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Summary

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

Optical coherence tomography (OCT) is a non-invasive, tomographic imaging technique which generates high-resolution in-vivo images up to mid-dermal layers. Due to continuous technological improvements, OCT is moving from research projects into daily dermatological practice. It can complement other imaging methods like high-frequency ultrasound or confocal microscopy. There is a wide variety of indications for OCT. In addition to aiding in the diagnosis and clinical monitoring of inflammatory dermatoses, OCT is a very useful and feasible technique in dermato-oncology.


History

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

The underlying principles of optical coherence tomography (OCT) originated in biotechnology and have been used for measuring and evaluating fiber optic cables. Low-coherence interferometry (LCI), which is the foundation of current OCT technology, allows one-dimensional images to be produced that are comparable to an ultrasound A-scan. This technique was first used medically in 1988 in ophthalmology by Fercher and colleagues for measuring the human eye [1]. Since the optical penetration of the eye is quite good, OCT proved valuable and was further developed; in 1992 in vitro two-dimensional imaging of the eye was performed [2]. The lateral arrangement of axial one-dimensional images makes it possible to obtain two-dimensional images similar to an ultrasound B scan. Fercher and colleagues [3] used OCT to depict the eye in vivo. Since then OCT has developed in ophthalmology from a purely scientific procedure to a widely-used tool in everyday routine diagnostics.

In other areas of medicine as well, such as cardiology, gastroenterology, urology, dentistry, and dermatology, there has been increasing scientific interest in using OCT [4]. Since it was introduced in 1997 by Welzel and colleagues [5] for use in dermatology, the technical requirements and the interpretation of findings have been refined to a point where the technique is may be expected to become part of routine procedure.

Technique

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

OCT is based on the physical principle of interferometry. In interferometry, coherent light waves are projected onto the skin, and the delay as well as the intensity of the reflections are measured based on the interference behavior. The human skin, unlike the eye, is nearly optically opaque. Only certain wavelengths can penetrate the tissue deeply enough to be useful. Yet in the visible and infrared spectral range of 700–1300 nm – the optical window – it is possible to examine the skin using OCT. Thus, the most common lasers are ultrashort pulsed lasers with near-infrared or broad-band light sources (superluminescence diodes). The light waves are often reflected many times by the different structures. Only a small number of photons are directly reflected; these contain the necessary tissue-specific information for imaging. With the aid of a coherence filter (coherence gate), the photons may be detected and visualized. The visualization is accomplished with an interferometer. The reflected, filtered photons of a measurement arm are compared with those of a reference arm. Based on the resulting interference pattern, the length of the relative optical path may be calculated and a one-dimensional depth profile of the skin (amplitude scan mode) produced. Lateral displacement of the measurement beam can allow for two-dimensional images (brightness scan mode) and three-dimensional images (c-scan mode) to be generated. The axial resolution is independent of lateral resolution. Current coherence tomography can achieve average axial resolutions of 3–15 μm with a penetration depth of 1 to 2 mm [6]. The lateral resolution is defined by the spot size of the measurement beam and may also achieve a resolution of < 10 μm.

The images presented in the following were created using the multi-beam OCT Vivosight® (Michelson Diagnostics). The device we used was a Swept-Source-OCT, which is a variant of frequency-based signal processing. The Vivosight® OCT generates images with an axial resolution of < 10 μm and a lateral resolution of < 7.5 μm.

Imaging techniques in dermatology

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

Along with OCT, two other similar imaging modalities are used in dermatology. One is high-frequency ultrasound (HFUS), and the other is confocal laser scan microscopy (LSM). Both generate in-vivo images of the skin, but they differ considerably in terms of maximum image resolution and penetration depth. Basically, as penetration depth increases, maximum resolution decreases (Figure 1).

image

Figure 1. Schematic figure of maximum resolutions and in- depth penetrations of various optical visualization techniques.

