Optical coherence tomography
Optical coherence tomography uses near-infrared low-power laser light reflection interference to create images of live tissues, producing images that resemble ultrasound images. This imaging technique was initially developed in the field of ophthalmology, in an effort to provide non-invasive microscopic imaging of the cornea. The resolution vs penetration ratio of OCT stands in between ultrasonography and confocal microscopy, ie 3-10 m resolutions at up to 2 mm depth. Penetration in see-through organs such as the nail or the eye is deeper, but may require different beam focus. Importantly, cutaneous OCT image resolution is too low to allow the analysis of single cell morphology, in contrast to confocal microscopy. Hence, it does not allow the identification of cellular subtypes or cellular atypia. However, it enables live analysis of clusters of cells within the dermis, and is therefore particularly suited for the diagnosis and classification of Basal Cell Carcinomas. The skin can be analyzed both in a horizontal and vertical view. A recent advance, dynamic OCT, enables the examination of blood vessels and red blood cells in real-time motion, a useful tool for the diagnosis of melanoma.
An important advantage of OCT is its ease of use. It does not require any skin preparation and is perfectly safe as the laser beam is low-power. Diagnosis can be made on the spot as images are formed instantly. Moreover, there are no limitations to the number of optical biopsies that can be performed, as it is painless and scar free. There is no need to pick an area of a lesion to biopsy, as the entire lesion can be visualized, thus diminishing the risk of false-sub-typing of the lesion. Finally, OCT can speed up patient care tremendously as the procedure is faster than performing a biopsy and there is no need to wait for the pathology report. Hence, adequate therapy can be started faster.
OCT can be used to diagnose cutaneous cancers, infectious disease and inflammatory diseases. It is well suited to map skin tumors and optimize both nonsurgical and surgical treatment of cancerous lesions. Finally, it can be used as a follow up tool to diagnose relapses or the effect of treatments. The OCT is also used in cosmetology to evaluate skin hydration, wrinkles, skin absorption of different creams and many other applications.
Existing devices (alphabetical order): Agfa healthcare offers a time domain high definition OCT called Skintell. It has a lateral and axial resolution of 3 µm. The field of view is 1.8 x 1.5 mm. The imaging depth is up to 1 mm. Michelson diagnostic offers VivoSight, a swept-source multi beam frequency domain OCT using four beams of light. It has a <7.5 µm lateral resolution and a <5 µm axial resolution. The scanned area is 6 x 6 mm. The image depth is up to 2 mm depending on the skin type. Thorlabs sells a few different spectral domain (SD) OCT of which Callisto is the most suitable for dermatology. They offer three types of lens with lateral resolution 4, 8,12 µm and an axial resolution of <7 µm. The field of views are 6 x 6 mm, 10 x 10 mm, and 16x16 mm. The maximal imaging depth is 1.7 mm.
Torso and head: The change in refractive indexes between the air and the skin induces a thin bright signal that sits atop the epidermis and often induces a slight shadow (Normal Skin: back). The epidermis appears darker, heterogenous and granular due to the different intracellular keratin contents. Underneath the epidermis, the papillary dermis appears as brighter layer, due to packed collagen and a minimal fluid content. Clearly identifying the dermal-epidermal layer is a sign of healthy skin. Finally, the deepest and darkest layer is the reticular dermis. Its hyporeflective feature is owed to the high fluid content from tissue fluid perfusion and vessels combined with the progressive loss of signal due to light scattering incurred in the other layers. In healthy skin, vessels have a tendency to stay at an even plane.
Hair follicles and sebaceous glands can also be visualized. Hair shafts are identified as long thin structures protruding from the epidermis that project a shadow on the epidermis (Normal Skin: hair 1). Their appearance change if they are in the observation plane or not (Normal Skin: hair 2). The hair follicles are situated in the prolongation of the hair and appear as triangular hyporeflective structure with the apex facing the epidermis. The upper part of the associated sebaceous glands can be visualized as hyporeflective ovoid structures connected to the hair matrix (Movie: hair).
