UCLA’s Virtual Histology Could Eliminate Need for Invasive Biopsies for Some Skin Conditions and Cancers

Though the new technology could speed diagnoses of cancers and other skin diseases, it would also greatly reduce dermatopathology biopsy referrals and revenue

What effect would elimination of tissue biopsies have on dermatopathology and clinical laboratory revenue? Quite a lot. Dermatologists alone account for a significant portion of skin biopsies sent to dermatopathologists. Thus, any new technology that can “eliminate the need for invasive skin biopsies” would greatly reduce the number of histopathological referrals and reduce revenue to those practices.

Nevertheless, one such new technology may have been created by Ozcan Research Group in a proof-of-concept study they conducted at the University of California, Los Angeles (UCLA).

Called Virtual Histology, the technology applies artificial intelligence (AI) deep learning methods to reflectance confocal microscopy (RCM) images “to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue,” the UCLA scientists wrote in their study, published in the Nature peer-reviewed journal Light: Science and Applications.

Aydogan Ozcan, PhD

“What if we could entirely bypass the biopsy process and perform histology-quality staining without taking tissue and processing tissue in a noninvasive way? Can we create images that diagnosticians can benefit from?” asked Aydogan Ozcan, PhD (above), Chancellor’s Professor of Electrical and Computer Engineering at UCLA’s Samueli School of Engineering, one of the scientists who developed UCLA’s new virtual histology method, during an interview with Medical Device + Diagnostic Industry (MD+DI). (Photo copyright: Nature.)

Could Skin Biopsies be Eliminated?

The UCLA researchers believe their innovative deep learning-enabled imaging framework could possibly circumvent the need for skin biopsies to diagnose skin conditions.

“Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers.

“This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies,” the researchers added in their published study.

“This process bypasses several standard steps typically used for diagnosis, including skin biopsy, tissue fixation, processing, sectioning, and histochemical staining,” Aydogan Ozcan, PhD, Chancellor’s Professor of Electrical and Computer Engineering at UCLA’s Samueli School of Engineering, told Optics.org.

AI and Deep Learning in Dermatopathology

According to the published study, the UCLA team trained their neural network under an adversarial machine learning scheme to transform grayscale RCM images into virtually stained 3D microscopic images of normal skin, basal cell carcinoma, and pigmented melanocytic nevi. The new images displayed similar morphological features to those shown with the widely used hematoxylin and eosin (H&E) staining method.

“In our studies, the virtually stained images showed similar color contrast and spatial features found in traditionally stained microscopic images of biopsied tissue,” Ozcan told Photonics Media. “This approach may allow diagnosticians to see the overall histological features of intact skin without invasive skin biopsies or the time-consuming work of chemical processing and labeling of tissue.”

The framework covers different skin layers, including the epidermis, dermal-epidermis, and superficial dermis layers. It images deeper into tissue without being invasive and can be quickly performed.

“The virtual stain technology can be streamlined to be almost semi real time,” Ozcan told Medical Device + Diagnostic Industry (MD+DI). “You can have the virtual staining ready when the patient is wrapping up. Basically, it can be within a couple of minutes after you’re done with the entire imaging.”

Currently, medical professionals rely on invasive skin biopsies and histopathological evaluations to diagnose skin diseases and cancers. These diagnostic techniques can result in unnecessary biopsies, scarring, multiple patient visits and increased medical costs for patients, insurers, and the healthcare system.

Improving Time to Diagnosis through Digital Pathology

Another advantage of this virtual technology, the UCLA researchers claim, is that it can provide better images than traditional staining methods, which could improve the ability to diagnose pathological skin conditions and help alleviate human error.

“The majority of the time, small laboratories have a lot of problems with consistency because they don’t use the best equipment to cut, process, and stain tissue,” dermatopathologist Philip Scumpia, MD, PhD, Assistant Professor of Dermatology and Dermatopathology at UCLA Health and one of the authors of the research paper, told MD+DI.

“What ends up happening is we get tissue on a histology slide that’s basically unevenly stained, unevenly put on the microscope, and it gets distorted,” he added, noting that this makes it very hard to make a diagnosis.  

Scumpia also added that this new technology would allow digital images to be sent directly to the pathologist, which could reduce processing and laboratory times.

“With electronic medical records now and the ability to do digital photography and digital mole mapping, where you can obtain a whole-body imaging of patients, you could imagine you can also use one of these reflectance confocal devices. And you can take that image from there, add it to the EMR with the virtual histology stain, which will make the images more useful,” Scumpia said. “So now, you can track lesions as they develop.

“What’s really exciting too, is that there’s the potential to combine it with other artificial intelligence, other machine learning techniques that can give more information,” Scumpia added. “Using the reflectance confocal microscope, a clinician who might not be as familiar in dermatopathology could take images and send [them] to a practitioner who could give a more expert diagnosis.”

