SITUATIONMost clinical trial sponsors and CROs find it difficult to meet regulators’ requests for quantitative imaging data during clinical development. With limited in-house imaging capabilities and reliance on manual, subjective data-generation techniques, they often turn to third-party imaging vendors. However, few of these third-party firms have the combination of deep research knowledge, advanced technology, and creative problem-solving that are critical to meeting researchers’ needs for delivering scientifically valid imaging results.

To adapt to this rapidly changing environment, ERT’s science-driven, purpose-built technology uses the latest imaging workflow management and image-analysis techniques to overcome the limitations of traditional, manual imaging approaches and provide streamlined regulatory compliance, reduced human error, and greater efficiencies throughout clinical research (Figure 1). Because ERT develops and uses its own validated software, it can quickly configure the application to meet the unique requirements of virtually any imaging study.

“No one else in the industry has the same set of core imaging capabilities, or can execute on all of the requirements of a fast-moving, technologically demanding research environment, like ERT can.” —Andrew Miesse, Engineering Manager,

Surgical Stapling Portfolio, Medtronic

Traditional Imaging Approaches:Time consuming, labor intensive, error prone

ERT’s Purpose-Built Imaging Solution:Faster, less expensive, higher quality

Manual image collection and management Sophisticated algorithm generation for each specific protocol

Time-consuming manual image assessments Validated image processing and analysis routines so readers can focus on what's critical

Unnecessary risk and delays from inconsistencies and errors Guided and intuitive read platform enables complete and consistent data

Subjective assessment with arbitrary scoring Objective results — without the typical human bias

FIGURE 1: ERT'S PURPOSE-BUILT SOLUTION OVERCOMES TRADITIONAL IMAGING LIMITATIONS

SOLVING COMPLEX CLINICAL RESEARCH CHALLENGES THROUGH SCIENTIFIC EXPERTISE AND ADVANCED IMAGING TECHNOLOGY ERT’s creativity in solving problems demonstrates product superiority for Medtronic

CASE STUDY: MEDTRONICA Medtronic business unit, formerly Covidien, partnered with ERT to develop an entirely new research approach that would help make the case for the superiority of its graduated-height surgical staples. ERT used micro-computed tomography (micro-CT) and other novel perfusion and image- analysis techniques to provide the scientific evidence Medtronic needed to support its product superiority claim, which has been published in Medical Devices: Evidence and Research.

Designing the experimentIn open and minimally invasive abdominal and thoracic procedures, the wound must be stapled firmly enough so that it doesn’t tear open, but not so firmly that it impedes blood flow to the injured area, causing improper wound healing. Medtronic set out to demonstrate that graduated-height staples with a stepped cartridge face allow more blood perfusion within the surgical staple zone than do single-height staples with a flat cartridge face. If proven correct, the graduated-height staples would reduce overall localized inflammation and lead to improved wound healing.

Conventional methods of assessing disruption of blood flow in tissue following surgery are unreliable for detection of micro-perfusion. Therefore, ERT used a quantitative method sensitive enough to measure micro-perfusion of stapled tissue: injecting a uniquely tailored barium contrast agent into the vasculature allowed for perfusion of stapled tissue to be measured radiographically using a tailored micro-CT image-acquisition protocol. Then ERT developed unique automated volumetric segmentation algorithms to pinpoint specific vascular regions of interest for quantitative evaluation (Figure 2).

Scanning and analysisERT designed the protocol, which included study rats receiving gastrectomies post-euthanization and the injection of a unique barium contrast agent. After dissection and preservation, the perfused stomachs were shipped to ERT, whose imaging experts developed the appropriate image-acquisition protocol and performed the image acquisition to ensure maximum image quality for subsequent processing and analysis. Once the 3D image-segmentation and -analysis algorithms were developed and validated, they were applied to the micro-CT volumes and analyzed automatically to generate volumetric quantitative data.

FIGURE 2: ALGORITHMS PINPOINT

VASCULAR REGIONS OF INTEREST FOR

QUANTITATIVE EVALUATION

MICRO-CT IS A HIGH-RESOLUTION 3D IMAGING TECHNIQUE USING X-RAYS TO SEE INSIDE AN OBJECT

REV 31 OCT2018 | ©2018 ERT. All r ights reser ved.

@ERTglobal@ERT

Leverage a global network of therapeutically focused clinical imaging experts

and readers

Obtain more consistent data with fewer errors

versus traditionalapproaches

Gain completeimaging-data visibility

from upload todata transfer

Achieve greater objectivity through reduced reader

adjudication and discordance

The results of the study strongly favored Medtronic’s graduated-height staples. Average perfusion volume was significantly higher with graduated-height staples (0.33%–0.18%) compared to single-height staples (0.16%–0.09%, P=0.011). The difference in average vessel-to-staple line distance was not significant, but trended lower and favored graduated-height staples (0.35–0.02 mm) compared to single-height staples (0.36–0.03 mm, P=0.18).

THE ERT DIFFERENCEIn this example, ERT leveraged several capabilities that most other third-party imaging vendors lack — for example, applying both preclinical and clinical imaging experience to solve a translational research challenge. Among these capabilities were its ability to design innovative imaging study protocols and exploratory endpoints in a previously unexplored area. ERT demonstrated that it has the right combination of scientific expertise, advanced technology, and creative problem-solving to create and successfully execute a novel study that validated a new kind of micro-CT imaging endpoint.

ERT’s research expertise, purpose-built technology, and broad imaging experience give study sponsors confidence that the design and conduct of their imaging studies will deliver the reliable data they need for new product regulatory review and approval.

Learn how to put ERT's expertise in drug, device, and biologic imaging to work for you. To learn more, go to ert.com or email info@ert.com.

FOR HIGH-QUALITY IMAGING DATA, TRANSITION TO ERT’S

SCIENCE-DRIVEN AND PURPOSE-BUILT TECHNOLOGY