See the Human Cardiovascular System in a Whole New Way
Posted on by Dr. Francis Collins
Watch this brief video and you might guess you’re seeing an animated line drawing, gradually revealing a delicate take on a familiar system: the internal structures of the human body. But this movie doesn’t capture the work of a talented sketch artist. It was created using the first 3D, full-body imaging device using positron emission tomography (PET).
The device is called an EXPLORER (EXtreme Performance LOng axial REsearch scanneR) total-body PET scanner. By pairing this scanner with an advanced method for reconstructing images from vast quantities of data, the researchers can make movies.
For this movie in particular, the researchers injected small amounts of a short-lived radioactive tracer—an essential component of all PET scans—into the lower leg of a study volunteer. They then sat back as the scanner captured images of the tracer moving up the leg and into the body, where it enters the heart. The tracer moves through the heart’s right ventricle to the lungs, back through the left ventricle, and up to the brain. Keep watching, and, near the 30-second mark, you will see in closer focus a haunting capture of the beating heart.
This groundbreaking scanner was developed and tested by Jinyi Qi, Simon Cherry, Ramsey Badawi, and their colleagues at the University of California, Davis . As the NIH-funded researchers reported recently in Proceedings of the National Academy of Sciences, their new scanner can capture dynamic changes in the body that take place in a tenth of a second . That’s faster than the blink of an eye!
This movie is composed of frames captured at 0.1-second intervals. It highlights a feature that makes this scanner so unique: its ability to visualize the whole body at once. Other medical imaging methods, including MRI, CT, and traditional PET scans, can be used to capture beautiful images of the heart or the brain, for example. But they can’t show what’s happening in the heart and brain at the same time.
The ability to capture the dynamics of radioactive tracers in multiple organs at once opens a new window into human biology. For example, the EXPLORER system makes it possible to measure inflammation that occurs in many parts of the body after a heart attack, as well as to study interactions between the brain and gut in Parkinson’s disease and other disorders.
EXPLORER also offers other advantages. It’s extra sensitive, which enables it to capture images other scanners would miss—and with a lower dose of radiation. It’s also much faster than a regular PET scanner, making it especially useful for imaging wiggly kids. And it expands the realm of research possibilities for PET imaging studies. For instance, researchers might repeatedly image a person with arthritis over time to observe changes that may be related to treatments or exercise.
Currently, the UC Davis team is working with colleagues at the University of California, San Francisco to use EXPLORER to enhance our understanding of HIV infection. Their preliminary findings show that the scanner makes it easier to capture where the human immunodeficiency virus (HIV), the cause of AIDS, is lurking in the body by picking up on signals too weak to be seen on traditional PET scans.
While the research potential for this scanner is clearly vast, it also holds promise for clinical use. In fact, a commercial version of the scanner, called uEXPLORER, has been approved by the FDA and is in use at UC Davis . The researchers have found that its improved sensitivity makes it much easier to detect cancers in patients who are obese and, therefore, harder to image well using traditional PET scanners.
As soon as the COVID-19 outbreak subsides enough to allow clinical research to resume, the researchers say they’ll begin recruiting patients with cancer into a clinical study designed to compare traditional PET and EXPLORER scans directly.
As these researchers, and other researchers around the world, begin to put this new scanner to use, we can look forward to seeing many more remarkable movies like this one. Imagine what they will reveal!
 First human imaging studies with the EXPLORER total-body PET scanner. Badawi RD, Shi H, Hu P, Chen S, Xu T, Price PM, Ding Y, Spencer BA, Nardo L, Liu W, Bao J, Jones T, Li H, Cherry SR. J Nucl Med. 2019 Mar;60(3):299-303.
 Subsecond total-body imaging using ultrasensitive positron emission tomography. Zhang X, Cherry SR, Xie Z, Shi H, Badawi RD, Qi J. Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2265-2267.
 “United Imaging Healthcare uEXPLORER Total-body Scanner Cleared by FDA, Available in U.S. Early 2019.” Cision PR Newswire. January 22, 2019.
