3-D Visualizations for Cancer Diagnosis

University of Washington researchers have helped develop a new kind of microscope to visualize cells in three dimensions, an advance that could bring great progress in the field of early cancer detection. The technique could also bridge a widening gap between cutting-edge imaging techniques used in research and clinical practices, researchers said.

Eric Seibel, a UW mechanical engineering associate professor, and his colleagues have worked in collaboration with VisionGate, Inc., a privately held company in Gig Harbor, Wash., that holds the patents on the technology. The machine works by rotating the cell under the microscope lens and taking hundreds of pictures per rotation, and then digitally combining them to form a single 3-D image.

The 3-D visualizations could lead to big advances in early cancer detection, since clinicians today identify cancerous cells by using 2-D pictures to assess the cells' shape and size.
"It's a lot easier to spot a misshapen cell if you can see it from all sides," Seibel said. "A 2-D representation of a 3-D object is never perfectly accurate -- imagine trying to get an exact picture of the moon, seeing only one side."

The new microscope, known by the trademarked name Cell-CT, is so named because it works similarly to a CT-scan -- though on a very small scale, and using visible light instead of X-rays. In a CT-scan, the patient is immobile while the X-ray machine rotates. In the Cell-CT microscope, each cell is embedded in a special gel inside a glass tube that rotates in front of a fixed camera that takes many pictures per rotation. The gel has similar optical properties to the tube's so that no light reflects off the glass. In both processes, the end result is that hundreds of pictures are assembled to form a 3-D image that can be viewed and rotated on a computer screen.

The new 3-D microscope also helps to bring imaging techniques from the lab to the doctor's office. Although great advances have been made in microscope technology through the years, clinicians have been using essentially the same technique for cancer diagnoses for the last 300 years, Seibel said. Pathologists today still use a cell stain invented in the 1700s to examine sections of suspected cancers. Pathologists do not use any of the newer fluorescent molecular dyes that produce the precise, detailed cellular portraits found in biology journals.

"Scientists have been using fluorescent dyes in research for decades, but these techniques have not yet broken into everyday clinical diagnoses," Seibel said. "There's a big gap between the research and clinical worlds when it comes to cancer, and it's getting wider. We're trying to bridge that gap."

Part of the reason for this gap, Seibel said, is that there is no way to accurately match an image taken using the fluorescent dyes with an image taken using the traditional stains that currently form the basis for cancer diagnoses, and for which diagnostic standards exist. The new 3-D microscope will allow that matchup -- Seibel and his colleagues have shown simultaneous fluorescent and traditional staining of the same cells. The new device is the first 3-D microscope that can use both traditional and fluorescent stains, Seibel said.

"Now that we have a way to compare these stains, we hope this will provide a way to get some of those sophisticated research techniques into clinical use," Seibel said.
The new microscope is also more precise than other 3-D machines currently available. All other microscopes producing 3-D images have poor resolution in the up-down direction, the direction between the sample and the microscope's lens, Seibel said.

Qin Miao, a UW bioengineering doctoral student, used a tiny plastic particle of known dimensions to show the microscope's resolution. He found that the UW group's machine has three times better accuracy in that up-down direction than standard microscopes used in cancer detection. Miao will present the group's findings for the microscope's performance Feb. 9 at the SPIE Medical Imaging conference in Orlando, Fla.

In another recent publication, Seibel and his colleagues describe a study comparing cancer detection using traditional methods with their 3-D microscope. Pathologists using 3-D technology detected cancer with one-third the error rate compared to those using the traditional microscope. The authors also describe using their microscope to discover a "pre-cancer" cell, a cell that was on the verge of turning cancerous.

A New Generation of Materials

Scientists from the Madrid Institute of Advanced Studies in Materials (IMDEA Materiales)– in collaboration with a research group from CENIM, CSIC and the Iskra institute of Ufa, Russia – have developed a mechanical method to generate and stabilise at room temperature and atmospheric pressure crystalline phases of metals that until now have only been stable at very high pressures.

