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Samsung Medical Center Combines 5G with Digital Pathology to Speed Anatomic Pathologist’s Readings of Frozen Sections, Cuts Test TAT in Half

HIMSS names SMC a ‘world leader’ in digital pathology and awards the South Korean Healthcare provider Stage 7 DIAM status  

Anatomic pathologists and clinical laboratory managers in hospitals know that during surgery, time is of the essence. While the patient is still on the surgical table, biopsies must be sent to the lab to be frozen and sectioned before going to the surgical pathologist for reading. Thus, shortening time to answer for frozen sections is a significant benefit.

To address an overwhelming number of frozen section tests and delays in surgical pathology turnaround times (TATs), Samsung Medical Center (SMC) in Seoul, South Korea, used 5G network connectivity to develop an integrated digital pathology system that is “enhancing the speed of clinical decision-making across its facilities,” according to Healthcare IT News

This effort in surgical pathology is part of a larger story of the digital transformation underway across all service lines at this hospital. For years, SMC has been on track to become one of the world’s “intelligent hospitals,” and it is succeeding. In February, SMC became the first healthcare provider to achieve Stage 7 in the HIMSS Digital Imaging Adoption Model (DIAM), which “assesses an organization’s capabilities in the delivery of medical imaging,” Healthcare IT News reported.

As pathologists and clinical laboratory leaders know, implementation of digital pathology is no easy feat. So, it’s noteworthy that SMC has brought together disparate technologies to reduce turnaround times, and that the medical center has caught the eye of leading health information technology (HIT) organizations. 

Kee Taek Jang, MD

“The digital pathology system established by the pathology department and SMC’s information strategy team could be one of the good examples of the fourth industrial revolution model applied to a hospital system,” anatomic pathologist Kee Taek Jang, MD (above), Professor of Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center told Healthcare IT News. Clinical laboratory leaders and surgical pathologists understand the value digital pathology can bring to faster turnaround times. (Photo copyright: Samsung Medical Center.)

Anatomic Pathologists Can Read Frozen Sections on Their Smartphones

Prior to implementation of its 5G digital pathology system, surgeons and their patients waited as much as 20 minutes for anatomic pathologists to traverse SMC’s medical campus to reach the healthcare provider’s cancer center diagnostic reading room, Healthcare IT News reported.

Now, SMC’s integrated digital pathology system—which combines slide scanners, analysis software, and desktop computers with a 5G network—has enabled a “rapid imaging search across the hospital,” Healthcare IT News noted. Surgical pathologists can analyze tissue samples faster and from remote locations on digital devices that are convenient to them at the time, a significant benefit to patient care.

“The system has been effective in reducing the turnaround time as pathologists can now attend to frozen test consultations on their smartphone or tablet device via 5G network anywhere in the hospital,” Jean-Hyoung Lee, SMC’s Manager of IT Infrastructure, told Healthcare IT News which noted these system results:

Additionally, through the 5G network, pathologists can efficiently access CT scans and MRI data on proton therapy cancer treatments. Prior to the change, the doctors had to download the image files in SMC’s Proton Therapy Center, according to a news release from KT Corporation, a South Korean telecommunications company that began working with SMC on building the 5G-connected digital pathology system in 2019.

SMC Leads in Digital Pathology: HIMSS

Earlier this year, HIMSS named SMC a “world leader” in digital pathology and first to reach Stage 7 in the Digital Imaging Adoption Model (DIAM), Healthcare IT News reported.

DIAM is an approach for gauging an organization’s medical imaging delivery capabilities. To achieve Stage 7—External Image Exchange and Patient Engagement—healthcare providers must also have achieved all capabilities outlined in Stages 5 and 6.

In addition, the following must also have been adopted:

  • The majority of image-producing service areas are exchanging and/or sharing images and reports and/or clinical notes based on recognized standards with care organizations of all types, including local, regional, or national health information exchanges.
  • The application(s) used in image-producing service areas support multidisciplinary interactive collaboration.
  • Patients can make appointments, and access reports, images, and educational content specific to their individual situation online.
  • Patients are able to electronically upload, download, and share their images.

