BioReference Labs Goes Live With Digital Pathology Plus AI

BioReference Labs Goes Live With Digital Pathology Plus AI

BioReference Labs Goes Live With Digital Pathology Plus AI

OPKO’s BioReference Labs (Elmwood Park, NJ) went live in December with new whole-slide imaging scanners from Leica Biosciences (Buffalo Grove, IL). The scanners have been integrated with a digital pathology solution, PathFlow, made by Gestalt Diagnostics (Spokane, WA). PathFlow is a cloud-based software system that has helped integrate BioReference’s LIS, workflow and scanned slide images with artificial intelligence algorithms developed by MindPeak (Hamburg, Germany). BioReference is also using PathFlow for slide image management and archival storage.

BioReference is using MindPeak’s AI tool (named BreastIHC) to detect and quantify breast cancer cells from digitized slide images with immunohistochemistry at its main laboratory in northern New Jersey. Pathologists can access their case and slide images securely on their computer monitors and use their mouse to outline regions of interest (ROI). All cells within this outlined ROI are instantly classified into positively stained tumor and unstained tumor cells. The panel of algorithms include five key tumor markers (ER, PR, Ki-67, HER2, and P53) which can be counted and scored.

Eventually, Dan Roark, Chief Executive Officer, Gestalt Diagnostics, expects the AI algorithms to both automatically identify the regions of interest in addition to performing IHC marker positivity scoring.

Digital Pathology & AI Market Growth
Separately, Roark says that after more than 10 years of limited adoption, digital pathology is finally starting to take off in the clinical market in the United States. Whole slide scanners have gotten quicker and less expensive. For example, it used to take 8-10 minutes to scan a slide but now takes as little as 30 seconds. But the biggest driver is the pathologist efficiency gains obtained when AI is applied to digitized slides. “The number of RFP requests we receive is exploding,” says Roark.

Worldwide Opportunities for U.S.-Based Pathologists
The U.S. has more working pathologists per capita than most other countries. For example, there are approximately 20,000 actively practicing pathologists in the United States, according to the American Medical Association. This works out to a ratio of one pathologist for every 17,000 people.

Ibex To Focus On U.S. Market For AI-Assisted Pathology

Ibex To Focus On U.S. Market For AI-Assisted Pathology

Ibex To Focus On U.S. Market For AI-Assisted Pathology

Ibex Medical Analytics (Tel Aviv, Israel and Boston, MA) has hired Douglas Clark, MD, as its Chief Medical Officer, Americas. Ibex also announced that Joseph Mossel, its co-founder and CEO, is relocating to the United States to lead the company’s expansion in North America from its Boston headquarters.

Prior to joining Ibex, Clark was Chief Medical Officer at TriCore Reference Labs (Albuquerque, NM), where he led the transition to digital pathology. Before that, Clark was Chair of the Department of Pathology at the University of New Mexico School of Medicine and was previously Professor of Pathology and Oncology at The Johns Hopkins Medical Institutions.

Ibex develops AI algorithms and digital workflows that help detect and grade cancer in biopsies. The company’s AI-powered Galen algorithm is currently being used by CorePlus Services in Puerto Rico (see LE, September 2020) and Alverno Clinical Labs in Indiana (see LE, August 2021).

Earlier this year, Ibex’s Galen platform was granted Breakthrough Device Designation by the FDA, which will help fast-track clinical review and regulatory approval.

Ibex raised $38 million from a Series B financing private equity round in March. Lead investors included Octopus Ventures and 83North, with additional participation from aMoon, Planven Entrepreneur Ventures and Dell Technologies Capital, the corporate venture arm of Dell Technologies. Ibex has now raised a total of $52 million since its inception in 2016.

