Keywords

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FormalPara Key Points
  • Optical coherence tomography (OCT) is a relatively novel skin imaging technology that enables detecting and estimating keratinocyte carcinoma and actinic keratoses in vivo.

  • In cryosurgery-treated AK lesions, OCT imaging has shown subclinical vesicle formation in the lesions within twenty minutes after treatment.

  • Studies imply that OCT imaging has a potential as a diagnostic imaging tool in dermatology.

1 Optical Coherence Tomography

Optical coherence tomography (OCT) is an imaging tool that provides real-time, cross-sectional skin images to a depth of up to 2 mm. OCT is based on an interferometric technique that detects reflected or backscattered light from tissue, OCT probes the sample with a beam of light and subsequently lets the reflections interfere with a reference beam originating from the same light source. The interference is identified either by time domain (positioning), spectral domain (spectrally separated detectors), or Fourier domain (distributing different optical frequencies onto a detector array). The images produced are composite images (B-scans) based on individual A-scans, very similar in appearance to ultrasound scans, albeit at a higher resolution. The axial resolution is dependent on the wavelength used and the lateral resolution of the optics. Commercially available equipment provides lateral resolution of <7.5 μm and axial resolution of 5 μm in the vertical images at up to 2 mm depth and en face images with a resolution of up to 3 μm and up to 1 mm depth.

Generally, skin imaging faces some challenges. Firstly, the skin is easily examined by visual inspection which puts greater demands on the skin imaging tool which has to be both quick and easy, yet provide high quality images. Secondly, skin imaging is challenging due to skin morphology and its unfavorable optical qualities. The skin morphology provides an optical challenge because of the scattering characteristics of the skin. Finally, the abundance of tissue poses a problem in its own right.

OCT therefore has a limited penetration depth, but it provides high-resolution images, which places it in the imaging gap between high-frequency ultrasound (deeper penetration – lower resolution) and confocal microscopy (lower penetration – higher resolution). These features, combined with practical ease of use, strongly suggest that the method may have clinical potential.

2 Imaging of Keratinocyte Carcinomas Using Optical Coherence Tomography

The diagnosis of nonmelanoma skin cancer (NMSC) and actinic keratosis (AK), in this chapter referred to as keratinocyte carcinomas, is based on the clinical presentation and a skin biopsy for histological analysis. The clinical diagnosis of keratinocyte carcinoma can be ambiguous, with sensitivity reported around 56–90 pct and the specificity 75–90 pct [1]. A skin biopsy is considered the gold standard for diagnosis of keratinocyte carcinoma, but the biopsy procedure is invasive, sometimes painful, and can lead to scarring. Skin biopsies are therefore not the optimal choice when monitoring a noninvasive treatment.

For destructive treatments with a lower potential for scarring than frank surgery such as cryotherapy, the problem is different. While the potential for scarring is often described as lower, it is not zero, so arguments of non-scarring are less valid. Other practical arguments for cryotherapy can, however, be found elsewhere in this book, and the method is generally used due to speed, efficacy, and cost benefit. It is, however, a destructive method and therefore reliant on pretreatment diagnosis, and here OCT has the potential to provide swift, real-time support of the clinical diagnosis to guide the treatment far better than time-delayed methods. In order to choose the most appropriate therapy, information about the thickness and extent of the lesion is relevant. Traditionally, not only the diagnosis but also the follow-up examination is done by clinical examination and biopsy.

OCT can provide noninvasive imaging of keratinocyte carcinomas. Architectural disarray of the epidermis is an overall characteristic finding in OCT images of these lesions. OCT images of basal cell carcinoma (BCC) often show oval dark areas in the dermis frequently surrounded by a white halo corresponding to BCC islands and surrounding tumor stroma [26]. OCT characteristics of AK are focally thickened epidermis with white streaks and dots representing the dysplastic epidermis and possible hyperkeratoses or scale [7] (Fig. 15.1a, b). OCT imaging is to some degree comparable to standard histopathology, and a high correlation between OCT images and histopathology of BCC has been demonstrated [811]. Size and delineation of superficial lesions can be estimated using OCT. This potentially makes it a useful tool in the monitoring of noninvasive treatments of keratinocyte carcinomas [12, 13]. However, impaired image quality does in some cases impede identification of a lesion during treatment due to the treatment itself.