“This is the most comprehensive use of integrated digital pathology we have seen,” Andrew Pearce, HIMSS VP Analytics and Global Advisory Lead, told Healthcare IT News.

SMC’s Manager of IT Planning Seungho Lim told Healthcare IT News the medical center’s goal is to become “a global advanced intelligent hospital through digital health innovation.” The plan is to offer, he added, “super-gap digital services that prioritize non-contact communication and cutting-edge technology.”

For pathologists and clinical laboratory leaders, SMC’s commitment to 5G to move digital pathology data is compelling. And its recognition by HIMSS could inspire more healthcare organization to make changes in medical laboratory workflows. SMC, and perhaps other South Korean healthcare providers, will likely continue to draw attention for their healthcare IT achievements.   

Donna Marie Pocius

Related Information:

Using 5G to Cut Down Diagnostic Reading by Half

KT and Samsung Medical Center to Build 5G Smart Hospital

Samsung Medical Center Achieves Stage 7 DIAM and EMRAM

Finding the Future of Care Provision: the Role of Smart Hospitals

K-Hospital Fair 2022, Success in Digital Transformation (DX) Introducing “Smart Logistics”

Digital Health Market to Hit $809.2 Billion by 2030: Grand View Research, Inc.

South Korea: The Perfect Environment for Digital Health

Two University of North Carolina School of Medicine Laboratories Develop Technique for Seeing How Proteins Change Shape In Vivo

UNC’s novel way to visualize the human proteome could lead to improved clinical laboratory tests along with the development of new therapies

Diagnostic testing based on proteomics is considered to be a field with immense potential in diagnostics and therapeutics. News of a research breakthrough into how scientists can visualize protein activity within cells will be of major interest to the pathologists, PhDs, and medical laboratory scientists who specialize in clinical laboratory testing involving proteins.

Proteins are essential to all life and to the growth, maintenance, and repair of the human body. So, a thorough understanding of how they function within living cells would be essential to informed medical decision-making as well. And yet, how proteins go about doing their work is not well understood.

That may soon change. Scientists at the University of North Carolina (UNC) School of Medicine have developed an imaging method that could provide new insights into how proteins alter their shapes within living cells. And those insights may lead to the development of new therapies and medical treatments.

Dubbed “binder-tag” by the UNC scientists, their new technique “allows researchers to pinpoint and track proteins that are in a desired shape or ‘conformation,’ and to do so in real time inside living cells,” according to a UNC Health news release.

Two labs in the UNC School of Medicine’s Department of Pharmacology collaborated to develop the binder-tag technique:

The scientists published their findings in the journal Cell, titled, “Biosensors Based on Peptide Exposure Show Single Molecule Conformations in Live Cells.”

Klaus Hahn PhD
 
“No one has been able to develop a method that can do, in such a generalizable way, what this method does. So, I think it could have a very big impact,” said lead author of the UNC study Klaus Hahn PhD (above), in the news release. “With this method we can see, for example, how microenvironmental differences across a cell affect, often profoundly, what a protein is doing,” he added. This research may enlarge scientists’ understanding of how the human proteome works and could lead to new medical laboratory tests and therapeutic drugs. (Photo copyright: UNC School of Medicine.)
 

How Binder-Tag Works

During their study, the UNC scientists developed binder-tag “movies” that allow viewers to see how the binder-tag technique enables the tracking of active molecules in living cells.

According to Cosmos:

  • The technique involves two parts: a fluorescent binder and a molecular tag that is attached to the proteins of interest.
  • When inactive, the tag is hidden inside the protein, but when the protein is ready for action it changes shape and exposes the tag.
  • The binder then joins with the exposed tag and fluoresces. This new fluorescence can easily be tracked within the cell.
  • Nothing else in the cell can bind to the binder or tag, so they only light up when in contact on the active protein.
  • This type of visualization will help researchers understand the dynamics of a protein in a cell.

