Spectroscopy (Blood flow, oxygenation, fluorescence)
We constructed a clinical instrument that combined tri-spectroscopy techniques: diffuse correlation spectroscopy (DCS), diffuse reflectance spectroscopy (DRS) and diffuse fluorescence spectroscopy (DFS) for quantifying hemodynamic parameters and fluorescence content during therapies.
Blood Flow Monitoring During Therapy (DCS)
Diffuse Correlation Spectroscopy (DCS) technique is being utilized to monitor blood flow during therapy. When diffusing photons scatter from moving blood cells, they experience phase shifts which cause the intensity of the diffusing light to fluctuate in time. These fluctuations are more rapid for faster moving blood cells (or for tissues with greater numbers of moving blood cells).
It has been shown that g1(r,τ) satisfies the correlation diffusion equation and blood flow related parameter can be extracted by solving this diffusion equation under certain assumptions: It has been shown empirically in several physiological settings that the extracted parameters a DB characterize the blood flow. Here a is generally proportional to tissue blood volume fraction and DB is an “effective” diffusion coefficient for the blood cells. We generally report relative blood flow, rBF, to describe blood flow changes during therapy: rBF is a blood flow parameter measured relative to its pre-treatment value, i.e. rBF = a DB / a DB(baseline). It should be noted that DCS method can quantify absolute blood flow when the instrument is calibrated possibly with other well-established modalities. For example, DCS method was calibrated very recently with Arterial Spin Labeled Magnetic Resonance Imaging (ASL-MRI) to provide blood flow quantities with absolute units of ml/g/min(blood flow and perfusion terminology is used interchangeably).
Preclinical Noncontact Blood Flow Instrument
A basic blood flow instrument has a long coherence length laser (Crysta Laser, Nevada) operating at 785 nm, a photon-counting detector (Perkin-Elmer, Canada), and a custom built autocorrelator board (Correlator.com, New Jersey). The source light is delivered to the tissue by a multi mode source fiber. A single-mode detector fiber is used to collect the light. Photodetector outputs are fed into a correlator board and resulting intensity autocorrelation functions and photon arrival times are recorded by a computer. From the normalized intensity autocorrelation function, the diffuse electric field temporal autocorrelation function is extracted.
Blood Oxygenation Monitoring During Therapy (DRS)
DRS is being used for quantifying blood oxygen saturation and blood volume. As in the figure below, if we do a simple experiment: shine light on our hand with a flashlight we see that some light passes, mainly near infrared red light penetrates where absorption is low. We can see some bone structure, but the image is blurry due to high scattering of light (photons diffuse) in tissue. Because of low absorption photons penetrate deep. If we zoom in near infrared region/window (see Fig), what we see is that main absorption comes from hemoglobin concentrations. Therefore, our technique is mainly sensitive to blood.
After extracting optical absorption parameter by a physical modelling, since we are assuming that this absorption mainly originates from hemoglobin concentrations (Hb, HbO2), we should be able to extract hemoglobin concentrations.
Main aim is to make a transition from physical quantities (absorption coefficient) to physiological quantities (oxygen saturation, blood volume). We can extract physiologically relevant parameters such as blood volume, as summation of oxy and deoxy hemoglobin concentrations (BV = Hb + HbO2). And tissue blood oxygen saturation (StO2) is defined as ratio of oxyhemoglobin concentration to blood volume (StO2 = HbO2/BV). In tumors, blood volume would be a direct measure of angiogenesis. For example, since tumors induce new blood vessels to feed themselves, which end up generally higher blood volume compared to normal tissue surrounding. At the same time, due to high oxygen demand tumors generally have lower oxygen saturation compared to surrounding tissue such as muscle.
References
- Mesquita R.C., Durduran T., Yu G., Buckley E.M., Kim M.N., Zhou C., Choe R., Sunar U., and Yodh A.G. Direct measurement of tissue blood flow and metabolism with diffuse optics. Phil. Trans. R. Soc. A. 369: 4390-4406 (2011).
- Sunar U, Rohrbach D, Rigual N, Tracy E, Keymel K, Cooper MT, Baumann H, and Henderson B. Monitoring photobleaching and hemodynamic responses to HPPH-mediated photodynamic therapy of head and neck cancer: a case report. Opt Express 18, 14969-14978 (2010).
- Sunar U, Quon H, Durduran T, Zhang J, Du J, Zhou C, Yu G, Choe R, Kilger A, Lustig R, Loevner L, Nioka S, Chance B and Yodh AG. Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: A pilot study. J. Biomed. Opt., 11(6): p.064021 (2006).
- Becker T. L, Paquette A. D., Keymel K. R., Henderson B. W., and Sunar U. Monitoring blood flow responses during topical ALA-PDT. Biomed. Opt. Express 2:123-130 (2010).
- Sunar U, Makonnen S, Zhou C, Durduran T, Yu G, Wang HW, Lee W and Yodh AG. Hemodynamic responses to antivascular therapy and ionizing radiation assessed by diffuse optical spectroscopies. Opt. Express 15:15507-15516 (2007).