Spotlight Interview With Paige CEO Leo Grady

Spotlight Interview With Paige CEO Leo Grady

Spotlight Interview With Paige CEO Leo Grady

Paige (New York, NY) was founded by pathologists and scientists from Memorial Sloan Kettering Cancer Center in 2017. Paige develops artificial 
intelligence (AI)-based systems that help diagnose cancer. In early 2019, the
company hired Leo Grady, PhD, as Chief Executive Officer and Board member. He had previously been Senior Vice President of Engineering at  HeartFlow (Redwood City, CA), where he led development efforts for  HeartFlow’s 3D modeling software for coronary artery disease. He received a  B.S. degree in Electrical Engineering at the University of Vermont and a PhD in Cognitive and Neural Systems from Boston University. Below is a summary of Laboratory Economics’ interview with Dr. Grady in late June.

Who founded Paige?
The intellectual property related to the AI-based computational pathology used by Paige was initially developed by Thomas Fuchs, PhD, while he was Director of Computational Pathology at The Warren Alpert Center for Digital and Computational Pathology at Memorial Sloan Kettering (MSK). Fuchs co-founded Paige with David Klimstra, MD, Chairman of the Department of Pathology at MSK, in 2017. Fuchs is Chief Scientific Officer at Paige. Klimstra will become our Chief Medical Officer effective August 1.
Paige currently has more than 100 employees, mostly in the United States, with a small, but growing, presence in the United Kingdom and Europe.

Where did Paige get the annotated pathology slides needed to develop its AI algorithms?
As part of spin-out from MSK, Paige signed a comprehensive license agreement, giving it exclusive access to the hospital’s archive of 25 million annotated pathology slides and its intellectual property in computational pathology. To date, Paige has digitized more than five million slides from the MSK archive.

How much capital has Paige raised?
We’ve raised a total of $220 million to date, including $125 million raised in January from a series C financing led by Casdin Capital, Johnson & Johnson Innovation (JJDC) and KKR. Paige’s largest shareholders also include MSK, Breyer Capital, Goldman Sachs and Healthcare Venture Partners.

Where do Paige’s software programs stand with the FDA?
In early 2019, Paige received an FDA breakthrough designation for its software program for the automated detection of cancer in prostate biopsies. FDA clearance is expected to start with prostate cancer and then expand to additional cancers. In addition, in December 2020, the company obtained two CE marks for software aimed at breast and prostate cancers, including the ability to rate tumor samples, deliver a prognosis and guide treatment planning. Finally, Paige’s digital pathology image viewer, FullFocus, received FDA clearance in July 2020. The clearance allows for use of FullFocus with the FDA-authorized Philips Ultra Fast Scanner and paves the way for use with additional scanners in the future.

How accurate are Paige’s AI-based software programs?
A study recently published in the Journal of Pathology showed that Paige Prostate had 100% sensitivity and 100% negative predictive value (NPV) at the patient level when analyzing 661 prostate needle biopsy slides from 100 consecutive patients in a real-world setting.

The study took place at Grupo Oncoclinicas (São Paulo, Brazil), which is the largest private provider of cancer care in Latin America and was the first institution in the world to fully deploy Paige digital and computational pathology products for routine use. (See Independent Real-World Application of a Clinical-Grade Automated Prostate Cancer Detection System, Journal of Pathology, June 2021.)

How about pathologist productivity gains?
For the Grupo Oncoclinicas study, Paige Prostate generated binary predictions, benign or suspicious for cancer. A benign prediction prompted no further action by a pathologist, whereas a classification of suspicious would prompt pathologist review and/or additional IHC to confirm the presence of a malignancy. Given its high sensitivity and NPV, and specificity
of 0.78, Paige Prostate showed the potential to be used as a screening tool that flags suspicious slides needing pathologist review. Given that roughly 80% of prostate biopsy slides are negative, screening with AI could provide huge gains in pathologist productivity. Ultimately, the medical community will decide how best to use AI.

Won’t digitizing slides and performing AI analysis disrupt workflow and slow turnaround?
The Grupo Oncoclinicas study showed that Paige Prostate could improve efficiency by an estimated 65.5%. The use of AI allowed the pathologists to focus their microscope time on those slides most likely to contain cancer. It can also save time by identifying specimen samples requiring recuts and/or additional staining prior to being viewed by a pathologist.