“The method is compatible with a wide range of beacons, including much more efficient ones than the interacting beacon pairs required for ordinary FRET [fluorescence resonance energy transfer]. Binder-tag can even be used to build FRET sensors more easily. Moreover, the binder-tag molecules were chosen so that nothing in cells can react with them and interfere with their imaging role,” Hahn said in the news release.

“Only upon exposure can the peptide specifically interact with a reporter protein (the binder). Thus, simple fluorescence localization reflects protein conformation. Through direct excitation of bright dyes, the trajectory and conformation of individual proteins can be followed,” the UNC researchers wrote in Cell. “The simplicity of binder-tag can provide access to diverse proteins.”  

The UNC researchers’ binder-tag technique is a way to overcome the dire challenge of seeing tiny and hard-working proteins, Cosmos noted. Typical light microscopy does not enable a view of molecules at work. This paves the way for the new binder-tag technique, UNC pointed out.

“With this method, we can see, for example, how microenvironmental differences across a cell affect—and often profoundly—what a protein is doing,” Hahn said. “For a lot of protein-related diseases, scientists haven’t been able to understand why proteins start to do the wrong thing. The tools for obtaining that understanding just haven’t been available.”

More Proteins to Study

More research is needed before the binder-tag method can be used in diagnostics. Meanwhile, the UNC scientists intend to show how binder-tag can be applied to other protein structures and functions. 

“The human proteome has between 80,000 and 400,000 proteins, but not all at one time. They are expressed by 20,000 to 25,000 human genes. So, the human proteome has great promise for use in diagnostics, understanding disease, and developing therapies,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.

Medical scientists and diagnostics professionals will want to stay tuned to discover more about the tiny—though mighty—protein’s contributions to understanding diseases and patient treatment.     

Donna Marie Pocius

Related Information:

Biosensors Based on Peptide Exposure Show Single Molecule Conformations in Live Cells

Powerful Technique Allows Scientists to Study How Proteins Change Shape Inside Cells

Watching Proteins Dance

Binder-Tag: A Versatile Approach to Probe and Control the Conformational Changes of Individual Molecules in Living Cells

UC Davis Researchers Develop Microscope That Uses Ultraviolet Light for Diagnosis, Eliminates Need for Traditional Histology Slide Preparation

MUSE microscope speeds up some anatomic pathology laboratory processes and removes exposure to toxic fixative chemicals

Because they handle tissue specimens, histotechnologists, anatomic pathologists, and hospital nurses are exposed to deadly chemicals such as formaldehyde, formalin, Xylene, and Toluene. The risks associated with these chemicals has been covered regularly by Dark Daily as recently as 2018 and as far back as 2011. (See, “Europe Implements New Anatomic Pathology Guidelines to Reduce Nurse Exposure to Formaldehyde and Other Toxic Histology Chemicals,” January 3, 2018; and, “Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene,” July 5, 2011.)

Now, scientists at the University of California at Davis (UC Davis) have developed a microscope that uses ultraviolet light (UV) to illuminate tissue samples. The UV microscope removes the need for traditional histology processes involved with preparation of tissue to produce conventional slides and makes it possible for anatomic pathologists to evaluate tissues without formalin fixation, according to a UC Davis news release.

“Here, we introduce a simple, non-destructive slide-free technique that, within minutes, provides high-resolution diagnostic histological images resembling those obtained from conventional hematoxylin and eosin histology,” the researchers wrote in their paper, published in Nature Biomedical Engineering.

High-resolution Biopsy Images in Minutes

The UV microscope relies on technology that UC Davis researchers dubbed MUSE, which stands for Microscopy with Ultraviolet Surface Excitation. According to the researchers, MUSE produces high-resolution images of biopsies and other fresh tissue samples that are ready for a pathologist’s review within minutes.

“MUSE eliminates any need for conventional tissue processing with formalin fixation, paraffin embedding, or thin-sectioning. It doesn’t require lasers, confocal, multiphoton, or optical coherence tomography instrumentation. And the simple technology makes it well-suited for deployment wherever biopsies are obtained and evaluated,” stated Richard Levenson, MD, MUSE Microscopy CEO, Professor, and Vice Chair for Strategic Technologies in the Department of Pathology and Laboratory Medicine at UC Davis, in the news release.