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Confocal laser scan microscopy

Unlike OCT and HFUS, confocal laser scan microscopy depicts the tissue in horizontal sections. This technique can obtain lateral resolutions of 0.5–1 μm. Individual cells and sometimes even cellular components may be visualized. The axial resolution is 3–5 μm which corresponds to the slice thickness of normal histological studies. The penetration depth is limited to the epidermis and the upper dermis (papillary layer) with a maximum of 200 μm. LSM may be used to examine 0.5 mm2 areas of the skin with vertical fenestration (along the z-axis). Using lateral displacement (x-axis, y-axis), a series of scans may be combined to create 1 mm2 to 8 mm2 sections [7-9].

The non-invasive technique may thus be used for in-vivo diagnosis of superficial skin changes. One very important use is for evaluating the benign/malignant nature of melanocytic tumors [10, 11]. The resolution of OCT is not great enough for this purpose, so this is a major advantage offered by LSM. It is also possible to differentiate non-melanocytic tumors and determine their lateral spread [12]. In a recently published study on the evaluation of basal cell carcinomas, LSM had a sensitivity of 100 % and a specificity of 88.5 % [13]. Epithelial skin diseases may also be diagnosed. Their course and response to treatment can also be evaluated.

Still, the technique is limited in regard to the evaluation of changes more than 200 μm deep. For visualization of deeper skin layers, OCT and HFUS are superior.

High-frequency ultrasound

High-frequency ultrasound (20 MHz–100 MHz) has long been used in dermatology, especially for in-vivo measurement of the invasion depth of epithelial tumors and for evaluating the dermis and the subcutaneous fat [14]. 20 MHz ultrasound reaches an axial resolution of 80 μm and a lateral resolution of 200 μm as well as a penetration depth of up to 10 mm. Thus, unlike OCT and LSM, the lower portions of the dermis as well as the subcutaneous fatty tissue may be evaluated. In certain regions of the body, musculoskeletal structures may also be visualized. Given the high penetration depth and an acceptable resolution, 20 MHz ultrasound may be used to measure vertical tumor spread. It is particularly suitable for assessing depth or structures > 1.5 mm as the other two techniques have technical limitations. Yet 20 MHz ultrasound does not offer visualization of the epidermis. The depiction of actinic keratosis, for instance, is impossible. In addition, inflammatory infiltrates, basal cell carcinomas, and melanocytic tumors are echo-poor. Thus, the tumor and infiltrate cannot be distinguished from one another.

OCT can achieve resolutions comparable to those obtained with HFUS (100 MHz). Considering the technical effort relative to resolution and contrast, OCT is superior and also more practical for imaging down to the mid-dermis. HFUS provides less specificity than OCT and LSM and is thus less important for the diagnostic classification of skin tumors.

OCT imaging in dermatology practice

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

Current optic coherence tomography is mobile and may be used on any skin site. No preparations or aids are necessary to perform OCT imaging. A flexible hand piece is positioned on the skin. The area is immediately visualized and then image quality and position can be optimally adjusted. An evaluation of findings may be performed directly during the imaging examination. Alternatively, the sectional images may be stored for later assessment of axial or lateral tumor borders. The vertical tissue sections produced by OCT are similar to histological sections and may be readily evaluated after one has become familiar with the technique.

Depiction of healthy skin

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

After a thin, high-density zone, which is an artifact caused by the reflectivity of the skin, the epidermis is the first layer that is visualized. On the ridged palmar and plantar skin, one can differentiate the prominent stratum corneum. Elsewhere, the stratum corneum is too thin to be clearly distinguished from the remainder of the epidermis. The dermis is usually more signal intense (lighter) than the epidermis. The two layers are divided by the dermoepidermal junction (DEJ), which is clearly visible due to the different optical properties of epidermal keratinocytes and dermal collagen connective tissue. The dermal blood vessels may also be visualized as dark structures where there is nearly no signal; the hair follicles and the sebaceous glands may also be seen as more low signal intensity structures (Figure 2).