Faster Diagnoses but Reduced Revenue for Dermatopathologists, Clinical Labs

Ozcan noted that there’s still a lot of work to be done in the clinical assessment, validation, and blind testing of their AI-based staining method. But he hopes the technology can be propelled into a useful tool for clinicians.

“I think this is a proof-of-concept work, and we’re very excited to make it move forward with further advances in technology, in the ways that we acquire 3D information [and] train our neural networks for better and faster virtual staining output,” he told MD+DI.

Though this new technology may reduce the need for invasive biopsies and expedite the diagnosis of skin conditions and cancers—thus improving patient outcomes—what affect might it have on dermatopathology practices?

More research and clinical studies are needed before this new technology becomes part of the diagnosis and treatment processes for skin conditions. Nevertheless, should virtual histology become popular and viable, it could greatly impact the amount of skin biopsy referrals to pathologists, dermatopathologists, and clinical laboratories, thus diminishing a great portion of their revenue. 

—JP Schlingman

Related Information:

Virtual Histology Eliminates Need for Invasive Skin Biopsies

UCLA Deep-learning Reduces Need for Invasive Biopsies

AI Imaging Method Provides Biopsy-free Skin Diagnosis

Light People: Professor Aydogan Ozcan

Histology Process Bypasses Need for Biopsies, Enables Diagnoses

Reflection-Mode Virtual Histology Using Photoacoustic Remote Sensing Microscopy

Introduction to Reflectance Confocal Microscopy and Its Use in Clinical Practice

Biopsy-free In Vivo Virtual Histology of Skin Using Deep Learning

Can This New Tech Reduce the Need for Skin Biopsies?

Lithuanian Researchers Develop Novel Noninvasive Method for Diagnosing Melanoma That Has Greater than 90% Accuracy

Computer-aided diagnostic system combines optical dermatoscopy, spectrophotometry and high-frequency ultrasound imaging techniques to differentiate malignant lesions from benign moles

Detecting skin cancer via the use of skin biopsies is the bread and butter of many dermatopathology practices. But new technologies that can instantly detect and distinguish different types of skin malignancies may result in a reduced flow of skin biopsies to dermatopathologists in the not-too-distant future.

This may happen because a team of researchers from two universities in Lithuania (Kaunas University of Technology and Lithuanian University of Health Sciences) has developed a patented computer-aided diagnostic (CADx) system capable of differentiating melanoma from a benign nevus [mole] with accuracy greater than 90%, their study of 100 patients showed.

In, “Diagnostics of Melanocytic Skin Tumours by a Combination of Ultrasonic, Dermatoscopic, and Spectrophotometric Image Parameters,” published in Diagnostics, a peer-reviewed, open-access MDPI journal, the scientists noted that their hybrid method combines the three most promising noninvasive quantitative imaging techniques in use for diagnosing melanomas:

The new technique achieved a more accurate method of differentiating melanoma from benign lesions, according to the researchers.

“The novelty of our method is that it combines diagnostic information obtained from different non-invasive imaging technologies such as optical spectrophotometry and [high-frequency] ultrasound. Based on the results of our research, we can confirm that the developed automated system can complement the non-invasive diagnostic methods currently applied in the medical practice by efficiently differentiating melanoma from a melanocytic mole,” said Renaldas Raišutis, PhD, coauthor of the study, in a KTU news release.

Graph of skin cancer rates by state

According to the Skin Cancer Foundation, one in five Americans will develop skin cancer by the age of 70 and more than two people in the United States die of skin cancer every hour. Early diagnosis is vital. If a malignant melanoma—the most lethal type of skin cancer—is found early, the five-year survival rate is 99%. (Graphic copyright: Healthline.)

“An efficient diagnosis of an early-stage malignant skin tumor could save critical time, more patients could be examined, and more of them could be saved,” Raišutis said in the news release. He added that the CADx-based diagnostic system is aimed at medical professionals but at a price that makes it affordable for smaller medical institutions. The Lithuanian team also is working to design a system that could be marketed for home use.

New Non-invasive Optical Technology May Reduce Demand for Skin Biopsies

A systematic review article published in Frontiers in Medicine Dermatology compared current diagnostic techniques for melanoma. It noted, “The current gold standard for melanoma diagnosis is the administration of dermoscopy, followed by a biopsy and subsequent histopathological analysis of the excised tissue. To minimize the risk of misdiagnosis of true melanomas, a significant number of dermoscopically ambiguous lesions are biopsied [increasing] the overall diagnostic costs and time to obtain the final diagnosis.”

