New way to enlarge tissues gives pathologists a closer look at cells
Beth Israel Deaconess Medical Center Jul 20, 2017
Investigators from Beth Israel Deaconess Medical Center (BIDMC) and the Massachusetts Institute of Technology (MIT) have developed and tested an innovative, reliable means of analyzing pre–cancerous breast lesions, diagnosing certain kidney diseases and using only a conventional light microscope. The technique  dubbed Âexpansion pathology" or ExPath  enhances pathologists diagnostic ability and could mean earlier interventions for high–risk patients.
The research team describes their joint effort in a paper published in the journal Nature Biotechnology.
The cellular features used to diagnose certain diseases are often too small to be seen through a standard light microscope. While scanning electron microscopes (SEM) can magnify objects up to 10 million times  revealing even subatomic particles in fine detail  magnification power in the millions comes with a price tag in the millions, too, making diagnosis by SEM extremely costly.
ÂWe can use expansion pathology to push conventional light microscopes beyond their current limits, which could have important applications in diagnostic pathology, said the studyÂs co–lead author, Octavian Bucur, MD, PhD, of the Department of Pathology and Cancer Research Institute at BIDMC, who is also a Ludwig Cancer Center Research Investigator. ÂWeÂre trying to replace the electron microscope  an expensive technology that requires specialized training  in the diagnosis of diseases.Â
In 2015, MIT researchers  led by the studyÂs co–senior author Edward Boyden, PhD, an associate professor of biological engineering and brain and cognitive sciences at MIT  developed a means of expanding cells and mouse brain tissue so that cells internal features could be viewed under the conventional light microscope found in most labs. The team infused the biological materials with a polymer that swells up evenly when mixed with water, similar to the absorptive material inside baby diapers.
ÂIf you can expand a tissue by one–hundred–fold in volume, all other things being equal, youÂre getting 100 times the information, said Boyden, who is also a member of MITÂs Media Lab and McGovern Institute for Brain Research. ÂNow you can make diagnoses without needing an electron microscope. You can do it with a few chemicals and a light microscope.Â
In the current paper, Bucur, Zhao and colleagues  including senior author Andrew Beck, MD, PhD, formerly of both BIDMC and Ludwig Cancer Research  optimized the technique for human clinical specimens and diagnostic purposes. In addition to testing the technique on normal and cancerous breast, prostate, lung, colon, pancreas, kidney, liver and ovarian tissues, the team created a mathematical model based on morphological features of cells nuclei to better discriminate between early, pre–cancerous lesions with high a probability of progressing to cancer and those with less probably of progressing to disease.
ÂExPath improved the computational pathology diagnosis of these notoriously hard–to–differentiate lesions said BIDMC researcher and study co–author Humayun Irshad, PhD.
ÂWe showed that expansion can help us better computationally classify these early breast lesions, said Bucur. ÂHelping physicians discriminate between lesions at high–and low–risk for cancerous transformation could mean fewer unnecessary procedures for low–risk patients and earlier interventions for those at high risk.Â
In another experiment, the researchers demonstrated that ExPath could be used to reliably diagnose kidney minimal–change disease (MCD) without the use of an electron microscope. MCD is diagnosed based on the characteristic podocyte, elongations of the cell normally too tiny to be seen through a light microscope.
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The research team describes their joint effort in a paper published in the journal Nature Biotechnology.
The cellular features used to diagnose certain diseases are often too small to be seen through a standard light microscope. While scanning electron microscopes (SEM) can magnify objects up to 10 million times  revealing even subatomic particles in fine detail  magnification power in the millions comes with a price tag in the millions, too, making diagnosis by SEM extremely costly.
ÂWe can use expansion pathology to push conventional light microscopes beyond their current limits, which could have important applications in diagnostic pathology, said the studyÂs co–lead author, Octavian Bucur, MD, PhD, of the Department of Pathology and Cancer Research Institute at BIDMC, who is also a Ludwig Cancer Center Research Investigator. ÂWeÂre trying to replace the electron microscope  an expensive technology that requires specialized training  in the diagnosis of diseases.Â
In 2015, MIT researchers  led by the studyÂs co–senior author Edward Boyden, PhD, an associate professor of biological engineering and brain and cognitive sciences at MIT  developed a means of expanding cells and mouse brain tissue so that cells internal features could be viewed under the conventional light microscope found in most labs. The team infused the biological materials with a polymer that swells up evenly when mixed with water, similar to the absorptive material inside baby diapers.
ÂIf you can expand a tissue by one–hundred–fold in volume, all other things being equal, youÂre getting 100 times the information, said Boyden, who is also a member of MITÂs Media Lab and McGovern Institute for Brain Research. ÂNow you can make diagnoses without needing an electron microscope. You can do it with a few chemicals and a light microscope.Â
In the current paper, Bucur, Zhao and colleagues  including senior author Andrew Beck, MD, PhD, formerly of both BIDMC and Ludwig Cancer Research  optimized the technique for human clinical specimens and diagnostic purposes. In addition to testing the technique on normal and cancerous breast, prostate, lung, colon, pancreas, kidney, liver and ovarian tissues, the team created a mathematical model based on morphological features of cells nuclei to better discriminate between early, pre–cancerous lesions with high a probability of progressing to cancer and those with less probably of progressing to disease.
ÂExPath improved the computational pathology diagnosis of these notoriously hard–to–differentiate lesions said BIDMC researcher and study co–author Humayun Irshad, PhD.
ÂWe showed that expansion can help us better computationally classify these early breast lesions, said Bucur. ÂHelping physicians discriminate between lesions at high–and low–risk for cancerous transformation could mean fewer unnecessary procedures for low–risk patients and earlier interventions for those at high risk.Â
In another experiment, the researchers demonstrated that ExPath could be used to reliably diagnose kidney minimal–change disease (MCD) without the use of an electron microscope. MCD is diagnosed based on the characteristic podocyte, elongations of the cell normally too tiny to be seen through a light microscope.
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