Palmar and plantar skin. In OCT, the normal palmar and plantar skin shows, under the hyper-refractile air-epidermis junction, a two-tone epidermis, consisting of a dark grey stratum corneum and a lighter gray (more refractile) stratum granulosum/spinosum/basale, which are separated by a thin dark slit corresponding to the stratum lucid (Normal Skin: palm 1 and Movie: palm 1). This regular architecture is interrupted by sweat glands canal that appear as hyper-reflective vertical corkscrew structures regularly passing through the entire epidermis. They are easily distinguishable in the thickened stratum corneum of hairless skin. In the horizontal view of plantar skin sweat glands can be observed as hyper-reflective dots along dermatoglyphics (Im_NS_foot_1). The papillary dermis appears less dense.
Nail. The nail is extremely well suited for an OCT examination due to its intrinsic optical characteristics, ie light permissive. The OCT enables visualization of the nail morphology and its thickness. Both of which are often altered in dermatological diseases. The healthy nail appears as a trilaminar signal dense structure composed of different scattering parallel layers. (Im_NS_Nail)
Benign skin tumors
a. Seborrheic Keratosis
Marked thickening of the epidermis with a papillomatous aspect showing hypodense structures which possibly correspond to horn pseudocysts. There is also a signal attenuation over the dermis. (Forsea, A. M., Carstea, E. M., Ghervase, L., Giurcaneanu, C., & Pavelescu, G. (2010). Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study. Journal of medicine and life, 3(4), 381.)
Bright hyper-refective dermal structures arranged in thick bundles corresponding to hyalinized collagen bundles in the mid dermis. As well as hyperkeratosis and orthokeratosis. These lesions are more easily studied using HD-OCT. (Picard, A., Long-Mira, E., Chuah, S. Y., Passeron, T., Lacour, J. P., & Bahadoran, P. (2016). Interest of high-definition optical coherent tomography (HD-OCT) for non-invasive imaging of dermatofibroma: a pilot study. Journal of the European Academy of Dermatology and Venereology, 30(3), 485-487.)
c. Warts and condylomas
Dr. Romanelli P. et al studied a verrucae with the OCT to describe the following diagnostic criterias: papillary projections creating the classic architecture, peripheral dermal-epidermal junction thickness (?waiting on Adam) and dilated capillaries in the dermal papilla. (Billero, V., Aldahan, A., & Romanelli, P. (2017, June). The common wart: Comparing optical coherence tomography to histopathology to assess complementary and definitive diagnostic efficacy. In JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (Vol. 76, No. 6, pp. AB250-AB250). 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA: MOSBY-ELSEVIER.)
ii. Condylomas (work in progress)
i. Port wine stain:
The vessels are dilated showing a beaded, snake-like appearance that is adjacent to the dermal-epidermal junction. It is a highly anastomotic vascular network. The epidermis is also more roughly defined when compared to normal skin. (Aldahan, A. S., Chen, L. L., Tsatalis, J. P., & Grichnik, J. M. (2017). Optical Coherence Tomography Visualization of a Port-Wine Stain in a Patient With Sturge–Weber Syndrome. Dermatologic Surgery, 43(6), 889-891.)
Cavernous and tortuous vessels present as oval to round signal poor areas delineated by a signal rich stroma. (Mogensen, M., Thrane, L., Jørgensen, T. M., Andersen, P. E., & Jemec, G. B. (2009). OCT imaging of skin cancer and other dermatological diseases. Journal of biophotonics, 2(6-7), 442-451.)
Actinic keratosis, Bowen and SCC
1. Actinic skin
The normal epidermis of the face shows regular irregularity of the epidermis and dermis that produce a mountain-landscape-like or boulder-like appearance (Im_face_1). In contrast, sun-damaged or aged skin appears as particularly homogeneous and flat / desert-like (Im_face_2).
2. Actinic keratosis
The epidermis is slightly thickened and characterized by poor signal and irregular bands due to hyperkeratosis (Im_AK_Bowen_1). The round signal-free structures seen in the dermis correspond to dilated blood vessels. (Forsea, A. M., Carstea, E. M., Ghervase, L., Giurcaneanu, C., & Pavelescu, G. (2010). Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study. Journal of medicine and life, 3(4), 381.)
