Monday, August 19, 2019

Reflectance Confocal Microscopy- the latest Imaging Advancement for Dermatologists

FOREWORD by Dr. Robert Bard
The modern era of diagnostic clinical imaging continues to expand in areas of optimal speed, sensitivity and feasibility as part of its continued pursuits to bring a non-invasive diagnostic modalities to our treatment community.  The Reflectance Confocal Microscopy (RCM) gives dermatologists a major upgrade (over age-old microscopy) in their ability to assess pathologic and physiologic conditions of the skin with a higher level of clinical accuracy, greatly supporting the reduction of calls for biopsies of benign lesions.  Responding to the limitations of biopsies and conventional screening methods, the non-invasive movement which includes the 3D/4D Doppler Histogram,  Contrast Doppler Ultrasound, OCT (Optical Coherence Tomography) and the in vivo RCM brings a heightened level of performance and responsiveness in areas of resolution, magnification, depth, contrast, and immediate results from bedside.  

Dr. Manu Jain, Optical Imaging Specialist and Assistant Attending at Memorial Sloan Kettering Cancer Centre (MSK) Department of Dermatology provides great insight on the advantages of Reflectance Confocal Microscopy (RCM) for the diagnosis of skin cancers, in vivo—diagnosis at cellular level without cutting out the tissue at cellular level.

It offers several advantages over conventional light microscopy, including imaging of tissue in vivo and ability to provide bedside diagnosis. In addition to its applications in dermatology it can also be applied for oral cancers.  Meanwhile, we call this ‘optical biopsy’.   Microscopy is actually what's paving the way for digital imaging in dermatology. Before this it was the naked eye and magnifying lens.

As ultrasound is recognized for being non-invasive and radiation free, so is optical imaging – gathering epidermal and superficial dermal information through the use of LIGHT and laser.  It penetrates the skin to reach an estimated 200 microns in depth –often useful in dermatology to diagnose skin cancers like melanoma, basal cell carcinoma and squamous cell carcinoma. Because most tumors that appear originate at the dermo-epidermal junction (around a hundred-microns depth from skin surface). In addition to morphological and cellular information, RCM also provides information on the dynamic phenomenon of the blood flow very clearly.

Dr. Jain joined MSK four years ago and has led efforts to implement and use this technology at the bedside for skin cancer diagnostics.   There are limited expert readers of RCM in the United States, so to bridge this gap, Dr. Jain teaches and trains her residents in the dermatology and dermatopathology. She also teaches an annual CME accredited confocal course at MSK. She is also the Vice-president of recently formed American Confocal Group.

This innovation relies mainly on the reflectance (or back-scattering) of light from various tissue structures in the skin, non-invasively illuminating and magnifying images of planes or what are called “optical sections” in skin. “Structures in your skin are like tiny mirrors and when you shine focused light on the mirrors, whatever absorbs all the light appears dark and whatever reflects or back-scatters all the light appears bright”.

"I think it could be interesting to explore the option of combining confocal microscopy with ultrasound because ultrasound can give us the doppler information and also the depth is a very good with ultrasound… which we miss with confocal microscopy.  So that would be really great. Like they have done with confocal and optical coherence tomography."

 Her professional focus is to teach RCM to dermatologists and dermatopathologists.  For the large institutions, it’s fairly affordable and cost-effective as it takes only 15 minutes or 20 minutes to image and examine one lesion.  That means a patient gets scanned and diagnosed at the same time. This saves a lot of time for the patient at the end of the day because the patient doesn't have to wait for the biopsy report for week.

According to Dr. Jain's original bedside diagnosis study, RCM has shown remarkable sensitivity and specificity in hands of a novice.  For skin cancer, it is around 97% sensitivity and specificity in the range of 80%. "As an example, we’re examining a patient's new mole with confocal microscopy and if we are suspicious that it might be melanoma, we can use dermoscopy and confocal together to improve the accuracy of diagnosis.  Overall the sensitivity and specificity is 80-90% for diagnosis of skin cancer."

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IN VIVO CONFOCAL MICROSCOPY is fast becoming the new standard in dermal non-invasive imaging.  Originally conceptualized and developed at Massachusetts General Hospital (MGH), the technology offers better ways to detect skin cancers in real-time at the bedside while reducing the need for biopsies.  At the time, biopsy and pathology were the standard approach for detecting and diagnosing skin lesions.  The demand for advancing diagnostic imaging was a call from the 5 million+ new cases diagnosed in the US each year and another million cases detected in parts of Europe, UK, Australia, other regions of the world.