The atoms of metals are organized in ordered structures denominated crystal lattices. The geometry of the latter depends of the nature of the material as well as of temperature and pressure. At room temperature and atmospheric pressure, pure metals like gold, aluminium and copper have cubic lattices, and others like magnesium, titanium and zirconium have hexagonal structures (called alpha phases, a).

Increases in pressure occasionally cause changes in the geometry of the crystal lattice, resulting in the appearance of new phases. For example, in the case of titanium, the hexagonal a lattice, stable at 1 atm, transforms into a cubic structure (beta phase) when a hydrostatic pressure of approximately 1 million atmospheres is applied. If, once the cubic phase has been generated, the pressure is reduced down to 1 atm, the reverse transformation takes place, giving rise to the original hexagonal a phase. Due to the extreme pressure conditions needed to generate these new phases, the practical applications of these materials are very limited.

Scientists from (IMDEA Materiales) – in collaboration with the National Centre for Metallurgical Research] (CENIM) and the Iskra institute of Ufa, Russia – have developed a mechanical method to stabilise at room temperature and atmospheric pressure crystalline phases of metals that until now have only been stable at very high pressure. The method is based on simultaneously applying compression and shear strains. It has been proven that shear enhances the transformation kinetics significantly, eliminating the need for very high pressures. This technique has been successfully applied to pure titanium and zirconium and a patent application has been filed.

The high-pressure phases could have properties of great technological interest. For example, cubic titanium (beta phase) is very attractive for manufacturing bone implants, since its elastic modulus is more similar to bone than hexagonal titanium. Moreover, it is known that the critical superconducting temperature of beta titanium is also higher. This research therefore represents a first step towards manufacturing a new generation of materials with as yet unknown properties and opens the doors to their practical application.

Environment Ministers have Agreed to Negotiate Mercury Treaty

Six thousand tonnes of mercury enter the environment every year, posing a threat to human and animal health. Environment ministers meeting in Kenya have agreed to negotiate a treaty to reduce the supply and use of mercury worldwide.

The ministers from 140 countries, attending UNEP's Governing Council meeting in Nairobi Feb 16-20, reached consensus to begin negotiating a legally-binding instrument to control mercury pollution next year, leading to a treaty for signature in 2013.

Governments also agreed to increase the budget of UNEP, support renewable energy and energy efficiency, and underlined the importance of investment in a "green economy" as part of worldwide economic recovery.

Mercury is found in thermometers and household products, and is used in plastic production and mining. UNEP says of the around 6,000 tonnes of mercury entering the environment annually, some 2000 tonnes comes from power plants and coal burned in homes. The dense and highly toxic metal stays in the environment once released, travelling across the globe on air and sea currents.

"This decision to develop a mercury treaty is the first step in addressing the global mercury crisis. Levels of mercury have increased two- to three-fold in the last 200 years, to the point where large fish such as tuna, swordfish, shark, are not safe [to eat]," mercury campaigner Michael Bender told IPS.

Mercury is a dangerous neurotoxin that makes its way up to the food chain into humans. Even slight exposure to its most toxic form, methylmercury, causes irreversible damage to developing brain of children. In some countries, women of child-bearing age are advised not to eat certain types of fish with high mercury levels, particularly large predatory fish which have been established to contain high levels of mercury.

Bender, director of the Mercury Policy Project, a U.S.-based organisation promoting policies to eliminate mercury use, said, "The main concern is that pregnant mothers and foetuses are at greater risk of developing complications from consuming mercury contaminated fish."

While public awareness of poisoning from fish contamination is crucial, questions are being raised over the practicability of this dietary suggestion. "Such dietary restriction is terrible and impossible for many fisher communities in the world. For some people, because of the poverty level, fish is all they can afford because they can get it very fast straight from the water," said a statement by the Women's Major Group, comprising women present at the UNEP governing council meeting.