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Figure 2. OCT (6 mm × 2 mm) of healthy skin of forearm. Bright superficial band due to alteration in refraction index (non-structural) (1); epidermis with slightly heterogeneous texture resulting from diverse cellular content of keratin (A); Dermoepidermal junction featured as hypo-reflective line (between arrows) because of shift in refraction index; papillary layer: brightly marmorated hyper-reflective zone resulting from densely packed collagen fibers (B); reticulated skin: darkly marmorated, highly hypo-reflective zone resulting from loosely packed collagen fibers (C) and numerous vessels (*).

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Applications in dermatology practice

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

In current everyday dermatological practice, OCT is mainly used for the evaluating non-melanocytic epithelial tumors (Tables 1, 2). The most important uses are in diagnosing tumors, planning excisions, and monitoring therapy. To illustrate the uses of OCT in dermato-oncology, the following presents a range of uses based on actual patients.

Table 1. Indications for OCT in dermato-oncology
IndicationOCT resultsAssessment for practice
Basal cell carcinomaBasal cell nests (characteristic hypo-reflective border)Certain entity identification, diagnosis of type, evaluation of lateral borders, planning extent of excision, follow-up, early detection
Squamous cell carcinoma in situ: actinic keratosis, Bowen disease, erythroplasia of QueyratHyper-reflective keratin depositions, acanthotic epidermis; irregular, but intact DEJEntity identification, rule out invasion, certain evaluation of whole lesion, therapy planning, therapy control
Squamous cell carcinoma, invasiveHyper-reflective keratin depositions, acanthotic epidermis, indistinguishable DEJEntity identification, evaluation of invasion depth to ca. 1.5 mm, therapy decision
Malignant melanomaHyper-reflective, icicle-like structures extending into the dermis; indistinguishable DEJEntity identification is impossible, LSM is superior, evaluation of invasion depth to ca. 1.5 mm, therapy planning
Table 2. Percentage distribution of OCT scans in dermato-oncology practice. Data based on analysis of 1,000 scans at six German institutions
IndicationProportion (%)
Basal cell carcinoma56.9
Actinic keratosis16.6
Therapy course, actinic keratosis7.3
Squamous cell carcinoma2.1
Onychomycosis12.8
Tumor thickness (melanoma)0.9
Other indications (e.g., scars, nevi, inflammatory skin disorders, scabies)3.4

Entity differentiation: pigmented basal cell carcinoma or malignant melanoma?

Clinical picture

A 70-year-old woman presented with a lesion (measuring 0.6 x 0.8 cm) on her back which had appeared about 1.5 years earlier (Figure 3a). The patient had a history of basal cell carcinomas (BCC). Clinical inspection and light microscopy were unable to confirm whether the lesion was a nodular pigmented basal cell carcinoma or a nodular malignant melanoma.

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Figure 3. Nodular malignant melanoma on back. Differential diagnosis: pigmented nodular basal cell carcinoma (arrow) (a). OCT (6 mm × 2 mm): nodular malignant melanoma. Missing demarcation between epidermis and dermis. DEJ only visualized at border area of the tumor (between arrows). Hyper-reflective, vertical, icicle-like central structures (*) (b).

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OCT

The DEJ could not be clearly discerned and there were vertical, icicle-like structures as seen in malignant melanocytic processes [15]. Signs of basal cell carcinoma, such as nests of basaloid cells, were not detected (Figure 3b).

Procedure

We suspected that the lesion was a nodular malignant melanoma because the typical features of BCC were absent. With a tumor thickness of > 1 mm on OCT, there was a potential indication for sentinel lymph node marking/excision (SLNE). We obtained histological confirmation and planned for an excision and possible SLNE. The histological findings confirmed the diagnosis of a nodular malignant melanoma with a tumor thickness of 1.9 mm (Breslow).

Evaluation for practice

For pigmented lesions, treatment decisions may not yet be made based solely on OCT. Yet, for such lesions (nodular tumor, partial pigmentation, multiple BCC in the patient's history), OCT presents an option for narrowing down possible diagnoses. Had basaloid cell nests been seen with OCT, a diagnosis of BCC would have been very likely. In this patient, given the suspicion of a malignant melanoma, additional diagnostic procedures were necessary.

Squamous cell carcinoma: invasive or in situ?

