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Atopic dermas (AD - Eczema); an inflammatory condion of the skin, currently affects ~10.5% of the populaon, represenng a significant quality of life impairment. Aims Characterizing the microcirculation of atopic dermatitis using angiographic optical coherence tomography. R. Byers , R. Maiti , S. Danby , E. Pang , B. Mitchell , M. Cork and S. Matcher 1 Department of Infection, Immunity & Cardiovascular Disease, The University of Sheffield, UK. 1 Background 1. J. I. Silverberg et al, “Adult eczema prevalence and associations with asthma and other health and demographic factors.“ J. Allergy Clin. Immunol. (2013). 2. T. S. Tang et al, “Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?” J. Allergy Clin. Immunol. (2014). 3. R. A. Byers et al, “High-resolution label-free vascular imaging using a commercial, clinically approved dermatological OCT scanner,” SPIE BiOS. (2016). Biophotonics group Sheffield - RAByers1@sheffield.ac.uk 1 3 3 1 Methods Figure 1 4 AD is typically graded externally using clinically visible symptoms such as erythema, excoriaon and lichenificaon. However subclinical abnormalies within the skin provide key informaon about the condion even past the point of clinical remission. The microcirculaon presents several key subclinical metrics, which have potenal to be correlated with AD progression and used to quanfy response to treatment. Ulise angiographic opcal coherence tomography (OCTA) to capture and compare the morphology of microcirculaon within both healthy skin and skin affected by AD. Extract quantave subclinical metrics from the datasets. In parcular, the use of OCTA to robustly measure the degree of epidermal thickening (Hyperplasia) in AD. 1 2 Pilot study parcipants: References and Acknowledgements The Naonal Research Ethics Service (NRES) Commiee East Midlands–Derby approved the study, under the project reference 04/MREC/70. Furthermore, this research was supported by BBSRC Doctoral Training Grant: BB/F016840/1 and EPSRC grant: EP/K009699/1. The authors also gratefully acknowledge the use of OCT equipment funded by MRC grant: MR/L012669/1. Figure 3 Figure 4 Conclusions Structural measurements of epidermal thickness are challenging in AD paents due to a lack of contrast at the DEJ. OCTA offers a robust alternave method for quanfying the degree of epidermal hyperplasia through consideraon of the vascular layers. Current work is expanding this study to look at the correlaon between clinical score (EASI) and many of the discussed subclinical abnormalies measurable with OCTA. Futhermore, these metrics will be correlated with measures of skin barrier funcon. OCTA is able to differenate between healthy and AD skin through comparison of automacally extracted vessel metrics, including: diameter, length and connecvity. For more informaon, please consult the following paper: 2 3 3 3 Department of Electronic and Electrical Engineering, 2 Department of Mechanical Engineering, 2 5 healthy volunteers with Fitzpatrick skin type between I-III and no history of chronic skin disease. 5 AD volunteers with Fitzpatrick skin type between I-III, and mean severity (EASI) of 8.5 ± 3.3. Scan sites selected as common sites of adult AD: Leſt/right cubital fossa (Inner elbow). Leſt/right popliteal fossa (Rear of the knee). 4x4x2mm OCTA volumes (N=10) captured non-invasively from each skin site using a clinical Vivosight OCT scanner. Notably, subclinical abnormalies are present even at unaffected AD sites (B). Structural OCT views of skin changes resulng from AD. A) OCT image captured from a healthy subject, showing clear delineaon of the epidermis and dermis. B) OCT image captured from an uninvolved site on an eczema paent, showing slightly extended rete-pegs and an undulang dermal-epidermal juncon (DEJ). C) OCT image captured from an involved site on a different eczema paent, showing what appears to be psoriasiform hyperplasia (Long thin epidermal papillae/rete-pegs). D-F) Manually segmented skin layers. The red-line is the skin surface / stratum corneum layer. Green colouraon represents the epidermis, the yellow-line is the DEJ and blue colouraon represents the dermis. Figure 2 Method of quanficaon for epidermal thickness using OCTA. Disnct vessel morphologies of the capillary loop ps (A) and superficial arteriolar plexus (B) allow for a robust esmaon of epidermal thickening. With the depth (A) being a lower bound, and (B) being an upper bound. Depth resolved en-face OCTA images of both healthy & AD skin Top row) Volumes acquired from healthy volunteers at both skin sites. Boom row) Volumes acquired from AD paents at both skin sites. Colours correspond to depth beneath the skin surface: Green colouraon = 117-195μm Red colouraon = 39-117μm Blue colouraon = 195-273μm Capillary loops are visible on both healthy/AD datasets as red/green dots. The SAP is typically visible between 117-195μm for healthy volunteers but is generally absent in cases of AD, suggesng it is deeper in the ssue. A significant increase in SAP depth was measured for AD volunteers at both sites. Comparavely capillary loop depth only increased by a small amount at both sites in cases of AD. These results are indicave of epidermal psoriasiform hyperplasia such as that seen on figure 1C. Comparison of capillary loop depth and SAP depth as a funcon of AD. AD affected skin Figure 5 Significantly higher mean vessel diameter at the popliteal fossa in AD volunteers. Likely indicave of inflammaon. Variaon in quantave vessel parameters as a funcon of AD. Lower vessel connecvity for AD paents at both sites. Suggesng incomplete vessel linkages within the plexus. Significantly lower vessel density and length for AD paents at both sites. Both of these metrics suggest that less vessels are within the field of view (0-300μm depth) for AD cases. Metrics were acquired automacally from maximum intensity projecons of the enre visible OCTA volume. R. Byers et al, “Characterizing the microcirculaon of atopic dermas using angiographic opcal coherence tomography,” SPIE BiOS, 2017. 3

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Atopic dermatitis (AD - Eczema); an inflammatory condition of the skin, currently affects ~10.5% of the population, representing a significant quality of life impairment.