3. Bowen/squamous cell carcinoma in situ
The epidermis is markedly thickened, irregular and hypodense. Partially detachable scales are often observed (Im_AK_Bowen_1). Due to the hyperkeratosis and thickening, the signal in the lower parts of the epidermis is often attenuated. This makes analysis of the epidermal disarray, a hallmark of SCC, more challenging. (Forsea, A. M., Carstea, E. M., Ghervase, L., Giurcaneanu, C., & Pavelescu, G. (2010). Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study. Journal of medicine and life, 3(4), 381.)
4. Squamous cell carcinoma
a. Well differentiated early squamous cell carcinoma yields similar images, as expected, to Bowen and SCC in situ. Underneath partially detached scales, the epidermis is markedly thickened, irregular and hypodense (Im_SCC_1). The thicker the SCC, the harder it is to visualize/analyze the lower part of the epidermis. As a result, it is most often impossible to see whether the keratinocytes invade the deep dermis or not. The difference between invasive SCC and non-invasive SCC cannot be made and excision or biopsy is required. Hence, at this stage OCT brings little to the skin specialist in this setting. b. Moderately and poorly differentiated SCC present an ever greater challenge in OCT. OCT does not allow to observe cellular morphology, and the overall morphology of these types of SCC is devoid of clear features. In our experience, images of pseudo-carcinomatosis, granulation tissue and poorly differentiated SCC are very similar, showing dull grey homogeneous tissue with interspersed blood vessels. We still need further research before OCT can helps us in orienting between these clinically relevant diagnosis.
BCC and Gorlin-Goltz syndrome
a. Introduction: OCT is particularly useful for BCC analysis and has been the subject of several seminal and must-read articles. Ulrich et al have for example recently shown that the accuracy of diagnosis for un-pigmented BCC increased from 65.8% with clinical evaluation to 76.2% following additional dermoscopy and to 87.4% with the addition of OCT. Moreover, OCT has been shown by Boone et al. to aid in distinguishing BCC subtypes as relevant for therapeutic choices. Importantly, dermatologist that have been trained in histopathology will have an easy time recognizing vertical OCT images, which remind us of looking to the histology in transparency with the naked eye. Both are insufficient to allow the analysis of cellular morphology, but great big clumps of cells such as those observed in BCC are readily recognizable. Hence, very little training is necessary before one can increase his or her diagnostic accuracy. A frequent mistake is to try and discern cellular morphology, and to look at the images from up close. Actually, standing a few meters from the screen facilitates the analysis of tissue morphology alone. Ulrich M, von Braunmuehl T, Kurzen H, Dirschka T, Kellner C, Sattler E, Berking C, Welzel J, Reinhold U: The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: An observational study. The British journal of dermatology 2015;173:428-435. Boone MA, Norrenberg S, Jemec GB, Del Marmol V: Imaging of basal cell carcinoma by high-definition optical coherence tomography: Histomorphological correlation. A pilot study. The British journal of dermatology 2012;167:856-864. b. Superficial BCC. In vertical images, superficial BCC appears as elliptical pot-bellied protrusion into the dermis (Im_BCC_Superf_01). They are often multiple, giving the impression of inversed strato-cumulus clouds. The protrusion are relatively thin, usually equivalent to the 1-3x the thickness of the normal surrounding epidermis. This thickened epidermis induces a shadow in the underlying dermis. Superficial BCC is often slightly honeycombed/granular compared to the surrounding normal epidermis. Hyaluronic acid containing slits may be visible as non- or weakly refractile areas under the epidermal protrusions, which range between 20 and 100 m (Im_BCC_Superf_02). Importantly, the attachment of the cell clumps to the epidermis is always clear and predominant. As soon as cellular clumps appear as detached from the epidermis, a more aggressive form of BCC (nodular, micronodular or invasive) must be considered for diagnosis. Very often, the epidermis surrounding a superficial BCC is thinner and more flat than normal skin, reflecting actinic changes that, like BCC, are favored by UV-exposure. However, this is not a criterion for the diagnosis in our opinion. Pitfalls: Epidermal thickness may also vary in elder skin. Hair follicle opening may also induce epidermal protrusion that resembles BCC. We observed that dynamic analysis of stacked