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

Posted Jan 31, 2014 Updated Apr 10, 2023
By Daniel J. Rohrbach BS , Daniel Muffoletto MS , Jonathan Huihui , Rolf Saager PhD , Kenneth Keymel BS , Anne Paquette RN BSN , Janet Morgan PhD , Nathalie Zeitouni MD , Ulas Sunar PhD
8 min read

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.

Results

Here, we present preliminary results from our recently developed clinical instrument for patients with NMSC. We quantified optical absorption and scattering, blood oxygen saturation (StO 2 ), and total hemoglobin concentration (THC) with SFDI and lesion thickness with ultrasound. These results were compared to histological thickness of excised tumor sections.

Conclusions

SFDI quantified optical parameters with high precision, and multiwavelength analysis enabled 2D mappings of tissue StO 2 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.

Nonmelanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common human cancer with more than one million cases every year, and the incidence rate has increased dramatically. Although they rarely metastasize, they can present significant morbidity especially for cases in cosmetically sensitive areas, such as the face. The standard of care for NMSCs is usually surgical excision or Mohs micrographic surgery. Tumors may show multifocal, widespread disease, and suspicious lesions at deeper locations may be present. Typically, biopsies are performed to guide surgeons but can be time-consuming and costly, and the analyzed sections may not be representative of the whole tumor. After surgical removal of the tumor, there may still be residual tumor at the margins, which can result in high-recurrence rates. Thus, the surgeon needs to decide on how much to excise and how deep to go during surgery. Surgery can benefit from prior knowledge of size and depth for more accurate lesion removal. An imaging tool that can provide guidance and thereby reduce recurrence rates, operation times, cost, and the need for multiple biopsies would be highly desired.

Depth and size information can also provide useful information for selecting the appropriate therapy. Topical 5-aminolaevulinic acid (ALA)–based photodynamic therapy (ALA-PDT) has become an attractive treatment option especially for cases with multiple sites and large areas . ALA-PDT uses topical application of the prodrug ALA that is converted into the photosensitizer (PS) protoporphyrin IX (PpIX), which is activated by light in the presence of oxygen for local tissue destruction. For superficial NMSCs, ALA-PDT has efficacy close to surgery with sometimes better cosmetic and functional outcomes. However, the efficacy is limited for thicker and deeper tumors . Thus, tumor size information can allow for a better PDT planning.

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Materials and methods

Clinical Spatial Frequency Domain and Ultrasound Imaging Systems

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Figure 1, (a) Picture of the complete instrument at the clinic; (b) detailed picture of spatial frequency domain imaging head ( red box ); and (c) schematic diagram of the imaging head showing the projector module, two charge-coupled device (CCD) cameras, beam splitter, polarizer, and analyzer. Light-emitting diode (LED) light is delivered with a light guide. Four LEDs are switched sequentially. Digital micromirror device generates sinusoidal patterns, pattern projected onto skin surface by projector and reflected signal is detected by CCD cameras.

Figure 2, Quantification of optical properties. (a) Skin-simulating phantoms with increasing absorption and scattering. Results from spatial frequency domain imaging show quantification of (b) scattering and (c) absorption. Values are the mean of each image and error bars are the standard deviation of the pixel values (error bars are not visible because of small variations).

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Quantification of Optical and Vascular Parameters

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Histopathologic Examination

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Results and discussion

Phantom Imaging

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Figure 3, Spatial frequency domain imaging results for patient 1 having basal cell carcinoma. (a) White light picture of the lesion; (b) reflectance image at 590 nm; (c) absorption map; (d) scattering map; (e) and (f) show the StO 2 and total hemoglobin concentration maps, respectively. The dashed line marks tumor boundary. Scale bar corresponds to 2 mm.

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Patient Imaging

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Figure 4, Depth profiling for patient 1. (a) High frequency ultrasound image and (b) H&E staining. Skin surface marked with the red dashed line , depth to the deepest tumor marked with the solid red line , and suspicious areas are marked with red “T”s . Scale bar in (b) corresponds to 3 mm. For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.

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Figure 5, Spatial frequency domain imaging results for patient 2 having squamous cell carcinoma. (a) White light picture of the lesion; (b) reflectance image at 590 nm; (c) absorption map; (d) scattering map; (e) and (f) show the StO 2 and total hemoglobin concentration maps, respectively. The dashed line marks tumor boundary. Scale bar corresponds to 2 mm.

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Figure 6, Depth profiling for patient 2. (a) High frequency ultrasound image and (b) H&E staining. Skin surface marked with the red dashed line , depth to deepest tumor marked with the solid red line , and suspicious areas are marked with red “T”s . Scale bar in (b) corresponds to 2 mm. For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.

Figure 7, Optical property maps at all wavelengths for patient 1 having basal cell carcinoma. The Dashed line marks tumor boundary. Scale bar corresponds to 2 mm.

Figure 8, Optical property maps at all wavelengths for patient 2 having squamous cell carcinoma. The Dashed line marks tumor boundary. Scale bar corresponds to 2 mm.

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Table 1

Reconstructed SFDI and HFUS Parameters for Two Patients (Mean ± Standard Deviation [SD])

Parameter Patient 1 (BCC) Patient 2 (SCC) Tumor Normal_P_ Value Tumor Normal_P_ Value Mean ± SD Mean ± SD Mean ± SD Mean ± SD Optical absorption at 630 nm (cm −1 ) 0.27 ± 0.03 0.21 ± 0.02 <.0001 0.41 ± 0.06 0.32 ± 0.04 <.0001 Optical scattering at 630 nm (cm −1 ) 11.77 ± 1.20 14.97 ± 0.97 <.0001 10.83 ± 2.47 13.77 ± 2.62 <.0001 Optical penetration depth at 630 nm (mm) 3.19 ± 0.51 3.25 ± 0.34 <.0001 2.69 ± 0.73 2.74 ± 0.63 <.0001 StO 2 (%) 82.30 ± 2.75 76.85 ± 6.23 <.0001 83.74 ± 4.95 89.73 ± 2.60 <.0001 THC (mmol) 0.05 ± 0.01 0.03 ± 0.01 <.0001 0.07 ± 0.01 0.08 ± 0.01 <.0001 Max thickness-HFUS (mm) 1.79 ± 0.05 1.86 ± 0.02 Max thickness-Mohs (mm) 1.76 1.87

BCC, basal cell carcinoma; HFUS, high frequency ultrasound; SFDI, spatial frequency domain imaging; SCC, squamous cell carcinoma.

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 21, Issue 2
Journals General Radiology
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