Tag Archives: Chulhong Kim

A nanoparticle for a medical imaging machine that doesn’t exist yet

Researchers at the University of Buffalo (New York state) have created a nanoparticle that can be detected by six imaging devices according to a Jan. 20, 2015 news item on ScienceDaily,

It’s technology so advanced that the machine capable of using it doesn’t yet exist.

Using two biocompatible parts, University at Buffalo researchers and their colleagues have designed a nanoparticle that can be detected by six medical imaging techniques:

• computed tomography (CT) scanning;

• positron emission tomography (PET) scanning;

• photoacoustic imaging;

• fluorescence imaging;

• upconversion imaging; and

• Cerenkov luminescence imaging.

The advantages are obvious should somebody, somewhere create a hexamodal (aka, multimodal, aka hypmodal) sensing device capable of exploiting the advantages of this nanoparticle as the researchers hope.

A Jan. 20, 2015 University of Buffalo news release (also on EurekAlert) by Charlotte Hsu, which originated the news item, describes the ideas underlying the research,

This kind of “hypermodal” imaging — if it came to fruition — would give doctors a much clearer picture of patients’ organs and tissues than a single method alone could provide. It could help medical professionals diagnose disease and identify the boundaries of tumors.

“This nanoparticle may open the door for new ‘hypermodal’ imaging systems that allow a lot of new information to be obtained using just one contrast agent,” says researcher Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Once such systems are developed, a patient could theoretically go in for one scan with one machine instead of multiple scans with multiple machines.”

When Lovell and colleagues used the nanoparticles to examine the lymph nodes of mice, they found that CT and PET scans provided the deepest tissue penetration, while the photoacoustic imaging showed blood vessel details that the first two techniques missed.

Differences like these mean doctors can get a much clearer picture of what’s happening inside the body by merging the results of multiple modalities.

A machine capable of performing all six imaging techniques at once has not yet been invented, to Lovell’s knowledge, but he and his coauthors hope that discoveries like theirs will spur development of such technology.

The news release also offers a description of the nanoparticles,

The researchers designed the nanoparticles from two components: An “upconversion” core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.

Each part has unique characteristics that make it ideal for certain types of imaging.

The core, initially designed for upconversion imaging, is made from sodium, ytterbium, fluorine, yttrium and thulium. The ytterbium is dense in electrons — a property that facilitates detection by CT scans.

The PoP wrapper has biophotonic qualities that make it a great match for fluorescence and photoacoustic imagining. The PoP layer also is adept at attracting copper, which is used in PET and Cerenkov luminescence imaging.

“Combining these two biocompatible components into a single nanoparticle could give tomorrow’s doctors a powerful, new tool for medical imaging,” says Prasad, also a SUNY Distinguished Professor of chemistry, physics, medicine and electrical engineering at UB. “More studies would have to be done to determine whether the nanoparticle is safe to use for such purposes, but it does not contain toxic metals such as cadmium that are known to pose potential risks and found in some other nanoparticles.”

“Another advantage of this core/shell imaging contrast agent is that it could enable biomedical imaging at multiple scales, from single-molecule to cell imaging, as well as from vascular and organ imaging to whole-body bioimaging,” Chen adds. “These broad, potential capabilities are due to a plurality of optical, photoacoustic and radionuclide imaging abilities that the agent possesses.”

Lovell says the next step in the research is to explore additional uses for the technology.

For example, it might be possible to attach a targeting molecule to the PoP surface that would enable cancer cells to take up the particles, something that photoacoustic and fluorescence imaging can detect due to the properties of the smart PoP coating. This would enable doctors to better see where tumors begin and end, Lovell says.

The researchers have provided two images,

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core. Credit: Jonathan Lovell

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.
Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging. Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging.
Credit: Jonathan Lovell

Here’s a link to and a citation for the paper,

Hexamodal Imaging with Porphyrin-Phospholipid-Coated Upconversion Nanoparticles by James Rieffel, Feng Chen, Jeesu Kim, Guanying Chen, Wei Shao, Shuai Shao, Upendra Chitgupi, Reinier Hernandez, Stephen A. Graves, Robert J. Nickles, Paras N. Prasad, Chulhong Kim, Weibo Cai, and Jonathan F. Lovell. Advanced Materials DOI: 10.1002/adma.201404739 Article first published online: 14 JAN 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.