Ultraviolet microscopy is distinguished by its ability to magnify samples and enable views with greater resolution. This is due to the shorter wavelength of ultraviolet light, which improves image resolution beyond the diffraction limit of optical microscopes using normal white light, according to News Medical.

The unique ultraviolet light microscope tool may soon enable clinical laboratories and anatomic pathology groups to accurately report on biopsies to physicians and patients faster, for less money, and without exposure to deadly chemicals. This would be timely considering the pressure on the pathology industry to switch to value-based reimbursement from fee-for-service billing, and to embrace personalized medicine.

Richard Levenson MUSE UC Davis

“It has become increasingly important to submit relevant portion of often tiny tissue samples for DNA and other molecular functional tests,” notes Richard Levenson, MD, MUSE Microscopy CEO, Professor, and Vice Chair for Strategic Technologies in the Department of Pathology and Laboratory Medicine at UC Davis, shown above with MUSE. “Making sure that the submitted material actually contains tumor in sufficient quantity is not always easy and sometimes just preparing conventional microscope slices can consume most of or even all of small specimens. MUSE is important because it quickly provides images from fresh tissue without exhausting the sample.” (Photo and caption copyright: UC Davis.)

MUSE is being commercialized and investors sought by MUSE Microscopy, Inc.

Traditional Microscopy is Time-Consuming, Hazardous, Expensive

Light microscopy, a time-honored technology, has been available to pathologists for more than 200 years. It is the cornerstone for cancer diagnostics and pathology, the UC Davis researchers acknowledged. But it requires time-consuming and expensive processes, which are especially glaring in a resource-challenged healthcare industry, they pointed out.

“Histological examination of tissues is central to the diagnosis and management of neoplasms and many other diseases. However, commonly used bright-field microscopy requires prior preparation of micrometer-thick tissue sections mounted on glass slides—a process that can require hours or days, contributes to cost, and delays access to critical information,” they wrote in their paper.

“MUSE promises to improve the speed and efficiency of patient care in both state-of-the art and low-resource settings, and to provide opportunities for rapid histology in research,” they continued.

No Histology Slide Preparation Needed

MUSE developers also called attention to the use of hazardous chemicals, such as formalin, in lab processes, which has been linked to cancers including myeloid leukemia, nasopharyngeal cancer, and sinonasal cancer, according to a National Academy of Sciences report. Still, more than 300 million slides are prepared in the US each year at a cost of several billion dollars to the healthcare industry, according to the MUSE Website.

MUSE, however, penetrates tissue samples by using ultraviolet light at short wavelengths—below the 300-nanometer range. The MUSE ultraviolet microscope can reach several microns-deep into tissues.

That’s enough, the researchers claim, to be comparable with the thickness of tissue slices anatomic pathologists use with traditional microscope slides. However, MUSE requires no conventional tissue processing associated with histology slides.

How Does it Work?

MUSE is comprised of an optical system with UV light-emitting diodes (LEDs), a UV compatible stage, and a conventional microscope. That’s according to Photonics Online, which described the process:

  • “UV light at 280 nanometer spectral range illuminates about one square millimeter of specimen;
  • “Surface is limited to a few nanometers deep to make high-contrast images possible;
  • “Excitation light, at sub-300 nanometer spectral region, elicits bright emission from tissue specimens;
  • “Specimens, which were stained with conventional florescent dyes, emit photons;
  • “Photons are captured using glass-based microscope optics;
  • “A Python programing language solution, with a graphics unit, converts MUSE images in real-time;
  • “Images are comparable to the hematoxylin and eosin versions histologists and pathologists are accustomed to.”

The result, according the MUSE website, “is stunning detailed images conveying a degree of resolution, structure, and depth unachievable until now by any single technology.”

