Imaging  

Tumors are often surrounded and invaded by bone marrow-derived cells. Imaging the infiltration of such immune cells into tumors may therefore be an attractive means of detecting tumors or of tracking the response to anticancer therapy. A new imaging technique may now make this possible.

Using a new approach has allowed real-time imaging of the immune system’s response to the presence of tumors—without the need for blood draws or invasive biopsies. The method offers a potential breakthrough both in diagnostics and in the ability to monitor efficacy of cancer therapies.

The method, developed in the lab of Whitehead Institute Member Hidde Ploegh and reported in the Proceedings of the National Academy of Sciences (PNAS), harnesses the imaging power of positron emission tomography (PET), which is normally used to monitor cancer metabolism, to identify areas of immune cell activity associated with inflammation or tumor development.

“Every experimental immunologist wants to monitor an ongoing immune response, but what are the options?” Ploegh asks rhetorically. “One can look at blood, but blood is a vehicle of transport for immune cells and is not where immune responses occur. Surgical biopsies are invasive and non-random, so, for example, a fine-needle aspirate of a tumor could miss a significant feature of that condition.”

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In search of a better monitoring approach Ploegh leveraged two research tools that have become staples in his lab in recent years. The first exploits so-called single-domain antibodies known as VHHs, derived from the heavy chain-only antibodies made by the immune systems of animals in the camelid family. Ploegh’s lab immunizes alpacas to generate VHHs specific to immune cells of interest. The second tool, known as sortagging, labels the VHHs in site-specific fashion to enable the tracking of the VHHs and their targets in a living animal.

"We’re very excited about this because it’s a powerful approach to pick up inflammation in and around the tumor."

Knowing that the tissue around tumors often contains immune cells such as neutrophils and macrophages, Ploegh and his lab members hypothesized that appropriately labeled VHHs might allow them to pinpoint tumor locations by finding the tumor-associated immune cells. Ploegh notes that VHHs’ extremely small size—approximately one-tenth that of conventional antibodies—are likely responsible for their superior tissue penetration and thus makes them particularly well suited for such use.

For the current research, the lab generated VHHs that recognize mouse immune cells, then labeled these VHHs with radioisotopes, and injected them into tumor-bearing mice. Subsequent PET imaging detected the location of immune cells around the tumor quickly and accurately.

“We were able to image tumors as small as one millimeter in size and within just a few days of their starting to grow,” says Mohammad Rashidian, a postdoctoral researcher in Ploegh’s lab and first author of the PNAS paper. “We’re very excited about this because it’s a powerful approach to pick up inflammation in and around the tumor.”

Rashidian and Ploegh believe that with further refinement, the method could be used to monitor response to—and perhaps modify—cancer immunotherapy, which, though quite promising, has thus far met with great success in some cases, but has failed in others.


SOURCE  Whitehead Institute

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 Imaging  

Researchers have captured the first X-ray portraits of living bacteria, detecting signals from features as small as 4 nanometers, or 4 billionths of a meter.  This milestone sets the stage for X-ray explorations of the molecular machinery at work in viral infections, cell division, photosynthesis and other processes that are important to biology, human health and our environment.

Researchers working at the Department of Energy’s SLAC National Accelerator Laboratory and Uppsala University have taken the first X-ray portraits of living bacteria.

This milestone, reported in the journal Nature Communications, is a first step toward possible X-ray explorations of the molecular machinery at work in viral infections, cell division, photosynthesis and other processes that are important to biology, human health and our environment. The experiment took place at SLAC’s Linac Coherent Light Source (LCLS) X-ray laser, a DOE Office of Science User Facility.

“We have developed a unique way to rapidly explore, sort and analyze samples, with the possibility of reaching higher resolutions than other study methods,” said Janos Hajdu, a professor of biophysics at Uppsala University in Sweden, which led the research. “This could eventually be a complete game-changer.”

The experiment focused on cyanobacteria, or blue-green algae, an abundant form of bacteria that transformed Earth’s atmosphere 2.5 billion years ago by releasing breathable oxygen, making possible new forms of life that are dominant today. Cyanobacteria play a key role in the planet’s oxygen, carbon and nitrogen cycles.

Researchers sprayed living cyanobacteria in a thin stream of humid gas through a gun-like device. The cyanobacteria were alive and intact when they flew into the ultrabright, rapid-fire LCLS X-ray pulses, producing diffraction patterns recorded by detectors.

