Imaging Blood Vessel Morphology in Skin: Dynamic Optical Coherence Tomography as a Novel Potential Diagnostic Tool in Dermatology

In structural OCT images, actinic keratoses (AK) show a thickening of the stratum corneum and of the epidermis. All layers can be discriminated from each other and the DEJ is demarcated as a dark line between the epidermis and dermis. There are varying degrees of hyperkeratosis, for example the highly reflecting forms which are often found in thick hyperkeratotic AK, but also variants of hypo-reflection due to parakeratosis. D-OCT depicts the vasculature of AK in the en face view as a reticular pattern with more and slightly larger vessels and in greater disarray compared to healthy skin (Fig. 3a). Thick and thin branching vessels are present [11].

In conventional OCT, Bowen’s disease/squamous cell carcinoma (SCC) in situ have a lot in common with AK, since there is, for example, also a visible increase in epidermal thickness. Typical features like hyperkeratotic scales appear less thick or are even absent. But with D-OCT, it might be possible to differentiate between the two skin tumor entities by the vasculature. The vascular network in Bowen’s disease/SCC in situ has a more grainy appearance with vessels in the form of dots, blobs and sometimes curves, dependent on the skin depth of the image (Fig. 3b). Overall, the dot-like vessels in Bowen’s disease/SCC in situ are larger than in healthy or psoriatic skin.

Invasive SCC, in situ SCC and AK with thick hyperkeratotic scales are very difficult to discriminate with structural OCT images mainly because the hyperkeratosis makes it nearly impossible to get an insight into deeper skin layers and the DEJ is also obscured. In the structural OCT images, the diagnostician has to identify specific characteristics of invasive SCC such as the alteration or loss of the normally visible DEJ as well as the disruption of the dermis and/or of regular skin layers, which can also be noticed in AK/SCC in situ. In the dermis, protrusions from the epidermis invading the dermis show various shapes of different signal intensity. With D-OCT, the dynamic mode adds information on the vasculature to the structural images. The vessels of invasive SCC appear in different irregular forms and patterns on the one hand and show changes in vessel diameters on the other (Fig. 3c).

BCC is the most common skin cancer and also the most frequent non-melanocytic skin cancer. The most important risk factor for BCC is UV irradiation [12]. Initially, the BCC can be clinically detected as small, highly demarcated, translucent or pearly nodules, papules, scars or ulcerations with typical teleangiectasia [12, 13]. There are different subtypes of BCC with associated risks of recurrences [14]. BCC grow slowly, but, in the absence of treatment, the tumor can expand in the vertical as well as the horizontal direction and lead to destruction of tissue or even bones [13]. The rate of metastasis is very low and thus BCCs are sometimes called semi-malignant tumors [12].

In structural OCT, a BCC is apparent as an ovoid hypo-reflective formation with a darker boundary and partially signal-free, cystic parts compared to the surrounding hyper-reflective stroma, or is visible as a lobule-like protrusion of the epidermis. An alteration of the DEJ is also a typical feature of BCC in OCT. Clinically, a BCC can be diagnosed with a sensitivity of 59–90% and a specificity of 75–90%, while with dermoscopy and OCT a precision of 87.4% can be achieved [2, 15]. Nevertheless, it is still difficult to discriminate between BCC subtypes despite a new proposed algorithm in high-definition OCT [16‐19]. As well as for initial diagnosis, OCT is also used for treatment monitoring of BCC [20‐23].

As for every type of tumor, the extension and growth of vessels are essential for the development of non-melanoma skin cancer [24]. Due to angiogenesis, the necessary nutrients and oxygen reach the BCC and help to support its growth. In BCC, there are two known forms of blood vessels. The superficial arborizing vessels, named teleangiectasia, can be recognized in dermoscopy, while in the histopathological examination multifocal superficial BCC are displayed by light tissue and a higher vascularisation in the dermis between the multiple tumor islands [25]. Both the superficial and the deeper vascular networks in the dermis can be seen in the D-OCT images. First, the cross-sectional D-OCT images show extended vertical vessel columns in superficial BCC (Fig. 4a). Second, the en face view visualizes the changes in vessel diameters and the chaotic arrangement of very small irregular vessels (Fig. 4b) [11]. There is a wide range of the vascular network in BCC visible. Some vessels appear larger than those seen in healthy skin and some look so tiny and fragile that they would not have been noticed if they were not depicted in red color. It is obvious that the vessels are mainly located in the center of the BCC, and sometimes it can be seen that the vessels also seem to surround the rims of the tumor nests (Fig. 4b) [6]. The additional information regarding the vessel morphology in BCCs provided by D-OCT may be of value in non-invasively determining the subtype and aggressiveness of the tumour, so that more informed treatment decisions can be made, especially in the context of non-invasive treatment options.

Due to the limitation of the image resolution, it is difficult to evaluate melanocytic lesions in conventional cross-sectional OCT images. However, with D-OCT, it is necessary to observe the vasculature of nevi or melanoma in horizontal or even 3D views.

In nevi with accumulations of melanocytes in the DEJ or in the superficial dermis, the D-OCT shows a homogenous picture like in healthy adjacent skin. Right below the epidermis inside the mole, sharply demarcated vessels regularly organized in the form of dots are visible (Fig. 5a). If there is a deep dermal involvement, then sometimes a delicate reticular pattern can be noticed (Fig. 5b). In a suspected dysplastic lesion, the vessels in the dermis are larger and formed in characteristic curves, reaching from bottom to top with regular frequency. To visualize this aspect, a 3D image must be constructed from the D-OCT dataset. The tumor depth is directly proportional to the length of the bowed vessels.

