Lotte Themstrup

Dynamic Optical Coherence Tomography in Dermatology

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions

BACKGROUND Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL-PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours. OBJECTIVES To describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC lesions. METHODS A total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment. RESULTS All lesions displayed at least one OCT characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology. CONCLUSIONS Our study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy

To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome.

In vivo, micro-morphological vascular changes induced by topical brimonidine studied by Dynamic optical coherence tomography.

Brimonidine is a selective α2 adrenergic receptor agonist with potent vasoconstrictive activity topically used for treatment of facial flushing and erythema caused by rosacea. Direct evidence for the in vivo morphology changes in skin vessels induced by topical application of brimonidine is limited. Dynamic optical coherence tomography is a novel technology that combines conventional OCT with information on flow and thereby provides supplementary information about the microvasculature. Dynamic OCT is non‐invasive and creates high‐resolution in vivo images of skin to a depth of maximum 2 mm.

Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin

OBJECTIVES Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. METHODS 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. RESULTS The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. CONCLUSION This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Diagnostic accuracy of optical coherence tomography in actinic keratosis and basal cell carcinoma.

BACKGROUND Early diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. OBJECTIVE The objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. METHODS A study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ®, Michelson Diagnostics, UK). RESULTS Skilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. CONCLUSIONS The study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis.

Cryosurgery treatment of actinic keratoses monitored by optical coherence tomography: a pilot study.

Background: Optical coherence tomography (OCT) is a non-invasive optical imaging technique providing high-resolution images. OCT may be useful as a monitoring tool during treatment of actinic keratoses (AK) and skin cancer. Objective: To examine and describe how OCT skin morphology changes when the tissue is exposed to the effects of cryotherapy. Methods: Normal ex vivo skin and in vivo AK lesions were examined. Cryotherapy was applied and OCT images were acquired at defined time points. OCT morphology was described. Results: Cryotherapy treatment produced an opaque iceball, and freezing depth could not be monitored by OCT. Vesicle formation after cryotherapy could be identified in OCT images. In ex vivo skin no vesicle formation occurred. Conclusion: OCT cannot monitor the freezing depth, but OCT was able to visualise AK lesions and vesicle formation shortly after cryotherapy. Results add to the assumption that OCT could be used in monitoring non-invasive treatments.

Imaging of collagen deposition disorders using optical coherence tomography

Collagen deposition disorders such as hypertrophic scars, keloids and scleroderma can be associated with significant stigma and embarrassment. These disorders often constitute considerable impairment to quality of life, with treatment posing to be a substantial challenge. Optical coherence tomography (OCT) provides a non‐invasive, easily applicable bedside optical imaging method for assessment of the skin. It is hypothesized that OCT imaging may be useful in assessing fibrosis to avoid additional biopsies that could potentially worsen the scarring.

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

Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel morphology and distribution. The potential of D-OCT as a diagnostic tool in dermatology is examined and may give rise to future studies on D-OCT, which are needed to confirm the aforementioned features.

Dynamic Optical Coherence Tomography Capillaroscopy: A New Imaging Tool in Autoimmune Connective Tissue Disease

Importance Vasculopathy characterized by functional and structural abnormalities of the microcirculation plays an important role in systemic sclerosis and dermatomyositis. Although there are several advantages in using capillaroscopy, the method does not offer insight on the skin architecture, flow status, or morphology of the deeper dermal vessels. Dynamic optical coherence tomography (D-OCT) is a recently developed OCT technique that enables detection of high-speed changes in back-scattered light caused by moving cells in vessels. The high resolution of OCT enables the detection of the papillary loops. Objective To explore the potential for OCT capillaroscopy of the nailfolds using D-OCT. Design, Setting, and Participants In this case series study of 4 participants, the nailfolds in 2 patients with systemic sclerosis, 1 patient with dermatomyositis, and a healthy volunteer were scanned using D-OCT. The included patients were all outpatients from the department of dermatology at Bispebjerg Hospital. Data were analyzed from November 2015 to February 2016. Main Outcomes and Measures Dynamic OCT capillaroscopy revealed a potential for imaging of the capillary morphology, the surrounding skin architecture, and flow status of the capillaries in the nailfold. Moreover, D-OCT quantified evident changes of the blood flow in normal nailfold capillaries after application of nitroglycerine and brimonidine. Results This case series included 4 adult women. The quantitative measurements of the blood flow in the D-OCT images of the healthy participant showed significant quantitative differences in blood flow before and after application of nitroglycerine (mean difference, 0.035; 95% CI, 0.008-0.061; P = .02) and brimonidine (mean difference, -0.015; 95% CI, -0.082 to -0.039; P < .001). In the dermatomyositis patient, the en face D-OCT images showed a striking detailed Y-shaped dilated capillary correlating with the clinical finding. In the 2 patients with systemic sclerosis, D-OCT depicted megacapillaries, as well as loss of capillaries. Moreover, cross-sectional OCT images demonstrated a characteristic loss of distinct dermo-epidermal junction and more compact dermis with loss of adnexal structures. Conclusions and Relevance Compared with conventional capillaroscopy, D-OCT offers second-to-none information on nailfold capillary morphology, overall skin architecture, as well as quantitative data on vascular abnormalities and blood flow in the nailfold in a single scan.