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The diffraction patterns preserved details of the living cyanobacteria that were compiled to reconstruct 2D images. Researchers said it should be possible to produce 3D images of some samples using the same technique.

The technique works with live bacteria and requires no special treatment of the samples before imaging. Other high-resolution imaging methods may require special dyes to increase the contrast in images, or work only on dead or frozen samples.

The technique can capture about 100 images per second, amassing many millions of high-resolution X-ray images in a single day. This speed allows sorting and analysis of the inner structure and activity of biological particles on a massive scale, which could be arranged to show the chronological steps of a range of cellular activities.

In this way, the technique merges biology and big data, said Tomas Ekeberg, a biophysicist at Uppsala University. “You can study the full cycle of cellular processes, with each X-ray pulse providing a snapshot of the process you want to study,” he said.

"We have developed a unique way to rapidly explore, sort and analyze samples, with the possibility of reaching higher resolutions than other study methods. This could eventually be a complete game-changer."

Hajdu added, “One can start to analyze differences and similarities between groups of cellular structures and show how these structures interact: What is in the cell? How is it organized? Who is talking to whom?”

While optical microscopes and X-ray tomography can also produce high-resolution 3D images of living cells, LCLS, researchers say, could eventually achieve much better resolution – down to fractions of a nanometer, or billionths of a meter, where molecules and perhaps even atoms can be resolved.

LCLS is working with researchers to improve the technique and upgrade some instruments and the focus of its X-rays as part of the LCLS Single-Particle Imaging initiative, formally launched at SLAC in October in cooperation with the international scientific community. The initiative is working toward atomic-scale imaging for many types of biological samples, including living cells, by identifying and addressing technical challenges at LCLS.




SOURCE  SLAC National Accelerator Laboratory

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 Medicine  

In hospitals and medical facilities of the not-too-distant future, medical imaging will be way beyond the realm of the traditional X-ray.  Already the latest generation of CT scanners is providing an unparalleled view inside our bodies, aiding diagnosis and treatment.

The ability to explore inside the human body non-invasively is a modern day medical miracle. Computed Tomography, or CT scans, as they’re more commonly known, use radiation to see inside a patient’s body.

CT scanners are often the first imaging technology many patients encounter when doctors suspect serious disease or injury. The machines use a narrow beam of X-rays processed by a computer to create slices of the body and assemble them into detailed 3D images.
Using computed tomography, doctors track organ function in real-time and do things science fiction writers in decades past could have only dreamed about.

Circle of Willis 

The set of high-resolution CT scan images in this post come from GE Healthcare’s Revolution CT, which was unveiled in a hospital setting for the first time in September of last year at West Kendall Baptist Hospital in Florida.

GE's Revolution CT delivers uncompromised image quality and clinical capabilities through the convergence of coverage, spatial and temporal resolution.

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The scanner not only produces high-quality shots of the organs, but delivers lower doses of radiation to achieve them, putting patients at greater ease and less risk.

“According to our physicians, patient feedback about their experience with the Revolution CT has been uniformly positive,” said Javier Hernández-Lichtl, CEO of West Kendall Baptist, in a GE company report. “The advanced design definitely makes for a less intimidating, more comfortable patient experience, while yielding amazingly accurate and detailed images.”

Physicians have already collected images of major blood vessels, organs, bones, and tissues. They can watch blood pump through patients’ veins and see recently installed hardware, like coronary stents, keep arteries clear as oxygen-rich blood enters the heart.

In addition, the speed of the new technology allows providers to gather information about function as well as anatomy, enabling a comprehensive stroke assessment of the brain in a single exam.

“A core component of our strategy at GE Healthcare,” said Jeff Immelt, GE chairman and CEO, “is to partner with customers to understand their clinical and operational needs, and in turn develop next-generation technology that deliver the necessary outcomes.”

SOURCE  Business Wire, GE Healthcare

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 Microscopy  

Nanolive’s new microscope technology offers unperturbed and hitherto unperceived insights into living cells.  Observations are completely non-invasive to the cell and allow resolving the cell’s parts down to sizes of 70nm.

N

anolive SA, a start-up company founded last year at the EPFL Innovation Park in Lausanne, Switzerland, has developed a revolutionary microscope which, for the very first time, allows the exploration of a living cell in 3D without damaging it.

