VivoScene

September 2021 Issue

Video Blog by Jon Holmes, CEO of Michelson Diagnostics Ltd. (MDL)

Our CEO Jon Holmes is commenting on a recent paper [1] describing a method that offers a new patient-centric, non-surgical option with improved efficacy and cosmetic outcomes for the treatment of Basal Cell Carcinoma (BCC).

Skin cancer treatment pioneer Dr. Orit Markowitz is the first to show that adding VivoSight OCT image guidance for BCC lesion margination and recurrence monitoring leads to one year clearance rates, as determined by clinical, dermoscopy and OCT examination, of 98% excluding immunosuppressed patients and 95.8% including immunosuppressed patients. Most lesions cleared with one Nd:YAG laser treatment.

Learn more in the Video Blog here.

 

Jon Holmes, CEO of Michelson Diagnostics Ltd.

“Advanced skin imaging is imperative for our teaching institution”, says Merete Haedersdal, Professor at the University of Copenhagen and Consultant in Dermatology at Bispebjerg Hospital, Copenhagen, Denmark and further visiting scientist to the Wellman Center for Photomedicine in Boston, USA.

“The practice of dermatology has come a long way and without an adequate assortment of imaging systems, we cannot be at a leading edge in research or modern clinical practice.”

At Bispebjerg University Hospital, the academic team in the department associated with skin imaging consists of professors, physicians, residents, clinical and dermatology research fellows and a good group of medical students. At any given moment, these individuals perform skin imaging procedures other than with the ubiquitous dermatoscope (Figs. 1–2).

 

Merete Haedersdal, MD, PhD, DMSc
Fig. 1: Bispebjerg Hospital, Copenhagen, Denmark. Photo courtesy of Nis Kentorp
Fig. 2: Patient being examined with VivoSight OCT

Dr. Haedersdal continues, “in many cases we make use of Reflectance Confocal Microscopy (RCM) and Optical Coherence Tomography (OCT). We just acquired our second VivoSight OCT system and generally use it for the purpose of:

Accelerating Skin Research Projects

  • See skin microstructures, up to > 1 mm deep, and see skin changes produced by disease and treatments
  • Obtain objective structural and vascular measurements, like epidermal thickness – superficial vascular plexus depth, vessel diameter and density – surface roughness – blood flow at various depths – epidermal brightness as a proxy for collagen density and more

Providing Advanced Clinical Practice

  • Quickly see below the surface to better inform treatment decisions
  • Aids in monitoring treatment response
  • Effective communication tool with patients

These areas have almost infinite applicability in a university teaching environment, and I’d like to mention just a few recent examples of our group’s work:

Wenande et al: OCT-imaging utilized for low-risk BCC tumor demarcation, treatment and tumor response assessment [2]

  • For tumor demarcation, imaging appeared beneficial as OCT detected subclinical tumor in 58% of clinical margins, leading to expansion of the treatment area
  • Evaluation of BCC tumor thickness with OCT
  • OCT and RCM used to assess treatment response for potential retreatment
  • OCT utilized to identify best location for post-treatment biopsies

Fuchs et al: Subclinical acne micromorphology and temporal treatment response visualized and quantified [3]

  • High correlation between acne clinical severity and skin imaging features
  • Transfollicular delivery of microparticulate suspension visualized
  • Significant increase in epidermal thickness and vessel morphology changes quantified
  • OCT and RCM identify subclinical imaging biomarkers that may allow treatment triage

Banzhaf et al: Spatiotemporal closure of fractional laser-ablated channels imaged by OCT and RCM [4]

  • VivoSight OCT identifies laser channels as black ablation defects in epidermis and upper dermis, surrounded by a characteristic pattern of hyper- and hyporeflective zones
  • OCT visualizes heterogeneous material in the lower part of open laser channels, indicating tissue fluid
  • Gradual spatiotemporal closure of laser channel observed over time with in-vivo OCT imaging

Ortner et al: OCT useful for morphometric imaging of microporated nail tissue targeted for drug delivery [5]

  • Images from various imaging technologies were assessed for nail plate thickness, micropore dimensions and degree of poration
  • OCT demonstrated the highest repeatability of all imaging techniques
  • Micropore dimensions correlated strongest between OCT and RCM

Another important reason to have top skin imaging capabilities is the expectation of newly arriving medical students, researchers and clinicians. In today’s interconnected world they want to be part of what’s going on around the globe regarding new insights and best practices. Without proper equipment, they’d be locked out from advances at other international sites and we can’t afford that. As such, not only do we stay on top in this field, skin imaging is part of many PhD programs and a good opportunity for researchers and clinicians to differentiate themselves.

