These are exciting times for micro computed tomography (microCT) scanning for in vivo animal–imaging. Traditional microCT scanning is an X-ray technique in which multiple in vivo images are taken of animals and mathematically combined to form a three-dimensional image of the subject. Systems are generally used in evaluations of potential drug compounds for safety and efficacy. In 2009, the initial systems market for microCT was valued at $32 million, and is estimated to grow in the high teens in 2010. The entrance of new companies in the market, introduction of new technology for CT scanning and improvements to existing technology to overcome drawbacks are expected to grow the microCT market.

With the introduction of Endra Life Sciences’ Nexus128 in April, the types of technologies used for microCT have expanded. The system combines optical and ultrasound technology with acoustic capabilities in order to generate data that are mathematically reconstructed in a method similar to X-ray CT systems. Although the Nexus 128 operates much differently than X-ray CT systems, Endra already has a built in customer base for the new technology. The company was spun off from Enlight Biosciences, a firm specializing in commercializing promising academic technologies. To choose technologies, Enlight first gathers feedback from its six pharmaceutical partners, which include Merck, Pfizer and Eli Lilly, about instruments and assays that the companies view as necessary to hasten drug discovery and development.

Endra is the first spin-off company of Enlight. “Endra was formed out of an interest by one of the Enlight partners in exploring the potential for photoacoustic imaging as a molecular-imaging technology,” explained Mike Thornton, CEO of Endra. “They wanted an instrument that would have optical absorption capabilities and be translatable to clinical applications.” The Nexus 128, Endra’s first commercial product, is priced in the $300,000 range.

The Nexus 128 was designed for use in a single application area. The system is designed for cancer research labs and oncology programs that are interested in tracking the efficacy of therapies and the normalization of tumor vasculature. “Many of the therapeutics that have been either approved or are in development target tumor vasculature in some way: whether they block ETFR cells or they normalize [the vasculature],” said Mr. Thornton. The Nexus 128’s photoacoustic technology allows for scanning at depths of up to 7 cm, which cannot be imaged by optical-imaging alternatives such as fluorescence-mediated tomography or planar fluorescence imaging. These depths can currently be reached by some imaging techniques, such as MRI and X-ray CT, but require the addition of problematic factors, such as contrast agents and radiation.

Photoacoustic CT uses an IR beam to produce thermal and acoustic impulse responses in the subject. The photoacoustic wave is then detected by an array of ultrasonic transducers placed outside the subject’s tissue, producing electric signals. These signals are amplified and digitized, and an image is mathematically formed. One of the major advantages of the Nexus 128 is that, because it does not use an X-ray source to image animals, the animals are not exposed to radiation; a concern when taking multiple X-ray CT images on a single animal. In addition, the Nexus 128 images without contrast agents, which are used for tissue imaging with CT. This keeps runs less expensive and animals in a more natural state during scanning. “Really, the differentiation in our focused application is that we don’t have to introduce an exogenous agent,” explained Mr. Thornton. “We actually use hemoglobin as the endogenous contrast to create the image of in vivo vasculature within the tumor.”

The Nexus 128 was developed for the specific application of tumor vasculature research and, unlike X-ray CT, is not a whole-body imaging system. Instead, it is designed to study an image that is, as described by Mr. Thornton, the size of a golf ball. As a result, it is less flexible in addressing other CT scanning applications, such as bone imaging.

Another recent entrant to the microCT market is no stranger to preclinical in vivo animal–imaging. Caliper Life Sciences is the leading provider of optical-imaging systems through its IVIS line of bioluminescence and fluorescence imagers. In April, the company introduced the Quantum FX, its first X-ray microCT instrument. Due to the compatability of data from different in vivo animal–imaging techniques leading to the use of multiple imaging instruments, such as optical, ultrasound and microCT, for a single study, the introduction of a microCT instrument was a natural step for the company. “By introducing the Quantum microCT, we’ve now added a three-dimensional X-ray capability to our product line,” said Will Kruka, senior vice president of Corporate Development at Caliper. “So, for morphology, for example, if we’re talking about oncology, you can see where tumor cells are active with IVIS. With Quantum, you can examine the tumor more specifically. For example, to determine the volume of that tumor,” he explained. The list price of the Quantum FX is approximately $500,000.