Another source of mercury poisioning is the substantial amounts of mercury used in mineral processing, often in highly unsafe and environmentally hazardous conditions. It is estimated that in more than 50 developing countries across Asia, Africa and South America, there are about 15 million artisanal and small-scale miners.

Upwards of 100 million people may be affected, directly and indirectly, by mercury from this sector, according to a 2007 global mercury project undertaken jointly by the Global Environment Facility, United Nations Industrial Development Organisation and the United Nations Development Programme.

"The workers are working in mines handling mercury like water; without gloves, barefoot and almost naked. They go back home with traces of mercury on their hands, putting the lives of those they live with in danger of inhaling mercury vapour," said Hemsing Hurrynag, the Africa coordinator Zero Mercury Campaign, an international coalition of 75 non-governmental organisations advocating for mercury reduction.

He says there is little awareness of the dangers of mercury both to humans and the environment in communities surrounding mines, where extensive environmental degradation and ecosystem contamination has been recorded, going on for decades after mining activities have ceased.

A UNEP 2008 publication, Mercury Use in Artisanal and Small Scale Gold Mining, states that the rising price of gold - up from 260 dollars per ounce in March 2001 to over 1000 dollars per ounce in March 2008 - has seen a gold rush involving poverty-driven miners in many countries. Small-scale mining provides an important source of income in rural communities and regions where economic alternatives are limited.

Given that emissions from one country are transported through the air water, mercury emissions are a global issue. Earlier resistance to a legally-binding treaty came from countries that are heavily dependent on coal for power generation. India and China previously supported only voluntary cuts in emissions. The new government of the United States also reversed its position, clearing the way for negotiations to begin. Under the Bush administration, the U.S. opposed any international efforts to reach legally-binding agreements such as the one now proposed for mercury.

The intended treaty is expected to reduce production of mercury, provide for safe storage of existing stockpiles and establish awareness creation mechanisms that will inform populations about the threats posed by this toxic substance.

According to UNEP's executive director, Achim Steiner, the global nature of mercury pollution requires well-coordinated international efforts that compel countries to commit to each other. And his organisation is embarking straight away on action.

Acid Rain is Affecting a Major Portion of China since Last Few Years

Acid rain caused by worsening air pollution now affects one-third of China’s landmass, threatening soil quality and food safety. In 2005, acid rain hit more than half of the 696 cities and counties under air-quality monitoring, with some cities receiving all of their precipitation as acid rain.

While air quality has improved in some areas of China as a result of adjustments in the nation’s energy structure and stricter vehicle emissions standards, 40 percent of urban air quality remains below even second-grade national standards, reflecting various levels of pollutants. Sulfur dioxide and inhalable particulate matter are the two major acid rain-causing substances.

More than 25 million tons of sulfur dioxide belched from China’s coal-fired power and coking plants last year, double the level deemed safe for the facilities` environmental capacity. The desulfurization facilities in these plants have a combined capacity of 53 million kilowatts, representing only 14 percent of total installed capacity. Shanxi Province in northeastern China, famous for its local coking industry, produced more than 80 million tons of coke (a solid carbon residue used in making steel) in 2005, emitting high levels of sulfurous compounds. Of the more than 680 coking enterprises province-wide, only 65 have applied for environmental protection examination and approval; of these, only 30—or about 5 percent of all coking enterprises—currently meet national sulfur emission standards.

Inhalable particulate matter (PM) is the primary pollutant affecting human health and urban air quality in China. In 2005, 35.8 percent of the nation’s cities suffered from PM pollution at levels below the second-grade national standards; the most polluted regions are northern Shanxi, Inner Mongolia, Ningxia, and southwestern Sichuan provinces. Inhalable PM is caused by emissions of soot (fine black particles composed chiefly of carbon, produced by incomplete combustion of coal, oil, wood, or other fuels) and industrial powders. In 2004, Chinese soot emissions topped 11.8 million tons and industrial powder emissions totaled 9.11 million tons.