images often allows to discriminating between random variation of the epidermal thickness as well as facilitating the recognition of hairs follicles (see normal skin section and Vid_BCC_1). In horizontal images of the dermis, superficial BCCs protrusions are easily recognizable, producing flower or bouquet-like patterns of highly refractile cellular clumps. c. Nodular BCC. In nodular BCC, clumps of cells are bigger than those of superficial BCC and protrude deeper into the dermis (Im_BCC_Nod_1). In vertical images, that means that the lower part of the BCC may not be visible. Unlike superficial BCC, the attachment to the overlying epidermis is often lacking, meaning that nodules appear as ovoid structures with dark rims in the dermis (Im_BCC_Nod_2). The signal density varies from signal poor to signal bright depending on their size and localization. The center of large ovoid structure may contain one or several sharply demarcated black areas (ie light permeable/non refractile) yielding a cyst-like appearance (Im_BCC_Nod_3). Pitfalls. Hair follicles cut perpendicular to the hair shaft may also give rise to ovoid structure in the dermis. Dynamic analysis of image stacks most often allows recognizing the hair and thus avoiding over-diagnosis of nodular BCC. d. Invasive (micronodular and sclerodermiform) BCC. Micronodular and sclerodermiform BCC appear as epidermal thickening and epidermal protrusion that dive into the dermis, forming digitiform strands or ovoid nests that are detached from the overlying epidermis (Im_BCC_Inv_1). They are refractile or slightly honeycombed like superficial BCC, can be surrounded by thin dark slits like superficial BCC, yet net separation from the epidermis is always present. We have not yet observed cyst-like areas or big clumps as in nodular BCC. Dynamic analysis of stacked images is particularly helpful to see the spread of digitiform protrusion in the dermis and how they form network-like structures (Vid_BCC_Inv_1). e. Basosquamous BCC. work in progress
2. Gorlin-Goltz syndrome
a. Introduction: Gorlin-Goltz patients can present with dozens when not hundreds of BCC or similar skin lesions. Dermoscopy is a great help for differentiating between superficial BCCs and other BCC forms that require more aggressive treatment. But doubts often remain, especially for lesions recurring after local therapy. Practicing biopsy or excisions of numerous lesions is not always possible or accepted by the patient. OCT offers a much more interesting option, as it allows to painlessly assessing all suspect lesions. b. BCCs in Gorlin-Goltz are the same as BCC of regular patients (see chapter 22.214.171.124. c. Palmar and plantar pits in Gorlin-Goltz. In OCT, the normal palmar and plantar skin shows, under the hyper-refractile air-epidermis junction, a two-tone epidermis, consisting of a dark grey stratum corneum and a lighter gray (more refractile) stratum granulosum/spinosum/basale, which are separated by a thin dark slit corresponding to the stratum lucidum (Im_GorlinGoltz_1 and Mov_GorlinGoltz_1). This regular architecture is interrupted by sweat glands canal that appear as hyper-reflective vertical corkscrew structures regularly passing through the entire epidermis. Palmar pits of Gorlin-Goltz are appear as sharply demarcated areas that completely lack the stratum corneum and lucidum. The remaining layers are significantly thickened and protrude within the surrounding corneum layer (Im_GorlinGoltz_1 and Mov_GorlinGoltz_1). We have never observed signs of underlying BCCs, consistent with the observation that pits do not evolve into locally destructive neoplasias.
Melanoma (work in progress)
Obrigkeit et al demonstrated that fungal elements were detectable as highly scattering elongated structures inside the nail plate at the site of homogeneous signal intensity decrease. Histological analysis permitted to conclude that the high-scattering elements correspond to conglomerates of hyphae and the low scattering areas are due to the surrounding lacunas of the hyperkeratotic nail plate. (Abuzahra, F., Spöler, F., Först, M., Brans, R., Erdmann, S., Merk, H. F., & Obrigkeit, D. H. (2010). Pilot study: optical coherence tomography as a
Scabies (Available soon)
The epidermis is thickened, hypodense and shows elongated protrusions in the underlying dermis. Hyperkeratosis is also present as dark bands with scales protruding leading to a signal attenuation displaying as longitudinal bands. (Forsea, A. M., Carstea, E. M., Ghervase, L., Giurcaneanu, C., & Pavelescu, G. (2010). Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study. Journal of medicine and life, 3(4), 381.)
Work in progress (Im_Eczema_1)