The Quantum allows Caliper to address applications the IVIS systems cannot, such as skeletal and cardiovascular imaging. The system also addresses some of the problems with X-ray CT: radiation and speed. The primary innovation is the reduction of radiation dosage received by animals. “The overall value proposition of the Quantum FX encompasses low dosage and that’s in the neighborhood of about 11 milligray, which is something that would allow 10 or 20, perhaps even more, CT sessions on an animal,” said Mr. Kruka. He explained that a series of design considerations, including a new flat panel detector and technology licensed from Rigaku, enabled the decrease in radiation dosage.

Another advantage of the system is its speed, which facilitates longitudinal studies with microCT systems. The Quantum FX has an 18 second scan time and a 45 second full three-dimensional reconstruction time. “Other microCT instruments can possibly perform sub-minute scans, and can definitely perform several minute scans, but generally introduce a trade-off related to animal-altering X-ray dosage and poor image quality,“ said Mr. Kruka. In addition to time savings, the speed also allows a greater number of contrast agents to be used with Quantum than with other X-ray CT instruments. “If you put human contrast imaging agents into a mouse, they clear exceptionally quickly, so with conventional preclinical in vivo animal CTs, you’re not able to use these reagents because, before the CT scan is finished, the agent has cleared,” explained Mr. Kruka. The scan time of the Quantum FX is also fast enough to allow for microCT scanning with conventional contrast agents, which are cheaper and more widely available than preclinical contrast agents.

As for the future of X-ray CT systems, Mr. Kruka believes that researchers will embrace multimodal systems. “Generally speaking, there’s no one modality that solves everyone’s problem. . . .The things we think are important are multiple modalities, increasing workflows and ease of use.”

Unlike Endra and Caliper, SkyScan has been producing microCT systems for almost 15 years. The company’s newest X-ray microCT system, the SkyScan 1176, improves the speed and decreases the radiation dosage compared to the company’s previous microCT system, the 1170. In addition to offering a line of microCT and nanoCT scanners, including compact and high-energy CTs, the company also provides microCT OEM solutions to companies such as Milabs. Skyscan’s microCT animal beds are also compatible with a number of other in vivo animal–imaging instruments to aid multi-instrument imaging workflows. Currently, 70% of the company’s clients are academic or government labs, while the remainder are companies involved in drug development.

The SkyScan 1176’s speed, which is based on its X-ray source, is the foremost innovation of the new system, according to Tom Ceulemans, CEO of SkyScan. “The X-ray source was specially developed for us to have a higher power. That means that, combined with the sensitivity of the 1176’s camera, you can reduce the scanning time by a factor of four. This means that for a full rotation of images, it only takes one minute.” Thus, the increase in throughput allows researchers to scan four times more animals than the previous SkyScan system. According to Mr. Ceulemans, the company also optimized the sensitivity of the 1176’s X-ray camera, leading to a decrease in the radiation dosage. The system price is €250,000–€280,000 ($300,000–$336,000).

In designing the 1176, SkyScan focused on diversifying the types of animals that the system can image and increasing its ease of use. The system’s bed allows for the placement of larger animals, such as rabbits or monkeys, for limb scanning. Applications with larger animals include the use of New Zealand white rabbits for orthopedic studies. Although the system comes with an in-built computer, gloved researchers can operate the major functions of the system, such as running scans and storing data, using a touch screen. In addition, the system’s tubing can be accessed and replaced through a slot, so that a lab’s own gas anesthesia equipment, perfusion agents or physiological monitoring devices can be used.

As for the future, Mr. Ceulemans points to Asia as a source of growth for the preclinical microCT in vivo animal–imaging market. “During the past three years, we’ve almost doubled the sales of scanners every year. For instance, in China you see a lot of pharmaceutical investments,” he said. “Also, academic labs in China are increasingly interested in life science investigation. Therefore, sales in China went up. Sales also increased in Japan, Taiwan and Korea.”

Chart: MicroCT Initial Systems Market

2009 2010 2011

MicroCT 32 38.05 43.83