First-in-human pilot study of a spatial frequency domain oxygenation imaging system

Abstract

Oxygenation measurements are widely used in patient care. However, most clinically available instruments currently consist of contact probes that only provide global monitoring of the patient (e.g., pulse oximetry probes) or local monitoring of small areas (e.g., spectroscopy-based probes). Visualization of oxygenation over large areas of tissue, without a priori knowledge of the location of defects, has the potential to improve patient management in many surgical and critical care applications. In this study, we present a clinically compatible multispectral spatial frequency domain imaging (SFDI) system optimized for surgical oxygenation imaging. This system was used to image tissue oxygenation over a large area (16×12 cm) and was validated during preclinical studies by comparing results obtained with an FDA-approved clinical oxygenation probe. Skin flap, bowel, and liver vascular occlusion experiments were performed on Yorkshire pigs and demonstrated that over the course of the experiment, relative changes in oxygen saturation measured using SFDI had an accuracy within 10% of those made using the FDA-approved device. Finally, the new SFDI system was translated to the clinic in a first-in-human pilot study that imaged skin flap oxygenation during reconstructive breast surgery. Overall, this study lays the foundation for clinical translation of endogenous contrast imaging using SFDI.

Figure 1

Clinical imaging system working in the spatial frequency domain: (a) Schematics of the system showing the light paths for all wavelengths into the system imaging head. The light from the NIR light source is propagated to the DMD and projected onto the field through polarizer #1. Light is then collected though polarizer #2 and split onto the three cameras using dichroic mirrors. Wavelengths shown in green and red are collected by NIR cameras 1 and 2, respectively. (b) Picture of the clinical imaging system composed of a cart containing the NIR light source, control electronics, computer, mast, and arm holding the adjustable imaging head. (c) Computer-aided design semi-transparent drawing of the illumination section of the imaging head. Note white light LED modules and the DMD projection module. (d) Bottom view of the actual illumination section of the imaging head. Note the white light LED modules, the DMD projection optics, and the cone aperture.

Figure 2

Laser diode-based NIR light source: (a) Schematics of the NIR light source. Note the wavelength modules composed of one laser diode, a TEC with its heatsink, and an FC coupler. The wavelength modules are combined through a 12-to-1 fiber bundle. (b) Picture of the actual NIR laser light source with the top cover removed. Note the wavelength modules and the fiber bundle.

Figure 3

Venous occlusion of skin flap in Yorkshire pig: Top images: Color images before, during occlusion, and after release, at t = 0, 20, and 30 min, respectively, and over the entire time course. Note a purple discoloration of the tissue during occlusion as blood pools in the tissue. The Vioptix probe can be seen at the bottom right corner of the image. Bottom images: Oxygen saturation images before, during occlusion, and after release, at t = 0, 20, and 30 min, respectively, and over the entire time course. Note the significant decrease in saturation of the right flap during the occlusion. Results are representative of N = 3 separate animals. Top graph: Comparison of SFDI and Vioptix oxygenation measurements as a function of time. SFDI oxygenation saturation values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). Bottom graph: Concentrations of oxyhemoglobin (ctO₂Hb, red) and deoxyhemoglobin (ctHHb, blue) measured using the imaging system as a function of time. Concentration values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). (Video 1, QuickTime, 1 MB). .

Figure 4

Venous occlusion of bowel in a Yorkshire pig: Top images: Color images before, during occlusion, and after release, at t = 0, 12, and 20 min, respectively, and over the entire time course. Note a purple discoloration of the tissue during occlusion as blood pools in the tissue. The Vioptix probe can be seen at the bottom right corner of the image. Bottom images: Oxygen saturation images before, during occlusion, and after release, at t = 0, 12, and 20 min respectively, and over the entire time course. Note the significant decrease in saturation during the occlusion. Results are representative of N = 3 separate animals. Top graph: Comparison of SFDI and Vioptix oxygenation measurements as a function of time. SFDI oxygenation saturation values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). Bottom graph: Concentrations of oxyhemoglobin (ctO₂Hb, red) and deoxyhemoglobin (ctHHb, blue) measured using the imaging system as a function of time. Concentration values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). (Video 2, QuickTime, 0.74 MB).

Figure 5

Vascular occlusion (arterial and venous) of liver in a Yorkshire pig: Top images: Color images before, during occlusion, and after release, at t = 0, 13, and 20 min, respectively, and over the entire time course. Note a purple discoloration of the tissue during occlusion as oxyhemoglobin is converted to deoxyhemoglobin in the tissue. The Vioptix probe can be seen at the bottom right corner of the image. Bottom images: Oxygen saturation images before, during occlusion and after release, at t = 0, 13, and 20 min, respectively, and over the entire time course. Note the significant decrease in saturation during the occlusion. Results are representative of N = 3 separate animals. Top graph: Comparison of SFDI and Vioptix oxygenation measurements as a function of time. SFDI oxygenation saturation values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). Bottom graph: Concentrations of oxyhemoglobin (ctO₂Hb, red) and deoxyhemoglobin (ctHHb, blue) measured using the imaging system as a function of time. Concentration values are averaged over a region of interest (black square in SFDI images). Standard deviation of SFDI measurements within the region of interest is also plotted (gray bars). (Video 3, QuickTime, 1 MB).

Figure 6

Discrimination of venous versus arterial occlusion by SFDI: Comparison of oxygen saturation (stO₂, top), oxyhemoglobin (ctO₂Hb, middle), and deoxyhemoglobin (ctHHb, bottom) during venous (blue) or arterial (red) skin flap occlusions in Yorkshire pigs.

Figure 7

First-in-human pilot study of SFDI in women undergoing breast reconstruction after mastectomy: Columns, from left to right, include: abdominal skin flaps after preparation (left and right sides), right skin flap after elevation, and right skin flap after attachment (transplantation). The first row presents a color image of the flap, the second row the concentration of oxyhemoglobin (ctO₂Hb), the third row the concentration of deoxyhemoglobin (ctHHb), and the fourth row the oxygen saturation images (stO₂).