Dr. Milind Rajadhyaksha (Milind, as he prefers to be called) described how the RCM works in simplified terms: “We start with a bright light source, in our case it's a laser.  We focus the laser down to a very tiny spot inside the skin and we move the spot around in 2 dimensions, so we create a plane of illumination by moving that spot. Imagine having a flashlight which you point at a wall and now you move the flashlight back and forth, sideways and up and down until you can illuminate the entire wall.  Similarly, we ‘paint’ a single plane within tissue with a focused laser spot and we collect light from each location that the spot illuminates and that we can use that to produce an image. You can essentially create an image or a picture of a single layer of cells or single layer of tissue within skin.”

Milind states having built the original laboratory bench top microscope with his mentors, renowned physicist Dr. Robert Webb and dermatologist/laser pioneer Dr. Rox Anderson,in the early 1990s at MGH and later continued the development and translation of the technology at MSK since 2002. He has been involved with advancing both the IN vivo (directly on the patient) and the EX vivo microscope (any fresh tissue that has been removed from the patient, i.e. surgical excision or biopsy) to do faster imaging over large areas. Besides looking at skin cancers, this technology has been combined with a probe that can allow for imaging inside the oral cavity looking for oral cancers. “We've done a lot of work in imaging to guide treatment, surgeries and to guide laser ablations at MSK for more than a decade.”


DR. MANU JAIN is a research pathologist specializing in optical imaging techniques (i.e., in vivo/ex vivo microscopy), which are being explored in a research setting for non-invasive diagnosis of disease. She uses her in-depth knowledge of histopathology as well as my expertise in reading optical images to analyze and validate findings. Dr. Jain's career goal is to bring optical imaging from the bench to bedside, allowing for rapid real-time diagnosis that will improve clinical management and outcome for patients. Before joining MSK, Dr. Jain was a research pathologist in the departments of urology and surgical pathology at Weill Cornell Medical College, where she worked with other optical imaging techniques such as multiphoton microscopy and full-field optical coherence tomography. She has published many peer-reviewed articles in reputed journals and also co-authored two book chapters and presented my work at multiple national and international meetings.  For more information about Dr. Jain, visit: MSKCC.ORG

DR. MILIND RAJADHYAKSHA designs, develops and translates confocal microscopes for noninvasively guiding diagnosis and therapy of skin and oral/head-neck cancers. His work spans the entire spectrum from laboratory bench-top research through translational and clinical studies to clinical implementation, and he enjoys working in the so-called "valley of death" (and living through near-death experiences) between laboratory and clinic and between academia and industry. Two of his microscopes have been commercialized and are now being used in clinics. In January 2016, the US Centers for Medicare and Medicaid Services granted reimbursement codes for reflectance confocal microscopy of skin. Reflectance confocal microscopy is being routinely implemented to rule out malignancy and biopsy for skin lesions.  Meanwhile, fluorescence confocal microscopy is also being implemented for mapping of residual non-melanoma skin cancers in freshly excised tissue, to guide Mohs surgery.  For more information about Dr. Rajadhyaksha, visit: MSKCC.ORG


ROBERT L. BARD, MD, PC, DABR, FASLMS - Advanced Imaging & Diagnostic Specialist
Having paved the way for the study of various cancers both clinically and academically, Dr. Robert Bard co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- uses the latest in digital Imaging technology has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered Sonograms, Spectral Doppler, sonofluoroscopy, 3D/4D Image Reconstruction and the Spectral Doppler are safe, noninvasive, and does not use ionizing radiation. It is used as a complement to find anomalies and help diagnose the causes of pain, swelling and infection in the body’s internal organs while allowing the diagnostician the ability to zoom and ‘travel’ deep into the body for maximum exploration.

The New York Cancer Resource Alliance (NYCRA) is a volunteer-managed, self-funded Linkedin-based private group of cancer related professionals sponsored in part by the AngioFoundation (501c3) and ‘Awareness for a Cure’. NYCRA supports cancer survivors, patients, cancer organizations through education, advocacy and free access to resources and a network of caregivers dedicated to uniting an expanded community of colleages with similar common public interests. From medical doctors to survivors, book publishers to cancer coaches, fundraisers and advocates and the many other roles in between, our founders established this group to help unite this special community through the benefits of digital media and grow lasting relationships going forward.

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