Will AI products like Paige Prostate speed the transition to digital pathology?
The adoption of digital pathology to date has moved very slowly. We estimate that only 5% of pathology slides in the U.S. are currently being digitized. Return on investment (ROI) has been the biggest obstacle. The transition to digital pathology requires significant investment in terms
of capital expense, workflow changes, floor space, and image storage. Without added reimbursement, it’s hard to make a business case for digitizing slides. However, AI-based tools that raise pathologist productivity provide an ROI for going digital.

Why is Europe ahead of the United States in terms of digital pathology adoption?
The regulatory process for digital pathology in Europe was quicker and there is a greater shortage of pathologists. Even so, the majority of pathology cases in Europe are still interpreted using traditional light microscopes.

Paige recently announced some contracts with big commercial pathology labs.
Yes. Under our new agreement with Quest Diagnostics, Paige’s proprietary AI tools will analyze digitized slides from Quest and its AmeriPath and Dermpath businesses to develop new software products for diagnosing cancer and other diseases. The collaboration will initially focus on solid tumor cancers, such as prostate, breast, colorectal and lung. Assuming regulatory clearance, Quest plans to use approved software products in its pathology operations.

In the near term, the collaboration also intends to license the insights to biopharmaceutical and research organizations to aid biomarker discovery, drug research and development and companion diagnostics.

Separately, Inform Diagnostics (Irving, TX) has agreed to immediately start using Paige’s FullFocus digital pathology viewer as well as our data management system for storing digital pathology slides.

How will the role of pathologists evolve over the next 5-10 years?
I expect there’ll be less microscopy-based work in a more distributed model. But the role and visibility of pathologists may get elevated due to digital pathology and AI. Digital pathology images allow pathologists to communicate more visually with ordering physicians, while AI will increase their diagnostic accuracy thereby providing more value to physicians and patients.

CorePlus Details Its Use Of Artificial Intelligence For Prostate Cancer

CorePlus Details Its Use Of Artificial Intelligence For Prostate Cancer

CorePlus Details Its Use Of Artificial Intelligence For Prostate Cancer

Last month, LE briefly noted that CorePlus Servicios Clínicos y Patológicos LLC (Carolina, Puerto Rico) had become the first independent lab in the Americas to begin using artificialintelligence-assisted (AI) pathology for prostate cancer diagnostics. This month wegot in touch with CorePlus President Mariano de Socarraz to find out more.

Can you describe CorePlus?
We opened our CLIA-certified laboratory in Carolina, Puerto Rico in 2008. We currently have 115 employees, including four pathologists. CorePlus is full-service independent laboratory. Among our specializations is uropathology. We process approximately 3,000 prostate cancer cases (~36,000 slides) per year, representing more than half of all outpatient prostate cancer biopsies performed in Puerto Rico.

Is operating a lab in Puerto Rico different than in mainland United States?
No. Puerto Rico is a U.S. territory that must follow all federal lab regulations, including CLIA. Medicare and Medicaid insurance cover the majority of the 3.2 million people living in Puerto Rico and the biggest private insurer is Triple-S, which is an independent licensee of the Blue Cross Blue Shield Association. The biggest difference is probably reimbursement rates, which are substantially lower in Puerto Rico.

Among the competing clinical labs in Puerto Rico are Laboratorio Clinico Toledo and Laboratorios Borinquen. Anatomic pathology labs include Hato Rey Pathology and Puerto Rico Pathology. Quest Diagnostics has had a reduced presence following the damage to its lab facilities from Hurricane Maria in 2017. LabCorp transports specimens to its labs in Florida.

When did CorePlus transition to digital pathology?
We began digitizing slides using 3DHISTECH scanners in mid-2019. By late 2019 we had completed validation and by early 2020 our pathologists were reading digitized images for all our pathology cases, including all routine histopathology and stains.