Because of the intra-epidermal growth of melanomas, the tumors show scattered distributed clusters of vessel dots and even blobs in the superficial dermis (Fig. 5d) [26]. However, the deeper the tumor grows, the more that dots seem to form linear figures (Fig. 5e). Highly invasive melanomas consist of long, intense, linear vessels that are of irregular size and distribution and show a branching pattern (Fig. 5f). The latter is visualized as an arborizing or bulging architecture. Especially in thick, deeply invasive melanomas, the formation of vessel aneurysms and multiple bizarrely and irregularly shaped vessels are apparent. In 3D view, it can be seen that these tumors build ‘spikes’, delicate perpendicular figures, which reach up to the epidermal surface.

Our preliminary results indicate that D-OCT reveals changes in vessel morphology as the lesion progresses from dysplastic nevus to melanoma in situ and then to more invasive melanomas. We therefore speculate that D-OCT might be useful in assessing disease progression leading to earlier/more efficient interventions, and also as a powerful research tool in understanding this disease. Further work is required to confirm these ideas.

In structural OCT in the cross-sectional as well as in the en face views, the pattern of gyri and sulci is one typical criterion of seborrheic keratoses. However, when looking at the vessels, the benign character of the lesion is immediately obvious. There are many regularly distributed dotted, but also curved, and sometimes even coiled vessels corresponding to the hairpin-like vessels, which can also be found in dermoscopy (Fig. 5c).

Psoriatic skin shows hyperkeratosis, acanthosis, pronounced regular rete ridges and dilated vessels in the dermis, demonstrating the components of inflammation, proliferation of the epidermis and angiogenesis, which contribute to the development of psoriasis. All of these features are displayed in structural OCT, but, especially with D-OCT, the typical vessel capillary loops in the papillary dermis, named spikes, are visible (Fig. 6a, b).

In patients with systemic scleroderma, it is known that this disease causes thickening and hardening of the skin and impedes the microcirculation blood supply especially in the fingertips [27‐29]. Ring et al. found out that in structural OCT the typical DEJ is missing and the density of the dermis is enhanced along with a disappearance of the skin appendages [30]. As a result of the loss of blood vessels, the acral parts of the body like the fingertips are no longer supplied with blood leading to necrosis and ulceration. A recent study discovered megacapillaries in the shape of a Y with D-OCT instead of the small vascular network, which can be recognized in healthy nail folds [6, 30] [Fig. 7 comparison of a scleroderma patient (a, b) with a healthy skin fold (c, d)].

The distinction between different types of chronic wounds is often difficult. A biopsy will probably lead to the final diagnosis, but is counterproductive for delayed wound healing. To investigate the healing process, biopsy is not the ideal way to do this, because, once the tissue sample is taken, repeated biopsies are not possible in the same location. Through the use of D-OCT, in vivo insight into the wound with its newly proliferating vessels enables multiple non-invasive “biopsies” from several locations which may provide full monitoring of the continuous wound healing process like no other available device [31, 32].

In particular in chronic venous insufficiency, different stages of vascularisation are visible. The adjacent normal skin in the surrounding area of the ulcer presents large, extended lymphatic vessels without perfusion (Fig. 8a). In dermatosclerotic skin, there is only a minor growth of dotted vessels in the sclerotic and fibrous stroma (Fig. 8b). At the margin of the ulcer, the vessels form dots of higher density (Fig. 8c). In the middle of the wound itself, granulation islands with larger aggregations of vessels in the form of dots, blobs and coils are apparent (Fig. 8d). It might therefore be possible to use D-OCT to assess the healing status of individual ulcers so that ‘chronic’ non-healing ulcers can be quickly identified for earlier intervention than is currently possible.

Moreover, D-OCT may help to evaluate the depth of a burn wound and to determine whether the injury can be treated conservatively or surgically [33‐36]. Besides the structural information on the amount of burned skin, D-OCT shows the remaining and the thermolytically affected blood vessels (Fig. 9a, b). This way, the diagnostician may get an overall impression of the extent of the burn injury by using D-OCT.

Scars are the end result of tissue repair. Thus, there is still a difference between healthy skin and scar tissue. Clinically scars can be painful or itchy; they can be atrophic, hypertrophic or even keloids, which exceed the original scar area with their proliferation. Besides that, scars are distinguishable from normal skin through their color/pigmentation, structure, height in the level of the skin, firmness and pliability. Histopathologically, alterations in the vascular network and in the epidermal structure can be found in scar tissue, but collagen deposits, fibrous tissue remodeling, inflammatory infiltrations and sclerosis might also be present.

All these criteria need to be considered for the evaluation of scars. Nevertheless,only subjective scores are available and objective parameters are missing [37, 38]. Moreover, scars after burn injury were objectively explored with OCT by Gong et al. [37, 39] and Liew et al. [40] through automated quantification of the density and diameter of the vasculature using speckle decorrelation and the attenuation coefficient [37, 39, 40]. The result is that inside the scar tissue the density of blood vessels is increased and that there is no typical vascular network formation like in healthy skin, but a parallel organization of the vasculature (Fig. 10). More effective characterization of scars with D-OCT may lead to more accurate treatments.