Sub-clinical assessment of atopic dermatitis severity using angiographic optical coherence tomography

Abstract

Measurement of sub-clinical atopic dermatitis (AD) is important for determining how long therapies should be continued after clinical clearance of visible AD lesions. An important biomarker of sub-clinical AD is epidermal hypertrophy, the structural measures of which often make optical coherence tomography (OCT) challenging due to the lack of a clearly delineated dermal-epidermal junction in AD patients. Alternatively, angiographic OCT measurements of vascular depth and morphology may represent a robust biomarker for quantifying the severity of clinical and sub-clinical AD. To investigate this, angiographic data sets were acquired from 32 patients with a range of AD severities. Deeper vascular layers within skin were found to correlate with increasing clinical severity. Furthermore, for AD patients exhibiting no clinical symptoms, the superficial plexus depth was found to be significantly deeper than healthy patients at both the elbow (p = 0.04) and knee (p<0.001), suggesting that sub-clinical changes in severity can be detected. Furthermore, the morphology of vessels appeared altered in patients with severe AD, with significantly different vessel diameter, length, density and fractal dimension. These metrics provide valuable insight into the sub-clinical severity of the condition, allowing the effects of treatments to be monitored past the point of clinical remission.

Keywords: (110.4500) Optical coherence tomography; (170.1870) Dermatology; (170.2655) Functional monitoring and imaging; (170.3880) Medical and biological imaging.

Conflict of interest statement

The authors declare that there are no conflicts of interest related to this article.

Figures

Fig. 1

The structure of skin affected by epidermal thickening (Sebaceous glands and sweat ducts omitted for clarity). Vertical arteries and capillaries rise from the deep plexus and form a horizontal network termed the superficial plexus (SP). From this, capillary loops consisting of both rising arterioles and falling venules form hairpin like structures in the dermal papillae. A) An en-face angiographic svOCT image captured at a depth corresponding to the tips of the capillary loops, visible as small dots in the en-face perspective. B) An en-face angiographic svOCT image captured at a depth corresponding to the SP. Large interconnected vessels are visible. The depth of these layers may provide a direct measure of the tissue inflammation.

Fig. 2

The OCT imaging set-up used for this study. A mechanical clamp (A) was used to fix the Vivosight imaging probe (B) into place above the region of interest. The vertical stage of the clamp (C) was then lowered such that the plastic cap (D) gently touched the surface of the skin (E). This plastic cap reduced any lateral (sliding) motion between the probe and the skin. Data was then transferred to the optical processing unit of the OCT system through a cable (F).

Fig. 3

Steps taken to skeletonize and quantify vascular parameters from angiographic data sets. A) En-face mean intensity projection captured from the popliteal fossa site of a healthy participant. White box shows the FOV used for B-G. B) Median filtering step. C) Multiscale Hessian filtering. D) Result of masking B with the “vesselness” data in C. E) Resulting skeleton (Green) overlaid on the masked data. F) Measured vessel diameter at each point along the vessel.

Fig. 4

Automatic measurement of CLD and SPD through consideration of the number of independent (non-connected) skeleton segments as a function of tissue depth. The top row shows the results for a healthy participant at the left cubital fossa: the local maximum (CLD) is located at 42.9μm beneath the skin surface, while the following local minima (SPD) is located at 132.6μm beneath the surface. The bottom row shows the results for a participant with AD (Local EASI = 5.25) at the left cubital fossa: the local maximum (CLD) is located at 89.4μm beneath the skin surface, while the following local minima (SPD) is located at 304.2μm beneath the surface.

Fig. 5

Averaged (n = 50 – acquired at the same location) OCT images of the popliteal-fossa highlighting the reduction of DEJ contrast as epidermal thickness increases. A) OCT image captured from a healthy subject (Local EASI = 0), showing clear delineation of the epidermis and dermis. B) OCT image captured from an uninvolved site on an eczema patient, showing slightly extended rete-pegs and an undulating DEJ. C) OCT image captured from an involved site on a different eczema patient, showing what appears to be inflammatory acanthosis (Long thin epidermal papillae/rete-pegs). D-F) Manually segmented skin layers, for these an observer simply traced the DEJ by eye, which is laborious and potentially subjective. G-I) Automatically segmented skin layers using the algorithm described above. For D-I, red lines are the skin surface / stratum corneum layer. Green coloration represents the epidermis, Yellow-lines are the DEJ and blue coloration represents the dermis.

Fig. 6

A selection of 3D angiographic OCT images projected over a depth range of 40-275μm beneath the skin surface. A-D) Scans from each data set captured from the cubital fossa (Elbow) skin site. E-H) Scans from each data set captured from the popliteal fossa (Knee) skin site. All images are 4x4mm.

Fig. 7

Top) Charts showing differences in the CLD, SPD and epidermal-dermal junction depth at both the cubital fossa and popliteal fossa skin sites for a range of AD severities. Columns: Mean depth. Bars: Standard deviation. Significance was calculated at each skin site independently using a one-way ANOVA followed by the Tukey-Kramer honest significance difference (HSD) test. Significance matrix colors correspond to the measured p-value (p>0.05 - Red, 0.05>p>0.005 - Orange, 0.005>p>0.0005 - Yellow, 0.0005>p - Green). Quoted data set sizes reflect angiography measurements only, as automatic epidermal-dermal junction assessment failed in a greater number of cases (With a bias towards failing in severe AD cases). Cohort sizes for the epidermal-dermal junction values were as follows: (From left to right): n = 9, 12, 14, 7, 9, 18, 13, 5. Bottom) Scatter plots showing the ungrouped SPD as a function of local EASI score, with a negative correlation visible at both sites. 1st degree polynomial fit was generated using all data points (Including healthy data).

Fig. 8

A selection of 2D angiographic OCT images projected over a depth range of ± 30μm around the detected SPD depth, showing morphological differences in the SPD. A-D) Scans from each data set captured from the cubital fossa (Elbow) skin site. E-H) Scans from each data set captured from the popliteal fossa (Knee) skin site. All images are 4x4mm.

Fig. 9

Bar charts showing the variance of quantitative parameters which were automatically extracted from the superficial vascular plexus layer of data sets following the binarization and skeletonization steps outlined in section 2.3. Columns: Mean depth. Bars: Standard deviation. Significance was calculated at each skin site independently using a one-way ANOVA followed by the Tukey-Kramer honest significance difference (HSD) test. H = Healthy, U = Unaffected, M = Mild localized AD, S = Severe localized AD. Numbers at the base of each column correspond to group size (n).