Clinical picture

A 75-year-old woman presented with a sharply-bordered, red-brown plaque that was partly crusty; the lesion had appeared a year before on her right shin (Figure 4a). The patient had been given a presumptive diagnosis of Bowen disease. Yet based on the clinical picture and light microscopy results, the possibility of a superficial basal cell carcinoma or possible invasion, i.e., a squamous cell carcinoma, could not be ruled out.

image

Figure 4. Red-brown sharply delineated plaque, appr. 1 × 0.6 cm in diameter on right tibia (arrow) (a). OCT (6 mm × 2 mm): several hyperkeratoses (1); intact DEJ (between arrows); acanthotic epidermis in sections (2) (b).

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OCT

All portions of the DEJ were depicted throughout the lesion. Acanthotic segments and hyperkeratoses were identified. There were no basaloid cell nests or subepidermal abnormalities. OCT confirmed a diagnosis of an epithelial in-situ tumor (Figure 4b).

Procedure

Excision and histological confirmation of the diagnosis of Bowen disease.

Evaluation for practice

Therapy decision; confirmation that there is no invasive behavior anywhere in the lesion.

Penile intraepithelial neoplasia (PIN) or carcinoma of the penis?

Clinical picture

A 55-year-old man with a two-year history of erythema of the glans penis as well as three condylomata acuminata (Figure 5a). Histology of a punch biopsy showed erythroplasia of Queyrat and on immunohistochemistry (high risk) HPV 16 (Figure 5c).

image

Figure 5. Erythroplasia of Queyrat on glans penis (*); condyloma acuminatum (arrow) (a). OCT (6 mm × 2 mm): Gradual transition from tumor (left, 1) to regular mucosa (right, 2). Acanthotic epidermis (*), intact DEJ (between arrows). Abundant dermal vessels (b). Highly acanthotic epithelium (1), intact DEJ and dermis (2) at lesional site. (H&E, original magnification: x10) (c).

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OCT

Acanthotic top epithelial layer; the DEJ was intact and discernible throughout the lesion and invasion was excluded (Figure 5b).

Procedure

Treatment was with imiquimod cream 3 times weekly for 12 weeks; the patient healed fully.

Evaluation for practice

Invasion could be ruled out for the entire lesion; in this patient, topical treatment was appropriate.

Marking excision borders: sclerodermiform basal cell carcinoma

Clinical picture

A 72-year-old woman presented with a two-year history of a lesion on the right nape (Figure 6a). Based on the clinical presentation and histology, a presumptive diagnosis of sclerodermiform basal cell carcinoma was made. Lateral tumor spread could not be evaluated with certainty.

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Figure 6. Sclerodermiform basal cell carcinoma on right side of bridge of the nose (arrow) (a). OCT (6 mm × 2 mm): multiple nests of basaloid cells featuring characteristic palisading of peripheral cells. OCT images at clinical borders elucidate transition of tumor and healthy skin (*nest of basaloid cells) (b).

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OCT

The presence of a basal cell carcinoma was confirmed, and the lateral tumor borders were visualized. The excision was planned based on the evaluation of the lateral borders of the tumor (Figure 6b).

Procedure

Excision of the basal cell carcinoma with minimal excision margins but with histological confirmation of tumor-free margins.

Evaluation for practice

The technique allows detection of tumor components which are not macroscopically visible; a minimal margin of safety may be selected using OCT-based excision planning.

Follow-up and early detection

Clinical picture

A 33-year-old woman came to our clinic in late 2004 with a red nodule on her right cheek. It had already been treated twice with ablative laser. Histology confirmed a solid, nodular basal cell carcinoma. After administering methyl ALA-PDT twice, the results of histology still showed basal cell carcinoma cells. At the end of 2005, an excision in toto was performed. Semi-annual follow-ups revealed no abnormalities. Then, in 2012, a small flesh-colored papule was found at the lower pole of the excision scar (Figure 7a).