Other Alternative Histology Processes Under the Microscope

MUSE is not the only approach being studied that could create cellular images without sectioning tissue samples. Anatomic and histopathology laboratory leaders looking to differentiate their labs should keep watch on the development of MUSE and other alternatives to current histology methods, especially once these new devices become green-lighted by the Food and Drug Administration (FDA) for use in patient care.

—Donna Marie Pocius

Related Information:

Microscope That Uses Ultraviolet Instead of Visible Light Emerging as Powerful Diagnostic Tool

Microscope with Ultraviolet Surface Excitation for Rapid Slide-Free Histology

Ultraviolet Microscope to Dramatically Speed-up Lab Tests

What is Ultraviolet Microscopy?

Europe Implements New Anatomic Pathology Guidelines to Reduce Nurse Exposure to Formaldehyde and Other Toxic Histology Chemicals

National Academy of Sciences Confirms That Formaldehyde Can Cause Cancer in a Finding That Has Implications for Anatomic Pathology and Histology Laboratories

Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene

Breast Cancer Surgery May Soon Be Completed Successfully without Requiring Clinical Laboratory Testing and Pathology Reports

Proof-of-concept research investigates whether photoacoustic imaging can be used in place of traditional tissue staining procedures during cancer surgery to determine if all of the tumor has been removed

Determining where breast cancer ends and healthy tissue begins is a critical part of breast cancer surgery. Surgeons are used to working closely during surgery with anatomic pathologists who generate pathology reports that specify the surgical or tumor margin, an area of healthy tissue surrounding a tumor that also must be excised to ensure none of the tumor is left behind. This helps prevent the need for follow-up surgeries and involves quick work on the part of medical laboratories.

Thus, any technology that renders such a pathology report unnecessary, though a boon to surgeons and patients, would impact labs and pathology groups. However, such a technology may soon exist for surgeons to use during breast cancer surgery.

Assessing Tumor Margin with Light During Surgery

A proof-of-concept study undertaken by researchers at Washington University School of Medicine in St. Louis (WUSTL) and California Institute of Technology (Caltech) has been looking at ways photoacoustic and microscopy technologies could enable surgeons to quickly and accurately assess the tumor margin during breast cancer surgeries. The research suggests it could be possible for surgeons to get answers about critical breast tumor margins without employing a clinical laboratory test.

This new technique based on light and sound uses photoacoustic imaging. The researchers scanned a tumor sample and produced images with enough detail to show whether the tumor was completely removed during surgery, a WUSTL news release explained.

The researchers scanned slices of tumors secured from three breast cancer patients. They also compared their results to stained specimens.

The photoacoustic images matched the stained samples in key features, according to the WUSTL news release. And the new technology produced answers in less time than standard analysis techniques. But more research is needed before photoacoustic imaging is used during surgeries, researchers noted.

“This is proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing,” Novack added.

A new imaging technique based on light and sound produces images doctors can use to distinguish cancerous breast tissue (below the dotted blue line) from normal tissue more quickly than is currently possible. The new technique (right) produces images as detailed and accurate as traditional methods (left) but in less time, according to the researchers. If such technology were eventually approved for clinical use, it would reduce the need for pathologists to analyze frozen sections while a patient was still in surgery. (Caption and photo copyright: WUSTL/Terence T. W. Wong.)

Once ready, this technology may well change how surgeons and pathologists collaborate to treat breast cancer patients and those with other chronic diseases that include growths that must be excised from the body.

Current Pathology Procedures Take Time, Not Always Useful During Cancer Surgery

At present, standard breast cancer operation procedures involve surgical and pathology teams working simultaneously while the breast cancer patient is in surgery.

Excised tissue is frozen (surrounded by a polyethylene glycol solution), sliced into wafers, stained with a dye, and microscopically analyzed by the pathologist in the clinical laboratory to determine if all cancerous tissue has been removed by the surgeon.

“The procedure takes about 10 to 20 minutes. However, freezing of tissue can result in some distortion of cells and some staining artifact. That is why frozen sections are often preliminary—with a final diagnosis based on routine processing of tissue,” according to LabTestsOnline.

