Research ArticleAPPLIED SCIENCES AND ENGINEERING

A paintable phosphorescent bandage for postoperative tissue oxygen assessment in DIEP flap reconstruction

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Science Advances  18 Dec 2020:
Vol. 6, no. 51, eabd1061
DOI: 10.1126/sciadv.abd1061
  • Fig. 1 Comparison of the two tissue oximetry modalities used in this study.

    Left: The current standard of care ViOptix, which relies on the near-IR absorbance of oxy- and deoxyhemoglobin to detect the tissue oxygen saturation %stO2 under the wired lead. Right: A phosphorescence-based approach to tissue oximetry, which uses the phosphorescence of metalloporphyrin painted onto the surface of the skin to map tissue oxygenation. Photo credit: Juan Pedro Cascales, MGH.

  • Fig. 2 Schematic of the DIEP flap reconstructive surgery and postoperative monitoring.

    DIEP flaps taken from the abdomen were used to reconstruct the breast, and postoperative monitoring was performed for 48 hours with two oximeters placed onto each flap as shown: the ViOptix (NIRS, %stO2) and the paintable bandage (phosphorescence, pO2). Photo credit: Juan Pedro Cascales, MGH.

  • Fig. 3 The oxygen-sensing liquid bandage formulation incorporates two dyes into a fast drying commercial liquid bandage and is adherent to the Tegaderm barrier normally used in flap dressings.

    Top: Liquid bandage formulation components: (A) New-Skin brand ethanol-nitrocellulose matrix, (B) in-house synthesized oxygen-sensing metalloporphyrin, and (C) fluorescein reference dye. Bottom: Protocol for liquid bandage application. Bandages are painted on to the inner area of the flaps, allowed to dry for 1 min, and sealed with Tegaderm to prevent interference from room air. After 48 hours of postsurgical measurements, the bandage is removed along with the Tegaderm during redressing. Photo credit: Emmanuel Roussakis, MGH. Schematic adapted with permission from reference (50).

  • Fig. 4 In vitro characterization of the oxygen-sensing bandage and generation of camera calibration curves using bandages painted onto ex vivo human tissue.

    (A) Spectra of the liquid bandage formulation in ethanol demonstrating that only the porphyrin’s emission is oxygen dependent (660-nm peak) and (B) images taken with a cell phone camera of the ethanol formulation under different oxygenation conditions when excited by a 405-nm light-emitting diode flashlight, demonstrating that the red-to-green color change is visible to the naked eye under room lighting. (C) Mean normalized phosphorescence intensity from camera images shown in (E), demonstrating sensitivity to oxygen from 0 to 160 mmHg (gray circle), and that the modified Stern-Volmer relation (I0/I) fits the calibration data (red square). (D) Stern-Volmer calibration with a rolling average applied in both x and y to account for gas flow hysteresis during repeated cycles and (F) demonstration of ex vivo calibrations performed on human breast tissue with different levels of melanin, which had no apparent effect on the sensor performance. Photo credit: Haley Marks, MGH.

  • Fig. 5 Phosphorescence intensity of the bandage is greater than tissue autofluorescence, regardless of skin tone, while still appearing transparent in normal lighting.

    (A) White light– and red-filtered images of the transparent bandage painted onto reconstructed flaps (circled) with inset oxygenation maps for two example subjects with different skin tones. Mean values of the maps over 48 hours for both patients are shown in (B), where the similar scales of the patients’ dynamic oxygenation data further demonstrates that the derivative method acts as a means of self-referencing to each patient’s unique skin properties. Photo credit: Alexandra Bucknor, BIDMC.

  • Fig. 6 Example of temporal oxygenation data throughout 48-hour postsurgical assessment of DIEP flap reconstruction.

    (Patient 2, left breast) Looking at the static phosphorescence (A) and oxygenation (D) readings alongside ViOptix, there is no correlation due to the temporal offset between the signals. However, when looking at the dynamic phosphorescence (B) and oxygenation (E) bandage readings and ViOptix, there is a clear correlation between the two metrics. This is also reflected in the correlation plots shown in (C) and (F) containing all n = 101 observations, revealing a very strong codependency (r = 0.6; P < 0.0001) between first derivatives of pO2 (tissue O2 consumption) and %stO2 (blood O2 delivery) with respect to time, as was found with the developed LMER model.

  • Fig. 7 Compiled temporal data for both oximeters of all subjects’ bandages over the entire 48hour measurement period.

    (A) The inverse correlation between changes in the phosphorescence intensity of the bandage. (B) The changes in bandage oxygenation (pO2) alongside changes in blood oxygen saturation (stO2). Most of the changes in oxygenation occur within the first 10 hours after surgery, which is expected during a reperfusion event, and the temporal trends from the oximeters correlate.

  • Table 1 Equations for the developed LMER models for determining changes in bandage phosphorescence intensity (left) or changes in bandage oxygenation (right) from changes in tissue oxygen saturation.

    NS, not significant.

    Δ % phos = β0 + β1Δ % stO2 + β2t − β3tΔ % stO2 − ϵΔpO2 = β0 + β1Δ % stO2 + β2t − β3tΔ % stO2 − ϵ
    CoefficientValueP valueSignificanceCoefficientValueP valueSignificance
    β02.1530.0036**β0−11.0380.0245*
    β1−1.1978.27 × 10−11***β17.9659.83 × 10−11***
    β2−0.0620.0611.β20.2900.1892NS
    β30.0800.1403NSβ3−0.5580.1239NS
    ϵ−0.056ϵ0.071

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