Nanojuice in your gut

A July 7, 2014 news item on Azonano features a new technique that could help doctors better diagnose problems in the intestines (guts),

Located deep in the human gut, the small intestine is not easy to examine. X-rays, MRIs and ultrasound images provide snapshots but each suffers limitations. Help is on the way.

University at Buffalo [State University of New York] researchers are developing a new imaging technique involving nanoparticles suspended in liquid to form “nanojuice” that patients would drink. Upon reaching the small intestine, doctors would strike the nanoparticles with a harmless laser light, providing an unparalleled, non-invasive, real-time view of the organ.

A July 5, 2014 University of Buffalo news release (also on EurekAlert) by Cory Nealon, which originated the news item, describes some of the challenges associated with medical imaging of small intestines,

“Conventional imaging methods show the organ and blockages, but this method allows you to see how the small intestine operates in real time,” said corresponding author Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Better imaging will improve our understanding of these diseases and allow doctors to more effectively care for people suffering from them.”

The average human small intestine is roughly 23 feet long and 1 inch thick. Sandwiched between the stomach and large intestine, it is where much of the digestion and absorption of food takes place. It is also where symptoms of irritable bowel syndrome, celiac disease, Crohn’s disease and other gastrointestinal illnesses occur.

To assess the organ, doctors typically require patients to drink a thick, chalky liquid called barium. Doctors then use X-rays, magnetic resonance imaging and ultrasounds to assess the organ, but these techniques are limited with respect to safety, accessibility and lack of adequate contrast, respectively.

Also, none are highly effective at providing real-time imaging of movement such as peristalsis, which is the contraction of muscles that propels food through the small intestine. Dysfunction of these movements may be linked to the previously mentioned illnesses, as well as side effects of thyroid disorders, diabetes and Parkinson’s disease.

The news release goes on to describe how the researchers manipulated dyes that are usually unsuitable for the purpose of imaging an organ in the body,

Lovell and a team of researchers worked with a family of dyes called naphthalcyanines. These small molecules absorb large portions of light in the near-infrared spectrum, which is the ideal range for biological contrast agents.

They are unsuitable for the human body, however, because they don’t disperse in liquid and they can be absorbed from the intestine into the blood stream.

To address these problems, the researchers formed nanoparticles called “nanonaps” that contain the colorful dye molecules and added the abilities to disperse in liquid and move safely through the intestine.

In laboratory experiments performed with mice, the researchers administered the nanojuice orally. They then used photoacoustic tomography (PAT), which is pulsed laser lights that generate pressure waves that, when measured, provide a real-time and more nuanced view of the small intestine.

The researchers plan to continue to refine the technique for human trials, and move into other areas of the gastrointestinal tract.

Here’s an image of the nanojuice in the guts of a mouse,

The combination of "nanojuice" and photoacoustic tomography illuminates the intestine of a mouse. (Credit: Jonathan Lovell)

The combination of “nanojuice” and photoacoustic tomography illuminates the intestine of a mouse. (Credit: Jonathan Lovell)

This is an international collaboration both from a research perspective and a funding perspective (from the news release),

Additional authors of the study come from UB’s Department of Chemical and Biological Engineering, Pohang University of Science and Technology in Korea, Roswell Park Cancer Institute in Buffalo, the University of Wisconsin-Madison, and McMaster University in Canada.

The research was supported by grants from the National Institutes of Health, the Department of Defense and the Korean Ministry of Science, ICT and Future Planning.

Here’s a link to and a citation for the paper,

Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines by Yumiao Zhang, Mansik Jeon, Laurie J. Rich, Hao Hong, Jumin Geng, Yin Zhang, Sixiang Shi, Todd E. Barnhart, Paschalis Alexandridis, Jan D. Huizinga, Mukund Seshadri, Weibo Cai, Chulhong Kim, & Jonathan F. Lovell. Nature Nanotechnology (2014) doi:10.1038/nnano.2014.130 Published online 06 July 2014

This paper is behind a paywall.