"You really need to be able to look at living cells because life is animate — it’s what defines life."

While scientists may still obtain a finer resolution using an electron microscope, this approach cannot be used to examine cells which are alive. For a long time, it was believed to be impossible to look inside a living cell using light microscopes due to their physical limitations. This year’s Nobel Prize for chemistry was awarded to S. Hell, E. Betzing and W. Moerner, who did not believe these presumed limitations and made revolutionary discoveries in the field of fluorescent microscopy.

While their research was focused on the chemistry of single molecules and their pathways inside living cells, Nanolive focuses on the physical structure of the living cell itself.

Fig. Mouse reticular fibroblast imaged with the 3D Cell Explorer. 

As a result, Nanolive’s technology can offer unperturbed and hitherto unperceived insights into the living cell: no longer a need for any special procedures or intensive and time-consuming preparation. As no chemistry or marker is used at all, observations are completely non-invasive to the cell and allow resolving the cell’s parts down to sizes of 70nm. This discovery has been published in Nature Photonics in January 2013.

Below, left, is shown the example of a fixed fibroblast chemically stained to identify membrane (green) and nucleus (blue). To the right is the same cell imaged with Nanolive’s 3D Cell Explorer, stained only digitally. In the first case, the preparation procedure killed the cell and took more than four hours. Using Nanolive’s technology, the same result took just five minutes and would have been possible on unstained, living cells.

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“You really need to be able to look at living cells because life is animate — it’s what defines life,” Eric Betzig stated in a recent interview.

The 3D Cell Explorer caters to this desire by displaying the cell in a completely new way with a comprehensive representation of its morphology. Since the cell is the basis of all life on earth, this is a major milestone in the history of microscopy, which may change all the rules in the fields of education, biology, pharmaceutics and cosmetics in labs and industry.

Hell said that a close look can shed light on disease: “Any disease, in the end, can be boiled down to a malfunctioning of the cell,” he said. “And in order to understand what a disease actually means, you have to understand the cell and you have to understand the malfunction.”

The 3D Cell Explorer is based on an enabling technology that overcomes the limitations of light. Similar to a MRI/CT scan in hospitals for the human body, our product takes a complete tomographic image of the refractive index within the living cell. For the first time ever you can actually look inside the cell and discover its interior such as its nucleus and its organelles. Thanks to the 3D Cell Explorer, never again researchers will have to guess what happens inside a living cell. They will actually see and precisely measure the impact of stimuli and drugs on cells, thus enabling completely new fields of research and smarter products.

Nanolive just launched its brand new website: www.nanolive.ch including a direct web store and a cell gallery where to find more astonishing cell images and timelapse movies http://nanolive.ch/cell-gallery/.




SOURCE  Nanolive

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 Medicine  

A team of international researchers have made a discovery that may lead to the curing of diseases such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease (mad cow disease) through photo therapy.

Researchers at Chalmers University of Technology in Sweden, together with researchers at the Polish Wroclaw University of Technology, have made a discovery that may lead to the curing of diseases such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease (mad cow disease) through photo therapy.

The researchers discovered, as they show in the journal Nature Photonics, that it is possible to distinguish aggregations of the proteins, believed to cause the diseases, from the the well-functioning proteins in the body by using multi-photon laser technique.

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"Nobody has talked about using only light to treat these diseases until now. This is a totally new approach and we believe that this might become a breakthrough in the research of diseases such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease. We have found a totally new way of discovering these structures using just laser light", says Piotr Hanczyc at Chalmers University of Technology.

If the protein aggregates are removed, the disease is in principle cured. The problem until now has been to detect and remove the aggregates.

The researchers now harbor high hopes that photo acoustic therapy, which is already used for tomography, may be used to remove the malfunctioning proteins. Today amyloid protein aggregates are treated with chemicals, both for detection as well as removal. These chemicals are highly toxic and harmful for those treated.

With multi photon laser the chemical treatment would be unnecessary. Nor would surgery be necessary for removing of aggregates. Due to this discovery it might, thus, be possible to remove the harmful protein without touching the surrounding tissue.

These diseases arise when amyloid beta protein are aggregated in large doses so they start to inhibit proper cellular processes.

Different proteins create different kinds of amyloids, but they generally have the same structure. This makes them different from the well-functioning proteins in the body, which can now be shown by multi photon laser technique.



SOURCE  PhysOrg

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