Additionally, fatty breast specimens do not make good frozen sections, which requires surgeons to complete procedures uncertain about whether they removed all of the cancer, the researchers noted.

“Right now, we don’t have a good method to assess margins during breast cancer surgeries,” stated Rebecca Aft, MD, PhD, Professor of Surgery at WUSTL and co-senior study author.

Up to 60% of Breast Cancer Patients Require Follow-up Surgeries

More than 250,000 people in the US are diagnosed with breast cancer each year, and about 180,000 elect to undergo surgery to remove the cancer and preserve healthy breast tissue, WUSTL reported. However, between 20% to 60% of patients learn later they need more surgery to have additional tissue removed when follow-up lab analyses suggest tumor cells were evident on the surface of a tissue sample, Caltech noted in a news release.

“What if we could get rid of the waiting? With three-dimensional photoacoustic microscopy, we could analyze the tumor right in the operating room and know immediately whether more tissue needs to be removed,” noted Lihong Wang, PhD, Professor of Medical Engineering and Electrical Engineering in Caltech’s Division of Engineering and Applied Science. Wang conducted research when he was a Professor of Biomedical Engineering at University of Washington’s School of Engineering and Applied Science.

“Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment,” the study authors penned in Science Advances.

What is Photoacoustic Imaging and How Does it Work?

Photoacoustic imaging’s laser pulses create acoustic waves within tissue, which make way for intraoperative images with enough detail to expose cancerous tissue as compared to healthy tissue, explained a Medgadget article.

The graphic above shows elements of the photoacoustic microscopy system for surgical margin imaging developed by researchers at University of Washington School of Medicine in St. Louis and California Institute of Technology. (Photo Credit: Science Advances)

According to the Caltech news release:

·       Photoacoustic imaging (also called photoacoustic microscopy or PAM by the researchers) employs a low energy laser that vibrates a tissue sample;

·       Researchers measure ultrasonic waves emitted by the vibrating tissue;

·       Photoacoustic microscopy reveals the size of nuclei, which vibrate more intensely than nearby material;

·       Larger nuclei and densely packed cells characterize cancer tissue.

“It’s the pattern of cells—their growth pattern, their size, their relationship to one another—that tells us if this is normal tissue or something malignant,” said Deborah Novack, MD, PhD, WUSTL Associate Professor of Medicine, Pathology, and Immunology, and co-senior author on the study.

Whether in surgical suites or emergency departments, technological advancements continue to bring critical information to healthcare providers at the point of care, bypassing traditional medical laboratory procedures that cost more and take longer to return answers. Successful development of this technology would create new clinical collaborations between surgeons and anatomic pathologists while improving patient care.

—Donna Marie Pocius

Related Information:

New Imaging Technique Aims to Ensure Surgeons Completely Remove Cancer

Understanding Anatomic Pathology

Cutting Down on Cancer Surgeries

Fast Label-Free Multilayered Histology-Like Imaging of Human Breast Cancer by Photoacoustic Microscopy

Optoacoustics May Allow Surgeons to See Tumor Margins, Accurate Incisions

Researchers at ORNL Blend Microscopy and Mass Spectrometry to Create a Tool That Simultaneously Identifies and Chemically Analyzes Substances

Oak Ridge National Laboratory sees potential for clinical laboratories and pathology groups to control disease and assess treatments

What do you get by blending microscopy with mass spectrometry? A new multi-tasking tool for studying disease progression and response to treatments in patients.

Combining these two technologies into a single device could also have uses for clinical laboratory scientists and pathologists. However, much research must be done before such a device is ready to obtain FDA clearance for use in clinical settings by the nation’s medical laboratories.

The new device was created by researchers at Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tenn. They created an imaging system that supplies microscopy with spatially resolved chemical analyses.

This new development will be of high interest to surgical pathologists who work with microscopes and clinical chemists who currently perform mass spectrometry testing. It shows how one research effort has the potential to bring together two technologies regularly used in laboratory medicine. (more…)

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