“Revolutionary” is an often overused word, applied to myriad industries and technologies. For something to be truly revolutionary, it should absolutely change the way an industry works. The introduction of the train, the car, and airplane revolutionized transportation. Nowadays, the smart phone is revolutionizing the way we communicate.
In the field of medicine—and particularly in pathology—change has been slow. In fact, one could argue that little has changed in 100 years. Pathologists still use microscopes as the gold standard for detecting and diagnosing cancer. There is good reason for this. Pathologists make the majority of their diagnoses without using any information that is empirical. They simply look at a well-stained slide and, by adjusting the focal planes on the optical instrument, can deduce from experience the likelihood of a sample being abnormal. However, pathologists have embraced additional testing to help them fully diagnose a patient’s condition to the point where in some cases, they can tell the referring physician what drug the patient is likely to respond to.
What does this have to do with imaging technology? Although the microscope continues to be the hallmark of the pathologist’s trade, technology is advancing at such a rate that applications are changing the options pathologists have in interpreting data. There are three fundamental areas where these changes are profound—and all of them revolve around transformations in imaging.
Imaging in genomic testing
Genomic sciences have profoundly changed the way we assess and evaluate cancer status. Early diagnosis and accurate staging are the fundamental drivers of these applications. Molecular imaging helps identify molecular alterations in tumor expression patterns. For pathologists, the greatest advancements have come from the use of genomic-based molecular techniques such as polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and more recently DNA sequencing. All of these techniques are applied to detect locus specific or unbalanced chromosomal abnormalities in which there is a net gain or loss of genetic material associated with a particular disease state. Each plays a role in the specific applications used by pathologists.
FISH uses fluorescently labeled probes to locate the positions of specific DNA sequences on chromosomes. This application is excellent for the detection of HER2 neu status in breast cancer or detection of the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC). PCR is most commonly used for detection of mutations associated with EGFR, BRAF, and KRAS. The applications used most are the ones that have some drug treatment option associated with them.
Array CGH and DNA sequencing move from locus specific testing to whole genome analysis where the resolution of the genome is so exquisite that it can look at DNA probes down to 25 base pairs for array CGH to single nucleotide proteins (SNPs) for DNA sequencing. The primary advantage of these latter technologies is the ability they offer to look at the entire make-up of the patient’s chromosomes in evaluating the causes and aggressiveness of specific cancers. Although relatively new to the cancer detection area, aCGH and DNA sequencing will eventually find their way into the standard of care for select cancers.
All of these technologies use some form of imaging, such as fluorescent probes and microscopes, combined with high resolution scanners to pick up fluorescent signals. The pathologist uses these technologies to augment the results from the microscope evaluation, thus providing a more complete diagnostic and prognostic picture for the referring physician.
Business applications for imaging in the lab
Just as exciting as the testing technology advancements are the logistical advancements in moving these images for evaluation. One of the quickest motivators for acceptance of new technologies is the potential to translate new developments into equity and earned revenue. In pathology, Technical Component/Professional Component (TC/PC) splits associated with “send out” tests such as those described earlier have provided the opportunity to provide an image such as FISH HER2 to a pathologist for interpretation, allowing the pathologist to read and bill for the professional component. Many AP labs offer “tech only” options to pathologists for immunohistochemistry (IHC) and some molecular testing. All use the web to give pathologists access to cases where the images are read and signed out remotely. This provides for more efficient turnaround time and flexibility in access, and serves as a revenue generator—while helping to transform the efficiency and speed of clinical diagnoses and patient care.
Digital imaging as a workflow solution
For 10 years, digital imaging has been touted as the next evolution of pathology. Radiology moved to it years ago and has never looked back. Granted, pathology is a more complicated application because one is looking across multiple focal planes, and the resolution needed to simulate what a person can look at under a microscope is not trivial. However, pioneering companies have made great strides in creating products that meet the resolution and quality criteria and in developing software and hardware to optimize scanners for workflow inclusion. The rate limiting issues affecting widespread acceptance of digital pathology in the United States at this point are cost of the scanners, FDA approval of digital images for primary diagnosis, and acceptance by the pathology community of digital imaging as a substitute for traditional slides. However, we are close—and this is a great example of a technology preparing a profession for widespread acceptance. Major technology companies have invested heavily in the field. Europe is leading the way in the use of digital scanners in hospitals.
The value of digital imaging is significant; it is potentially transforming to the entire medical industry and diagnostic process. Several scenarios best paint the picture of why the technology is so relevant. In Canada, access to pathologists in rural environments is a significant issue. A relevant case study centers on one hospital system that decided to invest in scanners for its remote operations, allowing pathologists anywhere in the country to read the cases online. This freed up valuable resources, eliminated critical care issues for frozen sections sent from the operating room, and created a network where quality-of-life issues could be addressed for practicing pathologists. In addition, the hospitals performed concordance studies to ensure the quality of the digital images was consistent. The result: a more efficient diagnostic process that saved time and money and improved clinical outcomes.
The second scenario involves the use of the cloud. Cloud technology has opened up the ability to store large digital images and make them available to anyone with secured access. By combining this with image viewing software and social networking tools, countries in desperate need of pathologists can invest in a scanner and have a subspecialist anywhere in the world read and consult on a case. This alone can generate millions of dollars of consulting work for pathologists and provide access to quality care for patients around the globe. Some American companies, as well as institutions such as the University of Pittsburgh, already have contracts with companies in China and other countries to transmit and read cases from U.S.-based pathologists.
Finally, integration of digital imaging management software within the laboratory information system (LIS) will transform how cases are managed, communicated, and stored—driving home all of this article’s themes. Imagine this scenario: a breast cancer patient sample is sent to a local pathologist in Iowa. A slide is created, stained, and scanned. Additional testing is needed, so an electronic order is made from the LIS. The receiving laboratory in California does additional molecular testing and scans the results for review by the pathologist. Without ever leaving his LIS, the pathologist reads the additional testing and incorporates the results into a comprehensive report, including an image of the FISH results. Before sending the diagnosis to the referring doctor, he accesses a pathology professional network and looks up a breast cancer specialist at the University of Southern California whom he trusts. He asks for a quick consult using a messaging tool and gives her access to the digital images surrounding this case. The consultant provides her review using the online tools provided, and the original pathologist includes the consultant information in his final report. The report is “sent” via a generated email to the referring doctor, who is on vacation in Hawaii. Using his iPhone, he goes to a secure website providing access to the LIS and his report. A phone call to the patient is then made without the referring physician ever leaving his beachside chair!
Is all this “revolutionary”? It depends on the adoption curve and the potential for significant improvement in healthcare. Clearly, incremental advances already have made the vision of the future easier to see. Cancer does not wait for technology. It is not going away. If we can devise tools that help us in this fight and slow the impact of the disease, the name we use to describe the technology is irrelevant—but the transformative impact on a massive scale is undeniable.
Dan Angress is co-founder and Chief Commercial Officer for California-based PathCentral, provider of integrated pathology outreach solutions. He has 25 years experience as a healthcare executive working in the medical laboratory sector.