But continuing technological innovations may be setting the stage for a reduction in the number of skin biopsies performed each year. In addition to the novel diagnostic method announced by the Lithuanian researchers, an Israeli scientist has created an innovative optical technology that can instantly and non-invasively detect and distinguish between three primary skin cancers:

Abraham Katzir, PhD, a physics professor at Tel Aviv University, has developed a fiber-optic evanescent wave spectroscopy (FEWS) system based on middle infrared transmitting AgCIBr fibers and a Fourier-transform infrared spectrometer that determines the properties of the various skin lesions and identifies them based on their coloration within the infrared spectrum.

Abraham Katzir, PhD and patient

Tel Aviv University Physics Professor Abraham Katzir, PhD (above), demonstrates his new method of detecting cancerous skin lesion, which employs infrared sensors and optical fibers to determine the properties of various lesions on the skin and identify them based on their coloration within the infrared spectrum. (Photo copyright: Tel Aviv University.)

“We figured that with the help of devices that can identify these colors, healthy skin and each of the benign and malignant lesions would have different ‘colors,’ which would enable us to identify melanoma,” Katzir said in an Israel 21c news article.

The Israeli researchers published their study of 100 patients at a major Israeli hospital in Medical Physics, a journal of the American Association of Physicists in Medicine (AAPM).

“Melanoma is a life-threatening cancer, so it is very important to diagnose it early on, when it is still superficial,” Katzir told Israel 21c, adding that the new technology has the potential to cause “dramatic change” in the field of diagnosing and treating skin cancer, “and perhaps other types of cancer as well.”

As advancements in the non-invasive diagnosis of skin cancers continue, dermatopathologists—and in fact all anatomic and histopathology practices—should prepare for the financial impact this change may have on their clinical practices as demand for skin biopsies decreases.

Andrea Downing Peck

Related Information

Novel Method Develop by Lithuanian Scientists Can Reach More than 90% Accuracy in Detecting Melanoma

Diagnostics of Melanocytic Skin Tumours by a Combination of Ultrasonic, Dermatoscopic and Spectrophotometric Image Parameters

Scientist Develops Instant Non-Invasive Cancer Detection Technology

Technical Note: Non-Invasive Mid-IR Fiber-Optic Evanescent Wave Spectroscopy (FEWS) For Early Detection of Skin Cancers

Comparative Analysis of Diagnostic Techniques for Melanoma Detection: A Systematic Review of Diagnostic Test Accuracy Studies and Meta-Analysis

University of Texas Researchers Reveal a Portable Cancer Detection Device with the Potential to Significantly Reduce the Number of Skin Biopsies Sent to Dermatopathologists

Team of bioengineers succeeds in putting three different imaging technologies into a handheld probe that could be used by physicians to assess skin lesions in their offices

Dermatopathologists and pathology practice administrators will be keenly interested in a new, hand-held diagnostic device that is designed to reduce the need for skin biopsies. Because of high volume of skin biopsies referred to pathologists, any significant reduction in the number of such case referrals would have negative revenue impact on medical laboratories  that process and diagnose these specimens.

This innovative work was done at the University of Texas at Austin’s Cockrell School of Engineering. The research team developed a probe that uses three different light modalities to detect melanoma and other skin cancer lesions in real-time, according to a news release.

“Do It Yourself” Dermatopathology Will Use Consumer’s Cell Phone Images

Company intends to use pattern recognition software to evaluate risk of skin cancer

A “do it yourself” dermatopathology service for consumers is coming soon, according to Health Discovery Corporation (HDC) of Savannah, Georgia. The company is preparing to introduce a cell phone-based tool to help consumers recognize whether a mole or other skin lesion needs examination by a dermatologist.

Using their cell phone cameras, consumers would click a photo of the skin lesion, then forward that image to a computer at HDC. Using pattern recognition algorithms developed by the company, called Support Vector Machines, the computer would analyze the image. A report telling the consumer whether the lesion was low, medium or high risk for skin cancer would be sent as a text message. This text message would include a list of dermatologists located near the consumer. The list of dermatologist referrals would be targeted to the user’s geographic area. HPC would compile this list, based on GPS data collected from the cell phone transmission.


Meet the Virtual Dermatopathology Lab, Doing Global Business From Boston

Second opinion dermpath business combines digital pathology, glass slides, and the Internet.

Telepathology, Federal Express, and internet technologies are the cornerstones of a flourishing second opinion business by dermatopathologists in Boston, Massachusetts. In just a few years, the practice has built a national and international clientele. This confirms that there is already overseas demand for access to expert pathologists with subspecialty skills.

Another unique twist to this pathology second opinion business is its use of a subscription arrangement. Referring pathology groups can pay sliding flat fee per case, based on a pre-agreed monthly volume. This arrangement has proved popular.