Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy

Abstract

We evaluate Photofrin-mediated photodynamic therapy (PDT) in a phase 2 clinical trial as an adjuvant to surgery to treat peritoneal carcinomatosis. We extract tissue optical [reduced scattering (mu(s)'), absorption (mu(a)), and attenuation coefficients (mu(eff))] and physiological [blood oxygen saturation (%S(t)O2), total hemoglobin concentration (THC), and photosensitizer concentration (c(Photofrin))] properties in 12 patients using a diffuse reflectance instrument and algorithms based on the diffusion equation. Before PDT, in normal intraperitoneal tissues %S(t)O2 and THC ranged between 32 to 100% and 19 to 263 microM, respectively; corresponding data from tumor tissues ranged between 11 to 44% and 61 to 224 microM. Tumor %S(t)O2 is significantly lower than oxygenation of normal intraperitoneal tissues in the same patients. The mean (+/-standard error of mean) penetration depth (delta) in millimeters at 630 nm is 4.8(+/-0.6) for small bowel, 5.2 (+/-0.67) for large bowel, 3.39(+/-0.29) for peritoneum, 5.19(+/-1.4) for skin, 1.0(+/-0.1) for liver, and 3.02(+/-0.66) for tumor. c(Photofrin) in micromolars is 4.9(+/-2.3) for small bowel, 4.8(+/-2.3) for large bowel, 3.0 (+/-1.0) for peritoneum, 2.5(+/-0.9) for skin, and 7.4(+/-2.8) for tumor. In all tissues examined, mean c(Photofrin) tends to decrease after PDT, perhaps due to photobleaching. These results provide benchmark in-vivo tissue optical property data, and demonstrate the feasibility of in-situ measurements during clinical PDT treatments.

The effects of low-level laser therapy in patients with wrist pain: is this Mickey Mouse science?

“…The effect of light scattering raises questions as to the depth of penetration and absorption and internal activation of light. Absorption sensitivity in regards to light is dependent upon tissue chromospheres such as lipids, water, and photosensitizes [19]. Varying body types in regards to human tissue, amount, thickness, and densities of skin, fat, and fascia, will cause light to penetrate to different depths and will require different frequencies to penetrate tissues [6].…”

Prostate PDT dosimetry

“…Changes in tissue oxygenation due to photochemical oxygen consumption during PDT have been observed directly [65,66], and indirectly through their effect on the photobleaching rate [39,[67][68][69][70]. Recent studies have shown that the concentrations of hemoglobin (Hb), HbO 2 , H 2 O, and photosentizers can be determined from absorption measurements [24,[60][61][62][63]71]. In our current prostate protocol, we accomplish this by repeating the absorption measurements described above, but replacing the laser source with a white light source and the photodiode with a spectrograph.…”

“…Techniques have been developed to characterize the tissue optical properties and the light fluence rate in vivo [21,22]. Other optical spectroscopic methods [23,24] have been developed to characterize tissue absorption and scattering spectra, which in term provide information about tissue oxygenation and drug concentration. Fluorescence techniques [25,26] can be used to quantify drug concentration and can provide valuable dynamic information relating to the photobleaching of the photosensitizer and oxygen consumption.…”

In Vivo Tissue Diagnosis for Myocardial Infarction Using Optical Spectroscopy with Novel Spectral Interpretation Algorithms

“…[Hb] can be observed in tumor tissue [29,46,67]. The experimental evaluations show that the central prediction function, derived from the average source-detection separation of the probe geometry, should provide enough accuracy to distinguish variations in [Hb] within this range.…”

“…This can be achieved easily by calibrating the instrument against a standard or a calibration light source without using an intensity- [53,67]. The [Hb] in colon was found to be 0.601 g/dL [46], and was 0.258 g/dL in esophagus [29].…”