Q: Can advanced medical imaging like microCT accelerate preclinical trials? A: Yes.

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Preclinical testing and training industry leader T3 Labs and imaging and image analysis experts ImageIQ use advanced quantitative imaging to accelerate preclinical research for medical device and pharmaceutical innovators, bring welcome evolution to regulatory processes and data quality.

The challenge – speeding up the medtech development cycle

Medical device and biologic innovators, especially in the orthopaedic realm, face a long, costly process advancing their products from concept-to-cure. Currently the FDA recommends histomorphometry to assess bone formation, apposition and resorption. Histology is a process that commonly requires a very large amount of time and funding, so much so that many researchers are forced to sub-sample their 3D specimens with 2D data due to resource constraints. As a result, the data that is driving R&D and commercialization decisions can be underpowered and doesn’t expound the entire product efficacy story. Further, traditional histomorphometry approaches often generate data that is qualitative, subjective and 2-dimensional.

Further, the processing of those images and the associated analysis can be painfully slow and in many cases subject to detrimental observer-based bias and variability – a simple issue of the human eye and brain. After all, skilled human observers are great at being inconsistently inconsistent.

The faster a new product gets to market, the greater the opportunity for successfully improving patient outcomes and lives, and the success of medtech innovation industry on a local, regional and national scale.

The solution – In some cases, good 3D data allows us to reduce the amount histology that needs to be performed. We’re seeing more and more sponsors leverage 3D imaging like microCT, and the FDA just recently included microCT in its new preclinical testing draft guidance document.

ImageIQ, a Cleveland Clinic Innovations imaging CRO and software company, has translated a previously manual, subjective, time-consuming process into an automated function using customized software algorithms that perform the same analysis more consistently producing data that is objective, quantitative and backed by strong validation.

“Volumetric image analysis, including microCT and other advanced modalities like high-field MRI, can deliver more comprehensive data, compared to traditional histology,” says ImageIQ Vice President Brett Hoover. “Instead of looking at a few representative images here and there, microCT can generate data from hundreds and even thousands of image slices, thus providing a more global tissue-level view of each specimen. Combining this with automated quantitative image analysis should produce more powerful data that will enable better decisions and faster translation from preclinical research to clinical trials.”

T3 Labs and ImageIQ have collaborated on imaging for preclinical projects including polymer and titanium implants and biologics intended to support and accelerate bone healing.

“We have learned that histology often does not tell us the full story,” Brett says. “But histology and histomorphometry have been the gold standard for many years, and industry can be slow to change and adopt new innovations. At ImageIQ, we’ve developed methods and technology to quantitatively correlate 2D histology data with 3D microCT data, and demonstrate that these two imaging modalities can complement each other and, in turn, generate data that can potentially strengthen the product safety and efficacy story. In some cases, good 3D data allows us to reduce the amount histology that needs to be performed. We’re seeing more and more sponsors leverage 3D imaging like microCT, and the FDA just recently included microCT in its new preclinical testing draft guidance document. I believe the popularity of 3D quantitative imaging will only continue to increase. Medtech innovators should seriously consider it in their product development plans.”

[See “General Considerations for Animal Studies for Medical Devices | Draft Guidance for Industry and Food and Drug Administration Staff,” Oct. 14, 2015”]

“Our imaging capabilities for preclinical research in almost any therapeutic area at T3 Labs are second-to-none,” says Evan Goldberg, orthopaedic and spine program director for T3 Labs. “When preclinical sponsors supplement imaging generated at T3 with quantitative image analysis from ImageIQ, data that previously took months to obtain now arrives almost overnight, and at higher scientific quality.”

The results: T3 Labs’ advanced medical imaging like microCT for preclinical, supplemented by quantitative software-driven image analysis provided by ImageIQ, is a high-value investment capable of accelerating the time-to-market for medical devices and biologics.

For one T3 preclinical sponsor in orthopaedic medical devices, specimens were already embedded for histology. However, the university lab had capacity for just one scan per day. The sponsor needed a better solution. T3 scanned 30 samples in fewer than four days. ImageIQ then custom built and validated the image processing algorithm and provided the quantitative image analysis. Together, the team delivered all of the analysis data the sponsor needed, and more. The quality of the imagery and analysis enabled the sponsor to determine they could omit originally planned histology and microscopy, thus saving them several months and tens of thousands of dollars.

Unbeknownst to Brett, one ImageIQ customer “blind tested” a combined histology micro-CT analysis data set supporting 510(k) submissions for spine and tibial indications for a bone void filler. For one indication, the quantitative histology / micro-CT software-based analysis data was included in the submission. For the other indication, the submission only included the traditional human observer-based histomorphometry data.  The FDA approved the former, but not the latter. The FDA’s response was essentially: “Why would you provide the advanced quantitative image analysis data for one application, but not the other?”

The device manufacturer then added the quantitative histology / micro-CT analysis data to the rejected application, which was then resubmitted and subsequently approved.

“MicroCT data also has the potential to show that you need fewer patients in your clinical trial,” Brett says. “We’ve shown that there is a high correlation between preclinical microCT data and clinical CT data in bone healing studies. In some cases, the preclinical data may be leveraged to power the subsequent clinical trial, and even potentially justify a smaller patient cohort.”

“T3 Labs’ prowess for preclinical research including its surgical suite, animal husbandry infrastructure, experimental expertise and microCT imaging capabilities is outstanding. I feel that T3 Labs’ preclinical imaging like microCT, supplemented by quantitative software-driven image analysis provided by ImageIQ, is a high-value investment capable of accelerating the time-to-market for medical devices and biologics.”

To learn more about advanced imaging and analysis to accelerate preclinical trials through advanced imaging and analysis, contact Evan Goldberg via email: evan.goldberg@t3labs.org Also visit https://www.imagequantify.com/