow, by using the time-averaged intensity autocorrelation function of the fluctuating diffuse reflectance signal. We present a fast Fourier transform (FFT)-based software autocorrelator that utilizes the graphical programming language LabVIEW (National Instruments) to complete data acquisition, recording, and processing tasks. The validation and evaluation experiments were conducted on an in-house flow phantom, human forearm, and photodynamic therapy (PDT) on mouse tumors under the acquisition rate of ∼400  kHz. The software autocorrelator in general has certain advantages, such as flexibility in raw photon count data preprocessing and low cost. In addition to that, our FFT-based software autocorrelator offers smoother starting and ending plateaus when compared to a hardware correlator, which could directly benefit the fitting results without too much sacrifice in speed. We show that the blood flow index (BFI) obtained by using a software autocorrelator exhibits better linear behavior in a phantom control experiment when compared to a hardware one. The results indicate that an FFT-based software autocorrelator can be an alternative solution to the conventional hardware ones in DCS systems with considerable benefits.

Multi-channel deep tissue flowmetry based on temporal diffuse speckle contrast analysis

Recently, diffuse speckle contrast analysis (DSCA) was introduced as a competent modality for deep tissue blood flow measurement, where the speckle contrast is calculated over spatial domain on the CCD image of diffuse reflectance. In this paper, we introduce time-domain DSCA where temporal statistics are used for speckle contrast calculation and results in the same deep tissue flow measurement. This new modality is especially suitable for multi-channel real-time flowmetry, and we demonstrate its performance on human arm during cuff occlusion test. Independent component analysis (ICA) study on multi-channel data shows promising results about underlying physiology.

Optical methods for blood perfusion measurement—theoretical comparison among four different modalities

Blood perfusion in human tissue can be measured in vivo by means of various optical methods, which seem to be very different from one another. The most prominent examples of them are laser Doppler flowmetry, laser speckle contrast imaging, diffuse correlation spectroscopy, and the most recently developed diffuse speckle contrast analysis. In this paper, we claim that these four seemingly different modalities are examining different aspects of the same entity-the temporal autocorrelation function of scattered photons. We will show how the observables in each modality can be theoretically derived from the temporal autocorrelation function, and will discuss the merits and drawbacks of each modality in its practical use.

Hemodynamic monitoring of Chlorin e6-mediated photodynamic therapy using diffuse optical measurements

Tumor response during photodynamic therapy (PDT) is heavily dependent on treatment parameters such as light dose, photosensitizer concentration, and tissue oxygenation. Therefore, it is desirable to have a real-time hemodynamic monitoring device in order to fine-tune the parameters and improve PDT efficacy. In this paper, such a tumor response monitoring system was built incorporating both frequency domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), which enables concurrent monitoring of tissue oxygenation (StO₂), total hemoglobin concentration (THC) and relative blood flow (rBF). The tumor metabolic rate of oxygen (TMRO₂) was calculated by using the hemodynamic parameters. Mouse models bearing xenograft tumors were subjected to chlorin e6 (Ce6)-mediated PDT, and the four parameters were monitored with varying treatment conditions. The results show (1) At 3 h post-PDT, rStO₂, rBF and rTMRO₂ exhibited sharp PDT-induced decreases in responders (>40% reduction in tumor volume). Statistically significant difference between responders and non-responders were observed in rStO₂ and rBF, but not in rTMRO₂. (2) Non-responders show gradual recovery of rStO₂, rBF and rTMRO₂ from ∼24 h post-PDT, while responder group did not show recovery up until 48 h post-PDT. Long-term study results up to 2 weeks are also shown. It suggests the hybrid diffuse optical system is not only capable of real-time treatment monitoring, but also able to extract tumor metabolic rate of oxygen to provide more insights about therapy mechanism. Translation of this technique to the clinic will make a quick prognosis feasible and help with treatment optimization.

Fast and Affordable Diffuse Optical Deep-Tissue Flowmetry

Assessing the level of microcirculation on the human body is of paramount importance in clinics because direct measurement of blood perfusion gives information about tissue viability at specific locations. Large-vessel blood flow (macrocirculation), measured by duplex ultrasound or angiograph, does not tell us whether or not the wound will heal.

Coherent backscattering cone shape depends on the beam size.

Coherent backscattering (CBS) is a beautiful physical phenomenon that takes place in a highly scattering medium, which has potential application in noninvasive optical property measurement. The current model that explains the CBS cone shape, however, assumes the incoming beam diameter is infinitely large compared to the transport length. In this paper, we evaluate the effect of a finite scalar light illumination area on the CBS cone, both theoretically and experimentally. The quantitative relationship between laser beam size and the CBS cone shape is established by using two different finite beam models (uniform top hat and Gaussian distribution). A series of experimental data with varying beam diameters is obtained for comparison with the theory. Our study shows the CBS cone shape begins to show distortion when beam size becomes submillimeter, and this effect should not be ignored in general. In biological tissue where a normal large beam CBS cone is too narrow for detection, this small beam CBS may be more advantageous for more accurate and higher resolution tissue characterization.

Deep Tissue Hemodynamic Monitoring Using Diffuse Optical Probes

To see what is happening under our skin using light would have been a dream, as there are many strong absorbers and scatterers that act as hindrances for imaging purpose. Although light penetrates the skin a little and it is possible to image and monitor superficial blood flow using light illumination, it remains as a challenge to probe deep tissue (roughly 0.1 ~ 3.0 cm) using light alone. In this chapter, we describe the challenges and recent achievements of diffuse optical methods to probe deep tissue, running the gamut from diffuse optical spectroscopy (DOS) and diffuse optical tomography (DOT) to recently developed diffuse speckle contrast analysis (DSCA). Diffuse optics has opened up a new possibility of non-invasive diagnosis of lesions in deep tissue. In addition, the usage of light makes diffuse optics-based device compatible with other conventional medical devices such as CT and MRI as well as some implanted device such as pace maker. Moreover, diffuse optics-based device is relatively cost-effective and portable. These merits could limitlessly extend its application to primary care unit, bedside monitoring, and operation theater as an optimal modality for probing hemodynamic parameters in microvasculature in deep tissue.

Frontal Activation Assessment Using Near-Infrared Spectroscopy and Electroencephalography

Here, we focus on assessing frontal activation of normal subjects in response to verbal fluency test. A multimodal instrument, combining NIRS and EEG, was used. The results lead to a better understanding of brain functionality.