In a similar vein, patients become more knowledgeable and, where appropriate, will want to be evaluated in a most convenient way, a characteristic of non-invasive imaging technologies.

Given our focus on laser-assisted (transdermal) drug delivery and on new ways treating various types of skin cancer, a further good example of keeping up with technology is the increased use of Artificial Intelligence (AI) in medical imaging applications including dermatology. This is a timely development for our work within the Danish Research Center for Skin Cancer. A concentrated effort is underway to understand and manage various manifestations of skin cancer better, from diagnosis to treatment. We are excited to be part of the VivoSight OCT AI Working Group that is specifically working on machine learning algorithms to aid in the evaluation of BCC suspicious lesions (Fig. 3).

Fig. 3: Yellow to red to blue areas: different confidence levels for AIaugmented BCC imaging biomarkers.

In summary, advanced skin imaging capabilities are an indispensable element in our department for research efficiency, making discoveries and assessing patients effectively. VivoSight OCT serves us well and we are excited about the AI initiative as well as making imaging a solid discipline in our dermatology department”.

OCT is a valuable tool in clinical dermatology and dermatologic research.

A comprehensive review article by Psomadakis and Markowitz et al. also covers its utility in diagnosis, monitoring, and grading disease severity in a variety of cutaneous conditions.

Potential of monitoring early disease progression and overall vascular health with OCT [7]

Excellent article by Michael Wang-Evers et al. on importance of visualization and quantification of the skin microvasculature, changes of which correlating with age and blood pressure. 

Change in dermal microvasculature after skin compression and immediate release is efficiently imaged and measured by VivoSight OCT (Fig. 4) potentially allowing assessment of overall vascular health and monitoring early disease progression.

Fig. 4: Normal skin microvasculature (top) and after compression with immediate release (bottom)

VivoSight OCT measures vascular characteristics of port wine birthmarks classified by color [8]

Different color Port Wine Birthmark (PWB) vessel characteristics, such as diameter and depth, may impact presentation and treatment outcomes.

It was found that superficial vessels of purple PWB were significantly closer to the epidermis than pink PWB, which might inform selection of more optimal laser treatment parameters.

How deep is the tattoo?

Accumulations of dark tattoo ink can be well seen with OCT to a depth of about 1 mm. Can measurement of tattoo ink depth help to optimize laser tattoo removal protocols?

Dark tattoo ink, about 0.34 mm deep, visualized by VivoSight OCT.
Comparison screen of skin without tattoo (top) and adjacent skin with tattoo (bottom)

Thanks to Brittani Jones for these OCT images. Brittani is a research student for Dr. David Ozog at Henry Ford Health Systems Dermatology Department.

Brittani Jones
David Ozog, MD

PharmaEd Resources’ Microneedle & Transdermal Delivery Systems Summit 2021 brings together leading researchers in the field to share the most recent advances in the design, formulation, and delivery of skin-mediated therapies and vaccines.

VivoSight OCT is utilized at various research sites to visualize microneedle arrays in the skin, measure insertion depth, monitor swelling or dissolution, as well as skin and vascular changes at the treated site, all of which can help to navigate the clinical and regulatory pathway.

Link to Summit: here

Download Program: here

Register: here

VivoSight Artificial Intelligence (AI) Project on Track

As mentioned in previous newsletter editions, VivoSight’s AI initiative is ongoing with more capabilities being developed.

We present a sample image that displays a perceived BCC lesion in various colors representing various confidence levels (Fig. 5).

Fig. 5: Yellow to red to blue areas: different confidence levels for AIaugmented BCC imaging biomarkers.

Dr. Giovanni Pellacani is full professor and chairman of the department of dermatology at Sapienza University of Rome, Italy. To date he has published more than 800 peer reviewed articles.

“One of my research interests is noninvasive imaging for skin cancer. Like any multifaceted area, this requires a set of effective tools that have their unique purpose and complement each other.

We use VivoSight OCT when we need to look deeper than the first about 200 μm, as done with RCM (Reflectance Confocal Microscopy). Imaging as deep as > 1 mm affords us good understanding of depth and lateral extent of NMSC (Non-Melanoma Skin Cancer) lesions and as such gives us a quick global overview whether there are (still) suspicious anomalies.