Fig. 15.1
figure 1

(a) Optical coherence tomography (OCT) image of normal skin taken just adjacent to an actinic keratosis (AK) lesion located on the scalp. White arrows mark the dermoepidermal junction (DEJ). Black arrows mark vessels. (b) OCT image of AK lesion located on the scalp. Vertical white lines mark disruption of layering. Thick black arrow marks characteristic white streak in the epidermis. White arrows mark the DEJ

3 Optical Coherence Tomography Monitoring of Cryotherapy Treatment

OCT imaging of noninvasive treatment modalities has recently been investigated while OCT imaging in connection with invasive treatments like simple excisions and Mohs surgery has been more extensively studied [12, 1417]. Cryosurgery of premalignant lesions like AK is traditionally guided clinically by freeze-thaw time and lateral extent of freezing, and therefore, real-time OCT monitoring of cryo treatment has been thought to potentially improve accuracy and efficacy of the procedure. Unfortunately, the immediate effects of cryotherapy impair OCT imaging of the tissue. Cryotherapy induces an opaque iceball in the tissue, which completely prevents visualization of the treated lesion and the freezing depth [18] (Fig. 15.2ad). The reason for the opacity is that at the OCT wavelength of 1,300 nm, ice is around ten times more absorbing than liquid water. When the tissue freezes the created ice absorbs all of the OCT laser light, and therefore, OCT images of cryotherapy-treated skin only show an impervious frosty white line at the skin surface. Normal OCT imaging depth and resolution reappears in time with the thawing of the tissue. In cryosurgery-treated grade 1 and 2 AK lesions, OCT imaging has showed vesicle formation in the lesions within twenty minutes after treatment [18]. The vesicles were primarily located along the dermoepidermal junction and appeared as dark areas with a maximum height of 0.47 mm (Fig. 15.2ad). The vesicles were subclinical by the time of the post-cryosurgery imaging and could thus only be identified using OCT. A vesiculobullous reaction after superficial cryogen application is an indication of successful treatment of superficial epidermal lesions because the separation of epidermis and dermis enables the shedding of the diseased skin [19].

Fig. 15.2
figure 2

(a) Optical coherence tomography (OCT) image of normal skin taken just adjacent to an actinic keratosis (AK) lesion located on the dorsal side of a hand. White arrows mark the dermoepidermal junction (DEJ). Black arrows mark vessels. (b) OCT image of AK lesion before cryo treatment. Vertical white lines mark disruption of layering caused by thickening of the epidermis. Thick black arrows mark characteristic white streaks in the epidermis. Thin black arrow marks a hair casting a shadow. (c) OCT image taken seconds after cryosurgery. The treatment produces an opaque iceball. (d) OCT image taken 20 min after cryotherapy. Stars mark emerging vesicles along the DEJ. White arrows mark the DEJ. Small black arrow marks a hair casting a shadow

4 Conclusions

The capability of OCT to identify early tissue changes after cryosurgery of AK lesions implies that OCT could potentially be used as a supplementary tool in assessing the effectiveness of cryosurgery, but specific follow-up studies have not yet been performed. Results from a study on OCT imaging of noninvasive photodynamic therapy of keratinocyte carcinomas and AK indicate that subclinical residual lesions could be identified by OCT at 3 months follow-up [13]. OCT may have the potential to influence patient management by enabling early evaluation of treatment effects. Early detection of complete or partial responses to invasive and noninvasive therapies could make for a better planning of treatment, e.g., reducing treatment area, number of treatments, and thereby reducing pain related to re-treatment. In regard to imaging of the skin and monitoring of treatments, OCT is a relatively novel technology and the cryosurgery and follow-up results are based on studies with small sample sizes. In our view the results are promising and the technology has achieved a level of maturation that makes it possible to explore its clinical use on a larger scale. Additional studies focusing on both the use of OCT as a tool for treatment planning and for follow-up after skin cancer treatments are warranted before OCT can be established as an important tool in the daily clinical practice, but until now more than 15 clinical studies imply that OCT imaging does have a potential as a diagnostic imaging tool in dermatology [8, 20, 21].

Essential Tidbits

  • OCT is an imaging tool that provides real-time high-resolution skin images to a depth of up to 2 mm.

  • It has been used in monitoring cryosurgery of AK.

  • OCT imaging has shown subclinical vesicle formation in the lesions within twenty minutes after cryosurgical AK treatment.

  • OCT used in early detection of complete or partial responses to cryosurgery could make for a better planning of treatment.

Actinic keratoses (AK) :

Actinic keratosis (AK) is a UV light–induced premalignant lesion of the skin that may progress to invasive squamous cell carcinoma.

Interferometry :

An interference pattern is produced by splitting a beam of light into two paths, bouncing the beams back and recombining them. In this way, reflected or backscattered light from the tissue is detected. From the resulting interference signal, one can derive the reflectivity profile along the beam axis.

Keratinocyte carcinomas :

The most common type of skin cancer including basal cell carcinoma and squamous cell carcinoma.

Mohs surgery :

A surgical technique. Microscopically controlled surgery used to treat common types of skin cancer like keratinocyte carcinoma.

Optical coherence tomography (OCT) :

An interferometric imaging technique that detects reflected or backscattered light from the tissue.

AK:

Actinic keratoses

BCC:

Basal cell carcinoma

DEJ:

Dermoepidermal junction

NMSC:

Nonmelanoma skin cancer

OCT:

Optical coherence tomography