Bruce J. Tromberg

Near infrared transillumination of the maxillary sinuses: Overview of methods and preliminary clinical results

Though sinusitis is a significant health problem, it remains a challenging diagnosis for many physicians mainly because of its vague, non-specific symptomology. As such, physicians must often rely on x-rays and CT, which are not only costly but also expose the patient to ionizing radiation. As an alternative to these methods of diagnosis, our laboratory constructed a near infrared (NIR) transillumination system to image the paranasal maxillary sinuses. In contrast to the more conventional form of transillumination, which uses visible light, NIR transillumination uses light with a longer wavelength which is less attenuated by soft tissues, allowing increased signal intensity and tissue penetration. Our NIR transillumination system is low-cost, consisting of a light source containing two series of light emitting diodes, which give off light at wavelengths of 810 nm and 850 nm, and a charge coupled device (CCD) camera sensitive to NIR light. The light source is simply placed in the patient’s mouth and the resultant image created by the transmittance of NIR light is captured with the CCD camera via notebook PC. Using this NIR transillumination system, we imaged the paranasal maxillary sinuses of both healthy patients (n=5) and patients with sinus disease (n=12) and compared the resultant findings with conventional CT scans. We found that air and fluid/tissue-filled spaces can be reasonably distinguished by their differing NIR opacities. Based on these findings, we believe NIR transillumination of the paranasal sinuses may provide a simple, safe, and cost effective modality in the diagnosis and management of sinus disease.

OPTICAL MONITORING OF TUMOR ANGIOGENESIS BY MODULATED IMAGING: PRELIMINARY RESULTS FROM AN IN VIVO RAT TUMOR MODEL.: 403

Background The modulated imaging (MI) instrument, recently developed in our laboratory, uses patterned illumination and camera-based detection to obtain quantitative subsurface images of the optical properties of biologic tissues over a wide field-of-view. In this study, we have applied the MI system to associate tumor-induced early angiogenesis with the endogenous optical contrasts such as oxy- ([OHb]), deoxy-([RHb]), and total hemoglobin ([THb]) concentrations and water contents. Methods 13,762 MAT-III tumor cells were inoculated in the mammary fat pad of female Fischer 344 rats (≈160 g). The MI system acquired the raw images every other day for a week from the breast tissue surface by projecting the seven spatial frequency patterns of NIR light (wavelengths ranging from 650 to 970 nm). From the raw images, the quantification of [OHb], [RHb], [THb], and water contents and the light scattering were carried out and the image maps of respective chromophores were obtained. Results With the tumor growth, the concentrations of OHb and THb increased and the tissue oxygen saturation also increased whereas the tissue scattering decreased. The representative images are shown below, and the dotted circle shows the approximate site that tumor cells inoculated. Conclusion Our preliminary results show that the MI system can provide the information on early tumor angiogenesis from the endogenous optical signals. We envision that MI can be a useful tool for tumor therapy monitoring in the future.

489 NONINVASIVE IN VIVO MONITORING OF TISSUE HEMOGLOBIN CONTENTS AFTER HEMOGLOBIN-BASED OXYGEN CARRIER INFUSION IN RABBIT HYPOVOLEMIC SHOCK MODEL.

Introduction Despite their oxygen carrying capacities, the efficacy of hemoglobin-based oxygen carrier (HBOC) transfusion has been complicated by several side effects including hemodilution due to high oncotic properties and vasoconstriction from nitric oxide scavenging. Therefore, it is important to monitor in vivo tissue hemoglobin contents (oxy- and deoxyhemoglobin concentrations ([OxyHb], [DeOxyHb]), and tissue oxygen saturation (StO2) to evaluate the physiologic effects of HBOC transfusion. In this study, the feasibility of a noninvasive diffuse optical spectroscopy (DOS) system to monitor in vivo tissue hemoglobin concentrations during HBOC infusion is demonstrated using a rabbit hypovolemic shock model. Material and Methods Hemorrhage and fluid replacement in intubated New Zealand White rabbits (N = 6) was accomplished by 20% blood loss and slow infusion of Hb glutamer-200 (Hb-200) (Oxyglobin, Biopure, 0.5 mL/min). The DOS prototype probe was placed on the right inner thigh muscle of the hind leg to assess concentrations of [OxyHb], [DeOxyHb], total tissue hemoglobin concentration (THC = [OxyHb] + [DeOxyHb]) as well as StO2 during bloodletting and volume expansion. These values were compared against traditional invasive measurements. Serum hemoglobin concentration (sHgb), systemic blood pressure, heart rate, and blood gas were monitored at regular intervals throughout the experiment. Results THC and sHgb during shock and HBOC infusion (Figure 1) demonstrate that DOS was able to detect the restoration of THC in tissue after Hb-200 infusion, while systemic sHgb continued to decrease due to significant hemodilution. DOS also enables measurements of tissue hemoglobin oxygen saturation status from quantification of [OxyHb] and [DeOxyHb]. Conclusion DOS enables noninvasive in vivo monitoring of oxygen carrying capacity during shock and volume expansion with HBOC and renders insight on distribution of artificial blood substitute at the tissue level. FIGURE 1 Fractional changes of THC and sHgb from baseline during hemorrhage and resuscitation using oxyglobin.

490 VALIDATION OF NONINVASIVE IN VIVO DIAGNOSIS OF METHEMOGLOBINEMIA USING DIFFUSE OPTICAL SPECTROSCOPY IN A NEW ZEALAND RABBIT MODEL.

Introduction Broadband diffuse optical spectroscopy (DOS) combines multi-frequency domain photon migration (FDPM) with time-independent near-infrared (NIR) spectroscopy to accurately measure bulk tissue absorption and scattering spectra between 600 and 1,000 nm wavelength. Simultaneous determination of absorption and scattering provides the capability for accurate noninvasive direct measurement of tissue metabolite composition and concentrations. DOS could potentially be used to monitor changes in various metabolic solutes such as methemoglobin (MetHb) and methylene blue concentrations during treatment in vivo. The purposes of this study are to evaluate the feasibility of DOS to noninvasively monitor metabolic events during methemoglobinemia and treatment using methylene blue (MB) in vivo and to validate DOS measurements with on-site co-oximetry. Material and Methods In vivo diagnosis of methemoglobinemia was evaluated in a New Zealand Rabbit model via intravascular injection of sodium nitrite, and the effects were assessed using DOS monitoring with a prototype device constructed in our laboratory. The DOS data were then compared to standard arterial blood measurements of %MetHb using an on-site co-oximeter. Results In vivo MetHb concentration was quantitatively measured by DOS and was compared to %MetHb obtained through arterial blood from an on-site co-oximetry. %MetHb values from DOS and co-oximetry showed a close correlation (r 2 = .902, p < .0001, N = 4) and the quantification of %MetHb by DOS was not influenced by the cross-talk from oxy- and deoxyhemoglobin concentrations (as demonstrated by varying arterial and venous oxygenation). Conclusion Our results demonstrate the feasibility and robustness of noninvasive in vivo optical quantization of methemoglobinemia in tissue using DOS. FIGURE 1 Comparison between %MetHb vaues from DOS and co-oximetry. N = 4. FIGURE 2 Comparison of %MetHb values from DOS and co-oximetry at different doses of NaNO2 and different FiO2.