Positron Emission Tomography (PET) (NIH Clinical Center)
EXPLORER Total-Body PET Scanner (University of California, Davis)
Cherry Lab (UC Davis)
Badawi Lab (UC Davis Medical Center, Sacramento)
NIH Support: National Cancer Institute; National Institute of Biomedical Imaging and Bioengineering; Common Fund
3D Printing a Human Heart Valve
Posted on by Dr. Francis Collins
It is now possible to pull up the design of a guitar on a computer screen and print out its parts on a 3D printer equipped with special metal or plastic “inks.” The same technological ingenuity is also now being applied with bioinks—printable gels containing supportive biomaterials and/or cells—to print out tissue, bone, blood vessels, and, even perhaps one day, viable organs.
While there’s a long way to go until then, a team of researchers has reached an important milestone in bioprinting collagen and other extracellular matrix proteins that undergird every tissue and organ in the body. The researchers have become so adept at it that they now can print biomaterials that mimic the structural, mechanical, and biological properties of real human tissues.
Take a look at the video. It shows a life-size human heart valve that’s been printed with their improved collagen bioink. As fluid passes through the aortic valve in a lab test, its three leaf-like flaps open and close like the real thing. All the while, the soft, flexible valve withstands the intense fluid pressure, which mimics that of blood flowing in and out of a beating heart.
The researchers, led by NIH grantee Adam Feinberg, Carnegie Mellon University, Pittsburgh, PA, did it with their latest version of a 3D bioprinting technique featured on the blog a few years ago. It’s called: Freeform Reversible Embedding of Suspended Hydrogels v.2.0. Or, just FRESH v2.0.
The FRESH system uses a bioink that consists of collagen (or other soft biomaterials) embedded in a thick slurry of gelatin microparticles and water. While a number of technical improvements have been made to FRESH v. 2.0, the big one was getting better at bioprinting collagen.
The secret is to dissolve the collagen bioink in an acid solution. When extruded into a neutral support bath, the change in pH drives the rapid assembly of collagen. The ability to extrude miniscule amounts and move the needle anywhere in 3D space enables them to produce amazingly complex, high-resolution structures, layer by layer. The porous microstructure of the printed collagen also helps for incorporating human cells. When printing is complete, the support bath easily melts away by heating to body temperature.
As described in Science, in addition to the working heart valve, the researchers have printed a small model of a heart ventricle. By combining collagen with cardiac muscle cells, they found they could actually control the organization of muscle tissue within the model heart chamber. The 3D-printed ventricles also showed synchronized muscle contractions, just like you’d expect in a living, beating human heart!
That’s not all. Using MRI images of an adult human heart as a template, the researchers created a complete organ structure including internal valves, large veins, and arteries. Based on the vessels they could see in the MRI, they printed even tinier microvessels and showed that the structure could support blood-like fluid flow.
While the researchers have focused the potential of FRESH v.2.0 printing on a human heart, in principle the technology could be used for many other organ systems. But there are still many challenges to overcome. A major one is the need to generate and incorporate billions of human cells, as would be needed to produce a transplantable human heart or other organ.
Feinberg reports more immediate applications of the technology on the horizon, however. His team is working to apply FRESH v.2.0 for producing child-sized replacement tracheas and precisely printed scaffolds for healing wounded muscle tissue.
Meanwhile, the Feinberg lab generously shares its designs with the scientific community via the NIH 3D Print Exchange. This innovative program is helping to bring more 3D scientific models online and advance the field of bioprinting. So we can expect to read about many more exciting milestones like this one from the Feinberg lab.
 3D bioprinting of collagen to rebuild components of the human heart. Lee A, Hudson AR, Shiwarski DJ, Tashman JW, Hinton TJ, Yerneni S, Bliley JM, Campbell PG, Feinberg AW. Science. 2019 Aug 2;365(6452):482-487.
Tissue Engineering and Regenerative Medicine (National Institute of Biomedical Imaging and Bioengineering/NIH)
Regenerative Biomaterials and Therapeutics Group (Carnegie Mellon University, Pittsburgh, PA)
FluidForm (Acton, MA)
3D Bioprinting Open Source Workshops (Carnegie Mellon)
Video: Adam Feinberg on Tissue Engineering to Treat Human Disease (YouTube)
NIH Support: National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Common Fund