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Figure 7. Skin-colored papule at lower pole of scar due to preceding excision, right cheek (arrow) (a). OCT (1.2 mm × 1.4 mm): Single nest of basaloid cells adjacent to DEJ. Nests of basaloid cells can be visualized in some OCT images only (*nest of basaloid cells). OCT image resembles histological section (b). Two nests of basaloid cells (*) (H&E, original magnification: x20) (c).

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OCT

The results of OCT showed multiple basal cell nests; a presumptive diagnosis of recurrent basal cell carcinoma (Figure 7b) was made.

Procedure

Excision of the papule. The results of histology at first did not show any evidence of a recurrent basal cell carcinoma. After communicating with the histologist, the excised material was re-processed, showing a small, bud-like, basaloid proliferation (Figure 7c). Histology confirmed recurrent basal cell carcinoma.

Evaluation for practice

The potential for quickly analyzing multiple sections makes OCT superior to histology.

Summary

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

OCT is a valuable addition to existing diagnostic methods for assessing non-pigmented lesions. The short examination time enables one to quickly obtain a good overview of the lesion, and if there is any uncertainty, the entire process can usually be more closely examined. The ability to visualize deep sections allows for an evaluation of invasiveness and lateral tumor margins. This is especially helpful for planning surgical resection margins.

Melanocytic tumors are another matter, as the inadequate resolution limits their evaluation. Although icicle-like structures have been described in malignant melanomas, these findings are not specific enough [15]. Penetration depth may be determined to a thickness of about 1.5 mm. the invasion depth may be overestimated when there is an accompanying inflammatory infiltrate, For pigmented lesions, diagnostic decisions cannot yet be made based solely on OCT. Confocal LSM is superior as it offers higher resolution than OCT.

On the whole, OCT and LSM are two promising imaging modalities, which complement each other very well in the diagnosis of epithelial tumors (Table 3). These two techniques are a valuable additions to the current dermatological diagnostic armamentarium. For OCT in particular, large studies validating its sensitivity and specificity would be welcome.

Table 3. Comparison of OCT and LSM
Image

In addition to its present use in dermato-oncology, there are also a number of other indications for OCT which are already established in everyday routine practice or which soon may possible (Table 4).

Table 4. Non dermato-oncologic indications in practice
IndicationAssessment for practice
Hair analysisIn-vivo diagnosis of alopecia; follow-up of same hairs; no epilation/shaving needed; results comparable to histology [16]
Nail diagnosisFungal elements may be visualized in the usually homogeneous, low-signal nail plate [17]; currently no differentiation of pathogens; differentiation from inflammatory causes of nail changes such as lichen ruber, psoriasis, atopic dermatitis
Dermatitis and psoriasisNon-invasive, reproducible follow-up controls; standardized measurement of plaques (hyperkeratosis, acanthosis, papillomatosis) [18, 19]; development of assessment scores possible
Autoimmune diseases (e.g., lupus erythematosus)Findings comparable to histology; follow-up controls [20]
Blistering skin disordersDifferentiation between intraepidermal and subepidermal blistering [21]
ParasitosisRapid detection of parasitic pathogens such as scabies and larva migrans; helps in distinguishing uncertain exanthema and differential diagnosis of scabies [22]
Measuring skin when using topical treatmentsAssessment of skin atrophy (epidermis and dermis) in patients taking corticosteroids [23]

Future directions

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References

Today OCT has become an everyday diagnostic technique used in routine dermatology practice. This tool is a valuable addition to other imaging methods which allow in-vivo diagnosis. Although OCT cannot supplant histological studies, it does allow the dermatologist to quickly confirm diagnoses and make specific treatment decisions. OCT is already a very valuable tool for the evaluation of epithelial tumors. The sensitivity and specificity of the procedure still need to be confirmed by larger studies. As experience with OCT grows, and given further developments in the area of biomedical optics, its uses in actual practice will likely continue to expand in the coming years.

References

  1. Top of page
  2. Summary
  3. History
  4. Technique
  5. Imaging techniques in dermatology
  6. OCT imaging in dermatology practice
  7. Depiction of healthy skin
  8. Applications in dermatology practice
  9. Summary
  10. Future directions
  11. References