Preoperative Mapping of Nonmelanoma Skin Cancer Using Spatial Frequency Domain and Ultrasound Imaging

      Rationale and Objectives

      The treatment of nonmelanoma skin cancer (NMSC) is usually by surgical excision or Mohs micrographic surgery and alternatively may include photodynamic therapy (PDT). To guide surgery and to optimize PDT, information about the tumor structure, optical parameters, and vasculature is desired.

      Materials and Methods

      Spatial frequency domain imaging (SFDI) can map optical absorption, scattering, and fluorescence parameters that can enhance tumor contrast and quantify light and photosensitizer dose. High frequency ultrasound (HFUS) imaging can provide high-resolution tumor structure and depth, which is useful for both surgery and PDT planning.


      Here, we present preliminary results from our recently developed clinical instrument for patients with NMSC. We quantified optical absorption and scattering, blood oxygen saturation (StO2), and total hemoglobin concentration (THC) with SFDI and lesion thickness with ultrasound. These results were compared to histological thickness of excised tumor sections.


      SFDI quantified optical parameters with high precision, and multiwavelength analysis enabled 2D mappings of tissue StO2 and THC. HFUS quantified tumor thickness that correlated well with histology. The results demonstrate the feasibility of the instrument for noninvasive mapping of optical, physiological, and ultrasound contrasts in human skin tumors for surgery guidance and therapy planning.

      Key Words

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        • Ericson M.B.
        • Wennberg A.M.
        • Larko O.
        Review of photodynamic therapy in actinic keratosis and basal cell carcinoma.
        Ther Clin Risk Manag. 2008; 4: 1-9
        • Kalka K.
        • Merk H.
        • Mukhtar H.
        Photodynamic therapy in dermatology.
        J Am Acad Dermatol. 2000; 42: 389-413
        • Maytin E.V.
        • Anand N.
        • Baran C.
        • et al.
        Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic.
        Proc SPIE. 2009; 7164 (71640K-9)
        • van den Akker J.T.
        • de Bruijn H.S.
        • Beijersbergen van Henegouwen G.M.
        • et al.
        Protoporphyrin IX fluorescence kinetics and localization after topical application of ALA pentyl ester and ALA on hairless mouse skin with UVB-induced early skin cancer.
        Photochem Photobiol. 2000; 72: 399-406
        • Rhodes L.E.
        • de Rie M.
        • Enstrom Y.
        • et al.
        Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial.
        Arch Dermatol. 2004; 140: 17-23
        • Rhodes L.E.
        • de Rie M.A.
        • Leifsdottir R.
        • et al.
        Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma.
        Arch Dermatol. 2007; 143: 1131-1136
        • Busch T.M.
        • Xing X.
        • Yu G.
        • et al.
        Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.
        Photochem Photobiol Sci. 2009; 8: 1683-1693
        • Zhou X.
        • Pogue B.W.
        • Chen B.
        • et al.
        Pretreatment photosensitizer dosimetry reduces variation in tumor response.
        Int J Radiat Oncol Biol Phys. 2006; 64: 1211-1220
        • Georgakoudi I.
        • Nichols M.G.
        • Foster T.H.
        The mechanism of Photofrin photobleaching and its consequences for photodynamic dosimetry.
        Photochem Photobiol. 1997; 65: 135-144
        • Wilson B.C.
        • Patterson M.S.
        The physics, biophysics and technology of photodynamic therapy.
        Phys Med Biol. 2008; 53: R61-109
        • Henderson B.W.
        • Gollnick S.O.
        • Snyder J.W.
        • et al.
        Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors.
        Cancer Res. 2004; 64: 2120-2126
        • Cuccia D.J.
        • Bevilacqua F.
        • Durkin A.J.
        • et al.
        Quantitation and mapping of tissue optical properties using modulated imaging.
        J Biomed Opt. 2009; 14: 024012
        • Saager R.B.
        • Cuccia D.J.
        • Saggese S.
        • et al.
        A light emitting diode (LED) based spatial frequency domain imaging system for optimization of photodynamic therapy of nonmelanoma skin cancer: quantitative reflectance imaging.
        Lasers Surg Med. 2013; 45: 207-215
        • Azhari H.
        Ultrasound: medical imaging and beyond (an invited review).
        Curr Pharm Biotechnol. 2012; 13: 2104-2116
        • Marmur E.S.
        • Berkowitz E.Z.
        • Fuchs B.S.
        • et al.
        Use of high-frequency, high-resolution ultrasound before Mohs surgery.
        Dermatol Surg. 2010; 36 (official publication for American Society for Dermatologic Surgery): 841-847
        • Schmid-Wendtner M.H.
        • Burgdorf W.
        Ultrasound scanning in dermatology.
        Arch Dermatol. 2005; 141: 217-224
        • Gruber J.D.
        • Paliwal A.
        • Krishnaswamy V.
        • et al.
        System development for high frequency ultrasound-guided fluorescence quantification of skin layers.
        J Biomed Opt. 2010; 15: 026028
        • Moore J.V.
        • Allan E.
        Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control.
        Br J Dermatol. 2003; 149: 1035-1040
      1. Jacques SL, ed. Optics of light dosimetry for PDT in superficial lesions versus bulky tumors. Proc SPIE, 2002; 4612:59-68.

        • Chin C.W.
        • Foss A.J.
        • Stevens A.
        • et al.
        Differences in the vascular patterns of basal and squamous cell skin carcinomas explain their differences in clinical behaviour.
        J Pathol. 2003; 200: 308-313
        • Gioux S.
        • Mazhar A.
        • Cuccia D.J.
        • et al.
        Three-dimensional surface profile intensity correction for spatially modulated imaging.
        J Biomed Opt. 2009; 14: 034045
        • Sunar U.
        • Rohrbach D.
        • Morgan J.
        • et al.
        Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging.
        Biomed Opt Express. 2013; 4: 531-537
        • Saager R.B.
        • Cuccia D.J.
        • Saggese S.
        • et al.
        Quantitative fluorescence imaging of protoporphyrin IX through determination of tissue optical properties in the spatial frequency domain.
        J Biomed Opt. 2011; 16: 126013