Aims

Characterizing the microcirculation of atopic dermatitis using angiographic optical coherence tomography.

R. Byers , R. Maiti , S. Danby , E. Pang , B. Mitchell , M. Cork and S. Matcher1

Department of Infection, Immunity & Cardiovascular Disease, The University of Sheffield, UK.

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Background

1. J. I. Silverberg et al, “Adult eczema prevalence and associations with asthma and other health and demographic factors.“ J. Allergy Clin. Immunol. (2013).2. T. S. Tang et al, “Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?” J. Allergy Clin. Immunol. (2014).3. R. A. Byers et al, “High-resolution label-free vascular imaging using a commercial, clinically approved dermatological OCT scanner,” SPIE BiOS. (2016).

Biophotonics group Sheffield - [email protected]

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Methods

Figure 1

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AD is typically graded externally using clinically visible symptoms such as erythema, excoriation and lichenification. However subclinical abnormalities within the skin provide key information about the condition even past the point of clinical remission.The microcirculation presents several key subclinical metrics, which have potential to be correlated with AD progression and used to quantify response to treatment.

Utilise angiographic optical coherence tomography (OCTA) to capture and compare the morphology of microcirculation within both healthy skin and skin affected by AD.

Extract quantitative subclinical metrics from the datasets. In particular, the use of OCTA to robustly measure the degree of epidermal thickening (Hyperplasia) in AD.

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2

Pilot study participants:

References and AcknowledgementsThe National Research Ethics Service (NRES) Committee East Midlands–Derby approved the study, under the project reference 04/MREC/70. Furthermore, this research was supported by BBSRC Doctoral Training Grant: BB/F016840/1 and EPSRC grant: EP/K009699/1. The authors also gratefully acknowledge the use of OCT equipment funded by MRC grant: MR/L012669/1.

Figure 3

Figure 4

ConclusionsStructural measurements of epidermal thickness are challenging in AD patients due to a lack of contrast at the DEJ. OCTA offers a robust alternative method for quantifying the degree of epidermal hyperplasia through consideration of the vascular layers.

Current work is expanding this study to look at the correlation between clinical score (EASI) and many of the discussed subclinical abnormalities measurable with OCTA. Futhermore, these metrics will be correlated with measures of skin barrier function.

OCTA is able to differentiate between healthy and AD skin through comparison of automatically extracted vessel metrics, including: diameter, length and connectivity.

For more information, please consult the following paper:

2 3 3 3

Department of Electronic and Electrical Engineering, 2Department of Mechanical Engineering,

2

5 healthy volunteers with Fitzpatrick skin type between I-III and no history of chronic skin disease.5 AD volunteers with Fitzpatrick skin type between I-III, and mean severity (EASI) of 8.5 ± 3.3.

Scan sites selected as common sites of adult AD:Left/right cubital fossa (Inner elbow).Left/right popliteal fossa (Rear of the knee).

4x4x2mm OCTA volumes (N=10) captured non-invasively from each skin site using a clinical Vivosight OCT scanner.

Notably, subclinical abnormalities are present even at unaffected AD sites (B).

Structural OCT views of skin changes resulting from AD.

A) OCT image captured from a healthy subject, 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 dermal-epidermal junction (DEJ). C) OCT image captured from an involved site on a different eczema patient, showing what appears to be psoriasiform hyperplasia (Long thin epidermal papillae/rete-pegs).

D-F) Manually segmented skin layers. The red-line is the skin surface / stratum corneum layer. Green colouration represents the epidermis, the yellow-line is the DEJ and blue colouration represents the dermis.

Figure 2 Method of quantification for epidermal thickness using OCTA.Distinct vessel morphologies of the capillary loop tips (A) and superficial arteriolar plexus (B) allow for a robust estimation of epidermal thickening. With the depth (A) being a lower bound, and (B) being an upper bound.

Depth resolved en-face OCTA images of both healthy & AD skin

Top row) Volumes acquired from healthy volunteers at both skin sites. Bottom row) Volumes acquired from AD patients at both skin sites. Colours correspond to depth beneath the skin surface:

Green colouration = 117-195μmRed colouration = 39-117μm Blue colouration = 195-273μm

Capillary loops are visible on both healthy/AD datasets as red/green dots. The SAP is typically visible between 117-195μm for healthy volunteers but is generally absent in cases of AD, suggesting it is deeper in the tissue.

A significant increase in SAP depth was measured for AD volunteers at both sites. Comparatively capillary loop depth only increased by a small amount at both sites in cases of AD. These results are indicative of epidermal psoriasiform hyperplasia such as that seen on figure 1C.

Comparison of capillary loop depth and SAP depth as a function of AD.

AD affected skin

Figure 5

Significantly higher mean vessel diameter at the popliteal fossa in AD volunteers. Likely indicative of inflammation.

Variation in quantitative vessel parameters as a function of AD.

Lower vessel connectivity for AD patients at both sites. Suggesting incomplete vessel linkages within the plexus.Significantly lower vessel density and length for AD patients at both sites.

Both of these metrics suggest that less vessels are within the field of view (0-300μm depth) for AD cases.

Metrics were acquired automatically from maximum intensity projections of the entire visible OCTA volume.

R. Byers et al, “Characterizing the microcirculation of atopic dermatitis using angiographic optical coherence tomography,” SPIE BiOS, 2017.

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