What type of computer screens do your pathologists read the digital slide images from?
CorePlus validated the Dell UltraSharp 49 Curved Monitor – U4919DW. It’s a high-end, business grade monitor with a Delta E of <2 (color difference perception) and an aspect ratio of 32:9:0. This aspect ratio is the equivalent of two 27-inch monitors running at 2K.

And how did you get involved with AI-assisted pathology?
In August 2018, I read about a validation study conducted by University of Pittsburgh Medical Center which used an AI-based algorithm to detect and characterize prostate cancer from digitized slides. This study [recently published in The Lancet Digital Health] showed that an AI-based algorithm demonstrated 98% sensitivity and 97% specificity at detecting prostate cancer from 1,600 different tissue slide images that had been collected from 100 patients seen at UPMC who were suspected of having prostate cancer. It even spotted six potentially malignant slides that expert pathologists had failed to identify initially. This interested me, so I contacted the company that developed the algorithm, Israel-based Ibex Medical Analytics. We ran our own validation studies on 1,301 digitized prostate tissue slides and found results similar to those at UPMC. Overall accuracy was 99.4% with 96.9% specificity and 96.5% sensitivity.

How have you integrated AI into your pathology lab?
Our pathologists continue to read digitized images for every prostate tissue slide prepared by our lab. But starting in June, we also began sending digitized images of each slide to the Ibex cloud. Ibex runs its AI-based algorithm on each slide which provides 100% quality control on all prostate cases. This serves as a digital second opinion for our pathologists.

What happens when there is a discrepancy between the pathologist’s exam and the algorithm?

The pathologist goes back and reviews the slide(s) and/or orders an immunohistochemistry. I believe that we have reduced the potential for a misdiagnosis on prostate cancer biopsies to much less than 1%. This is significant given that even an expert uropathologist can miss 3%. So the AI
algorithm is acting as a failsafe that is catching cases that might otherwise be missed.

Was there any reluctance from your pathologists as you transitioned to digital pathology and AI for prostate?
The pathologists were always fully engaged in the transition. Our pathologists say they would never go back to the microscope, especially given their ability to read digitized slides at home during the pandemic. We have analyzed over 1,000 prostate biopsy cases using digital pathology with AI assistance to date. In real world practice it has helped identify lesions that would otherwise have been missed.

Will you apply AI-based algorithms to other cancers?
Yes, we are planning to start using an Ibex algorithm for second reads on all breast cancer cases within the next few weeks.

How does your lab get compensated for using digital pathology and AI to improve accuracy?
We do not get additional compensation and that is the problem with the current CPT-based feefor-service reimbursement model. AI increases accuracy and reduces utilization of immunohistochemistry and there ought to be some coding mechanism that fairly compensates labs that use it.
In the meantime, the increased efficiency that the combination of digital pathology and AI provides has helped offset the initial technology investment and development cost. In addition, the increased accuracy at CorePlus through its use of AI should lead to more clients. Knowing that 100% of prostate cancer cases sent to CorePlus are getting an AI second opinion should raise urologists’ confidence in our lab.

How will AI affect the practice of pathology over the long term?
After our current use of digital pathology and AI as a second read tool, I anticipate it will progress to be used as a triage tool and finally for primary reads with the supervision of a pathologist. The role of pathologists will evolve away from time at the traditional microscope toward selecting the
right AI algorithm to apply to a digitized slide and reviewing results in combination with a patient’s medical record to form a diagnosis.

Switching gears, is CorePlus performing Covid-19 PCR testing?
We started Covid-19 PCR testing on the Roche cobas 6800 platform in late April. CorePlus has been on an allocation of seven kits per week (equal to 1,344 tests). To compensate for the test reagent shortage, we began pooled testing for three specimens at a time in July. This has expanded our capacity to about 4,000 tests per week and we are preparing to increase our pool size to six specimens, which will double our capacity to 8,000 tests per week.

How do you see the Covid-19 pandemic ending?
It is not going away any time soon, even with a vaccine. Population immunity may take years.