One nanoparticle, six types of medical imaging

 

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. 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. In the future, patients could receive a single injection of the nanoparticles to have all six types of imaging done. 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 research, Hexamodal Imaging with Porphyrin-Phospholipid-Coated Upconversion Nanoparticles, was published online Jan. 14 in the journal Advanced Materials. It was led by Lovell; Paras Prasad, PhD, executive director of UB's Institute for Lasers, Photonics and Biophotonics (ILPB); and Guanying Chen, PhD, a researcher at ILPB and Harbin Institute of Technology in China. The team also included additionanl collaborators from these institutions, as well as the University of Wisconsin and POSTECH in South Korea. 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.

3-d printed heart created

 

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The new 3D printed heart technology will be showcased at EuroEcho-Imaging 2014, the official annual meeting of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC). Held in cooperation with the Austrian Working Group of Echocardiography, the congress takes place during 3-6 December in Vienna, Austria, at the Reed Messe Wien GmbH congress centre.

EuroEcho-Imaging is the leading congress for clinicians and scientists to present and discuss the latest research and clinical findings on echocardiography and other cardiovascular imaging techniques.

New frontiers in cardiovascular imaging will be explored through presentations on three-dimensional imaging, which is a main theme of the congress. Experts will reveal the latest developments in the technology that uses imaging data to print a 3D model of the heart.

Professor Patrizio Lancellotti, EACVI President, said: "The heart is a 3D structure that we traditionally analysed using 2D imaging including echocardiography, cardiac magnetic resonance imaging (CMR) or cardiac computed tomography (CT). But with the advent of 3D imaging, now we can clearly evaluate the structure of the heart in different planes."

He added: "An amazing advance in this field is the ability to print a 3D model of the heart. This will help clinicians doing surgical and percutaneous interventions on the mitral or aortic valve to choose the perfect size of device and plan the procedure according to the patient's anatomy. Also new is the ability to create a 3D computational model of the heart which will assist with interventions but also improve our understanding of the heart's physiology. With this novel technology we will gain insights into the interactions between the valves and the ventricles, the valves and the aorta, and the valves and the left atrium."

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Story Source:

The above story is based on materials provided by European Society of Cardiology (ESC). Note: Materials may be edited for content and length.

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With $100 Million, Entrepreneur Sees Path to Disrupt Medical Imaging

 

Will ultrasound-on-a-chip make medical imaging so cheap that anyone can do it?

• By Antonio Regalado on November 3, 2014

Why It Matters

Portable, cheap, and high-quality ultrasound could make medicine’s most commonly used imaging technique accessible to more people.

Jonathan Rothberg

A scanner the size of an iPhone that you could hold up to a person’s chest and see a vivid, moving, 3-D image of what’s inside is being developed by entrepreneur Jonathan Rothberg.

Rothberg says he has raised $100 million to create a medical imaging device that’s nearly “as cheap as a stethoscope” and will “make doctors 100 times as effective.” The technology, which according to patent documents relies on a new kind of ultrasound chip, could eventually lead to new ways to destroy cancer cells with heat, or deliver information to brain cells.

Rothberg has a knack for marrying semiconductor technology to problems in biology. He started and sold two DNA-sequencing companies, 454 and Ion Torrent Systems (see “The $2 Million Genome” and “A Semiconductor DNA Sequencer”), for more than $500 million. The profits have allowed Rothberg, who showed up for an interview wearing worn chinos and a tattered sailor’s belt, to ply the ocean on a 130-foot yacht named Gene Machine and to indulge high-concept hobbies like sequencing the DNA of mathematical geniuses.

The imaging system is being developed by Butterfly Network, a three-year old company that is the furthest advanced of several ventures that Rothberg says will be coming out of 4Combinator, an incubator he has created to start and finance companies that combine medical sensors with a branch of artificial-intelligence science called deep learning.

Rothberg won’t say exactly how Butterfly’s device will work, or what it will look like. “The details will come out when we are on stage selling it. That’s in the next 18 months,” he says. But Rothberg guarantees it will be small, cost a few hundred dollars, connect to a phone, and be able to do things like diagnose breast cancer or visualize a fetus.

Butterfly’s patent applications describe its aim as building compact, versatile new ultrasound scanners that can create 3-D images in real time. Hold it up to a person’s chest, and you would look through “what appears to be a window” into the body, according to the documents.

Concept drawings filed with the patent office by Butterfly Network show ideas for a small, 3-D ultrasound imaging device.

With the $100 million supplied by Rothberg and investors, which include Stanford University and Germany’s Aeris Capital, Butterfly appears to be placing the largest bet yet by any company on an emerging technology in which ultrasound emitters are etched directly onto a semiconductor wafer, alongside circuits and processors. The devices are known as “capacitive micro-machined ultrasound transducers,” or CMUTs.