Further we use OCT not only for NMSC. It is also an effective modality to assess stages of inflammatory and autoimmune disease such as atopic dermatitis, psoriasis and bullous disease.

OCT distinguishes micromorphology of the condition and excellent vascular imaging capabilities add another layer to characterize the pathology, often indicating degree of disease severity including subclinical Fig. 5: Yellow to red to blue areas: different confidence levels for AIaugmented BCC imaging biomarkers. manifestations. We have published several papers on OCT imaging biomarkers describing inflammatory skin conditions [9].

A very important issue is the development of skin imaging standards, methods and measures to efficiently compare treatment effects and patient status [10]. In collaboration with other international thought leaders we home in on imaging biomarkers that allow us to share our results more efficiently. This further includes the development of Artificial Intelligence (AI) based algorithms for VivoSight OCT.

Noninvasive skin visualization will become vital in modern dermatology and the integration of imaging standards will add to the common language describing our work.”

References

1. Markowitz, O, Bressler, MY. Combining Nd:YAG laser with optical coherence tomography for nonsurgical treatment of basal cell carcinoma. Lasers Surg Med. 2021; 1– 8. https://doi.org/10.1002/lsm.23455

2. Wenande, E., Hendel, K., Mogensen, M., Bagger, C., Mårtensson, N.L., Persson, D.P., Lerche, C.M., Husted, S., Janfelt, C., Togsverd-Bo, K., Anderson, R.R. and Haedersdal, M. (2021), Efficacy and Safety of Laser-Assisted Combination Chemotherapy: An Explorative Imaging-Guided Treatment With 5-Fluorouracil and Cisplatin for Basal Cell Carcinoma. Lasers Surg Med, 53: 119-128. https://doi.org/10.1002/lsm.23323

3. Fuchs, C., Ortner, V., Hansen, F., Philipsen, P. and Haedersdal, M. (2021), Subclinical effects of adapalene-benzoyl peroxide: a prospective in vivo imaging study on acne micromorphology and transfollicular delivery. J Eur Acad Dermatol Venereol, 35: 1377-1385. https://doi.org/10.1111/jdv.17140

4. Banzhaf, C.A., Wind, B.S., Mogensen, M., Meesters, A.A., Paasch, U., Wolkerstorfer, A. and Haedersdal, M. (2016), Spatiotemporal closure of fractional laser-ablated channels imaged by optical coherence tomography and reflectance confocal microscopy. Lasers Surg. Med., 48: 157-165.https://doi.org/10.1002/lsm.22386

5. Ortner, V.K., Holmes, J., Haedersdal, M. and Philipsen, P.A. (2021), Morphometric Optical Imaging of Microporated Nail Tissue: An Investigation of Intermethod Agreement, Reliability, and Technical Limitations. Lasers Surg Med, 53: 838-848. https://doi.org/10.1002/lsm.23304

6. Corinna E. Psomadakis, Nadeem Marghoob, Brady Bleicher, Orit Markowitz, Optical coherence tomography, Clinics in Dermatology, 2021, ISSN 0738- 081X, https://doi.org/10.1016/j.clindermatol.2021.03.008

7. Wang-Evers, M., Casper, M.J., Glahn, J. et al. Assessing the impact of aging and blood pressure on dermal microvasculature by reactive hyperemia optical coherence tomography angiography. Sci Rep 11, 13411 (2021). https://doi.org/10.1038/s41598-021-92712-z

8. Mehrabi JN, Holmes J, Abrouk M, Wang JV, Pomerantz H, Palma AM, Zachary CB, Geronemus RG, Waibel JS, Kelly KM, Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography, Journal of the American Academy of Dermatology (2021), doi: https://doi.org/10.1016/j.jaad.2021.08.007.

9. Manfredini, M, Liberati, S, Ciardo, S, et al. Microscopic and functional changes observed with dynamic optical coherence tomography for severe refractory atopic dermatitis treated with dupilumab. Skin Res Technol. 2020; 26: 779– 787. https://doi.org/10.1111/srt.12868

10. Ciardo, S., Pezzini, C., Guida, S., Del Duca, E., Ungar, J., Guttman-Yassky, E., Manfredini, M., Farnetani, F., Longo, C. and Pellacani, G. (2021), A plea for standardization of confocal microscopy and optical coherence tomography parameters to evaluate physiological and para-physiological skin conditions in cosmetic science. Exp Dermatol, 30: 911- 922. https://doi.org/10.1111/exd.14359