Despite only using a conventional optical microscope, researchers have found a way to see farther and more detailed into what they are studying. This is by using expansion microscopy, expanding the size of what they are observing, instead of intensifying the microscope at a high cost. This technique is enabling researchers to have further access to studying breast cancer, as well as diagnosing it.
Background on the study
The study was done by an interdisciplinary research team led jointly by investigators at the Ludwig Center at Harvard and colleagues of theirs at the Massachusetts Institute of Technology, resulting in pathologists having access to a tool that is affordable, fast, and reliable. The researchers included Ludwig Harvard's Octavian Bucur and Andrew Beck, now the CEO of PathAl, and MIT's Edward Boyden and Yongxin Zhao. Best of all, pathologists will be able to use a conventional optical microscope, which most have access to already. Their findings of the new technique and its strength in in microscopic diagnosis have been published in the journal Nature Biotechnology.
Before this innovative technique, many would use electron microscopy as a solution to specimens being too small to study. However, these instruments are extremely expensive and unable to be operated by those other than specialized personnel, making them relatively unpractical. Expansion microscopy would cut costs and enable many pathologists to have access to diagnoses with higher accuracy.
Why expansion microscopy?
The optical microscope is a staple of any diagnostic pathology laboratory, but cannot study disease structures that pathologists are often interested in, such as features of the filtration systems of the kidneys or early cancerous lesions of the breast, due to the fact that they are simply too miniscule to be studied accurately. Even with some of the most advanced microscopes, cellular features can sometimes simply be too small to be studied reliably or diagnose certain diseases accurately. This allows researchers to tweak the samples in order to improve observation of their structures, without having to increase the power of microscopes themselves.
Conducting the study
The researchers clinically optimized expansion microscopy, which is a technique that Boyden developed with his team at MIT. This technique expands the physical size of specimens, meaning the biopsies were able to be reliably studied with any standard microscope that would be found in any pathology laboratory, so that additional expenses would not be necessary. Not to mention, this gives access to a wide range of pathologists as opposed to a specified few.
Edward Boyden, who is the co-director of the MIT Center for Neurobiological Engineering and an MIT professor of biological engineering, along with his team, attained a solution for how to successfully infuse biological specimens with swellable polymers evenly. The result is that when water is combined with the specimens, the volumes of the cells or tissues would expand exponentially. In 2015, they were able to depict these findings of uniform cell expansion and mouse brain tissues in the publication Science.
Boyden and his team showed that the method could be successful when exploiting a polymer network that uniformly swells inside a tissue sample. After cleaving the proteins enzymatically in the tissue, in order to prevent cracking, water combines with the sample, which has been treated with polymer to grow its best structures. After perfecting the technique, the researchers coined it as expansion microscopy.
The members of the research study from MIT then joined Andrew Beck, Octavian Bucur, and their colleagues. They, too, were interested in optimizing the method for diagnostic pathology and research. These researchers proceeded to develop a pathology-optimized expansion microscopy that was able to heighten the accuracy of computational discrimination between early pre-cancerous lesions, containing either a low or high risk for cancer transformation. They used this method on breast lesions of this type, which is known to be a highly difficult and intensive task for pathologists to undertake.
Postdoctoral fellow at the Ludwig Center at Harvard, Humayun Irshad, who developed the computational pipeline that was used in the study explains, "recent studies show that pathologists differ significantly in their diagnosis of early proliferative lesions." What this means is with the advancements set forth in this study, a significant impact on will be made on treatment choice, potentially leading to overtreatment, such as unnecessary surgeries, or the neglect of cancers that require early intervention due to being better able to treat based on accurate diagnoses. Andrew Beck explains, "we think that an improved system for differentiating early lesions will potentially prevent hundreds of thousands of misdiagnoses every year in the US." Octavian Bucur continued, "being able to eliminate the need for an electron microscope in diagnosing certain diseases will save a lot of money and enable a faster and easier diagnosis for those particular diseases."
This study also shed light on that diagnosing various kidney diseases can be performed with this technique at over 90% accuracy with expanded clinical samples and the conventional optical microscope, as shown in the study. Previously, this diagnosis would require electron microscopy. A 90% accuracy is a percentage that is often unheard of in these types of diagnoses, drastically heightened from previous methods.
Notes from the researchers
Octavian Bucur, lead author on the paper published in Nature Biotechnology, and an investigator at the Ludwig Center at Harvard and the Development of Pathology and Cancer Research Institute at Beth Israel Deaconess Medical Center explains, "the most exciting thing is that we can use physical tissue expansion to push conventional optical microscopes beyond their limits, with important applications in diagnostic pathology and research." This change in the abilities of a simple conventional microscope is likely to drastically alter who can conduct these studies, and cut costs to laboratories looking to have access to researching what was previously thought incapable on a conventional optical microscope.
Yongxin Zhao, lead author of the paper alongside Bucur, concurs, "we can apply this method to any type of clinical sample and all types of human tissues, including normal and cancerous tissues." This depicts the future of the study, and how it does not stop at studying connections with breast cancer. If Zhao is indeed correct, the study conducted by this research team may prove to be useful in diagnosing and studying other types of tissues and diseases as well.
Edward Boyden also explains the positive impact of expansion microscopy, and its significant improvement upon the resolution of conventional microscopes, by stating, "in this way, we can image large-scale biological structures--like cancers, or brain circuits--with nanoscale precision, on ordinary microscopes."
Future of expansion microscopy
Edward Boyden explains where he wants to see the study go in the future, "my hope is that with expansion microscopy, we can begin to map the building blocks of life systematically, in health and disease states."
The team is trying to spread the word of their study in order to make other pathologists aware of the new technique. They are also testing other ways that the method could be applied, such as studying drug resistance in breast cancer. If Boyden is correct, we may see this technique spread very far in its applications.