Researchers Use 3D Imaging Tool To Facilitate Anti-Cancer Drug Screening

According to the World Health Organization, about 1 in 6 deaths were caused by cancer in 2015, making it one of the greatest health challenges of our time. Although the risk of getting cancer can be reduced by leading a healthy lifestyle, drug treatment remains the primary form of combatting this disease.  Unfortunately, current treatments lack efficacy against many cancers, especially at later stages.

Researchers are striving to improve anti-cancer drugs; however, low success rates, long development times, and high costs provide significant barriers in this process.  Lowering these barriers is critical towards improving the quality and quantity of clinical treatments.  In a recently published paper, researchers from Lehigh University, in Bethlehem, PA, explored how a rapidly developing three-dimensional (3D) imaging technology enables non-invasive characterization of in vitro tumor models for high throughput drug screening.

3D Tumor Spheroids

3D tumor spheroids are spherically shaped tumor cell clusters that use cells from well-established cell lines or are extracted from patients or diseased animals. They can be produced simply and rapidly outside of the body by specific culturing methods. Unlike 2D cell cultures that are commonly seen in the biology labs, 3D tumor spheroids serve as more accurate representations of human tumors, demonstrating similar nutrient gradients, oxygen and metabolic waste dynamics, and drug resistance. In this way, 3D tumor spheroids can provide more predictive value for preclinical anti-cancer drug screening.

3D culture cells. Credit: Yongyang Huang

The Technique

Researchers led by Professor Chao Zhou at Lehigh University utilized a 3D imaging technique called optical coherence tomography (OCT) to obtain high-resolution images of the inside of the spheroids. OCT is a rapidly developing optical imaging technique that works similar to ultrasound. Instead of detecting sound waves, OCT detects back-scattered light from different depths of a biological specimen.

By transverse scanning at multiple locations, a 3D structural image of the spheroid can be acquired and reconstructed in a few seconds. The reconstructed spheroid images have a micron-scale resolution in all three dimensions. Furthermore, OCT doesn’t require any labeling or contrast agents in the spheroid, which allows long-term monitoring without damaging its cell structure.

The Experiment

Researchers at Lehigh University used OCT to characterize 3D tumor spheroids that originated from brain tumors and colon tumors. They monitored the spheroids for over 21 days and observed sizes growing from ~250 μm to ~600 μm in height. They found that these two types of tumor spheroids exhibited distinctive evolutions in their geometric shapes at late growth stages: brain tumor spheroids remained tightly packed spherical shape throughout 21-day development, while colon tumor spheroids became disrupted and flattened after Day 11.

Credit: Yongyang Huang

By quantifying the growth dynamics of tumor spheroids in terms of size and volume, they demonstrated that OCT is an accurate and robust tool for spheroid imaging, even for those with asymmetric shapes. They further demonstrated that OCT can be used to identify necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation. This non-destructive necrotic region detection technique was confirmed by comparing spheroid images obtained using fluorescence, histology, and immunohistochemistry with corresponding OCT attenuation images. Researchers suggested that this method could be a promising alternative to label-free cell viability tests in tumor spheroids.

The Future

The next step in this process is to utilize OCT to evaluate how drug treatment affects the structure tumor spheroids. The researchers believe that the additional morphological and physiological information provided by this imaging technique, in addition to its high imaging speed, will directly improve efficiency and accuracy of the drug screening step.  Furthermore, screening quality will increase as OCT speed and resolution are continuously improved.

This study, Optical coherence tomography detects necrotic regions and volumetrically quantifies multicellular tumor spheroids, by Yongyang Huang, Shunqiang Wang, Qiongyu Guo, Sarah Kessel, Ian Rubinoff, Leo Li-Ying Chan, Peter Li, Yaling Liu, Jean Qiu, and Chao Zhou from Lehigh University and Nexcelom Bioscience LLC, was recently published in the journal Cancer Research.

About The Author

Yongyang Huang

Yongyang Huang received his B.S. degree in Physics at Peking University in July 2013. Since September 2013, he has been a Ph.D student in Department of Electrical & Computer Engineering (ECE) in Lehigh University.His research area is focused on optical coherence tomography (OCT) and its applications in biomedical imaging.

Speak Your Mind!


Production Of Microalgal Biomass Using Wastewater Reduces The Spread Of Antibiotic Resistance To Environment

Our contemporary society faces growing challenges related to energy production and waste management. In this context, technologies harnessing waste streams as resources for energy production are in demand. A promising example of such an approach is utilizing municipal wastewater for bioenergy production via microalgal biomass growth in photobioreactors. Wastewater use as a substrate in photobioreactors […]

How Energy And Carbon Dioxide Move Through Alpine Forests

There have been great strides in the human understanding of our impact on the global climate in recent decades. As scientists push forward with that effort, it has become necessary to improve our knowledge of the finer details of the interactions between the terrestrial biosphere and the atmosphere above. Climate models on most scales must […]

Ultrasmall Nanoplatelets: The Ultimate Tuning Of Optoelectronic Properties

 Semiconductor nanocrystals with unique optoelectronic properties have emerged as promising materials for applications in solar technologies, including solar cells, solar-driven hydrogen production, and luminescent solar concentrators. Among them, ultrathin two-dimensional (2D) semiconducting nanoplatelets (NPLs) are sheet-like structures with single- or few-layer thickness (typically less than 5 nm), with lateral size ranging from 100 nm to […]

India And Bhutan As A Model For Inter- And Intra-Regional Energy Trade

Collaboration among the countries in South Asia for inter- and intra-regional energy trade has been identified as the most cost-effective way to address growing demand, including increasing energy supply and diversifying energy sources (World Bank, 2008; SAARC Secretariat, 2010; Rahman S. H., Wijayatunga, Gunatilake, & Fernando, 2011). At present, energy trade in South Asia is […]

Nucleoli Identified As Potential Markers Of Aging

Female reproductive aging is a major issue in today’s modern society. More and more women are choosing to delay childbearing for reasons that vary from effective contraception, increased presence in the workforce, and changes in values and family structures. However, the female reproductive system is the first to age in the human body, and it […]

What Is Negative Reinforcement?

Negative reinforcement is the psychological phenomena where a behavior increases because a negative stimulus or aversive event is prevented from occurring or removed. Negative reinforcement is an aspect of operating conditioning, as defined by psychologist B. F. Skinner. Operant conditioning is a process where a specific behavior is modified, either increased or decreased, by punishment […]

The Best Way To Reduce Strain On Planet To Cease Consumption Of Meat And Dairy

An analysis on the impact of industrial farming suggests that ceasing the consumption of meat and dairy products may be the single best way to for people to reduce the impact they have on the environment. Three-Quarters Of Farmland Unnecessary? A comprehensive analysis of the overall damage that farming does to the planet suggests that […]