Most ultrasound machines use small piezoelectric crystals or ceramics to generate and recieve sound waves. But these have to be carefully wired together, then attached via cables to a separate box to process the signals. Anyone who can integrate ultrasound elements directly onto a computer chip could manufacture them cheaply in large batches, and more easily create the type of arrays needed to produce 3-D images.

“The vision for this product has been around for many years. It remains to be seen whether someone can make it into a market-validated reality.”

Ultrasound is used more often by doctors than any other type of imaging test, including to view a baby during pregnancy, to find tumors in soft tissues like the liver, and more recently to treat prostate cancer by heating up cells with sound waves.

The idea for micromachined ultrasound chips dates to 1994, when Butrus Khuri-Yakub, a Stanford professor who advises Rothberg’s company, built the first one. But none have been a commercial success, despite a decade of interest by companies including General Electric and Philips. This is because they haven’t functioned reliably and have proved difficult to manufacture.

“The vision for this product has been around for many years. It remains to be seen whether someone can make it into a market-validated reality,” says Richard Przybyla, head of circuit design at Chirp Microsystems, a startup in Berkeley, California, that’s developing ultrasound systems that let computers recognize human gestures. “Perhaps what was needed all along is a large investment and a dedicated team.”

Rothberg says he got interested in ultrasound technology because his oldest daughter, now a college student, has tuberous sclerosis. It is a disease that causes seizures and dangerous cysts to grow in the kidneys. In 2011 he underwrote an effort in Cincinnati to test whether high-intensity ultrasound pulses could destroy the kidney tumors by heating them.

What he saw led Rothberg to conclude there was room for improvement. The setup—an MRI machine to see the tumors, and an ultrasound probe to heat them—cost millions of dollars, but wasn’t particularly fast, more like a “laser printer that takes eight days to print and looks like my kids drew it in crayon,” he says. “I set out to make a super-low-cost version of this $6 million machine, to make it 1,000 times cheaper, 1,000 times faster, and a hundred times more precise.”

Rothberg claims there’s a “secret sauce” to Butterfly’s technology, but he won’t reveal it. But it may have as much to do with clever device and circuit design as overcoming the physical limits and manufacturing problems that CMUT technology has faced so far.

One reason to think so is that the company’s cofounder, Nevada Sánchez, previously helped cosmologists design a much cheaper radio telescope with a signal-processing trick called a butterfly network, also the origin of the startup’s name. Also working with the company is Greg Charvat, who joined it from MIT’s Lincoln Laboratory, where he developed radar that can see human bodies even through thick stone walls (see “Seeing like Superman”).

During a visit to 4Combinator’s headquarters, which sits inside a marina in Guilford, Connecticut, Charvat and Sanchez showed off a picture of a penny so detailed you could read the letters and numbers on it. They’d taken the image this spring using a prototype chip. “The ultrasound [industry] is basically back in the 1970s. GE and Siemens are building on old concepts,” says Charvat. With chip manufacturing and a few new ideas from radar, he says, “we can image faster, with a wider field of view, and go from millimeter to micrometer resolution.”

Ultrasound works by shooting out sound and then capturing the echo. It can also create beams of focused energy—and chip-based devices could eventually lead to new systems for killing tumor cells. Small devices might also be used as a way to feed information to the brain (it was recently discovered that that neurons can be activated with ultrasonic waves).

“I think it will become better than a human in saying ‘Does this kid have Down syndrome, or a cleft lip?’ And when people are pressed for time it will be superhuman.”

Rothberg says his first goal will be to market an imaging system cheap enough to be used even in the poorest corners of the world. He says the system will depend heavily on software, including techniques developed by artificial intelligence researchers, to comb through banks of images and extract key features that will automate diagnoses.

“We want it to work like ‘panorama’ on an iPhone,” he says, referring to a smartphone function that steers a picture taker to pan across a vista and automatically assembles a composite image. But in addition to recognizing objects—body parts in the case of a fetal exam—and helping the user locate them, Rothberg says the system would also reach preliminary diagnostic conclusions based on pattern-finding software.

“When I have thousands of these images, I think it will become better than a human in saying ‘Does this kid have Down syndrome, or a cleft lip?’ And when people are pressed for time it will be superhuman,” says Rothberg.  “I will make a technician able to do this work.”

Rothberg says his incubator has started three other companies in addition to Butterfly, and he’s given each of them between $5 million and $20 million in seed capital. They include a biotechnology firm, Lam Therapeutics, working on treatments connected to tuberous sclerosis; Hyperfine Research, a startup in stealth mode that hasn’t said what type of technology it is developing; and another company that’s unnamed.