Tracking of Red Blood Cells Using Super Resolution Ultrasound in Persons With Healthy or Overuse Injured Tendons

NCT ID: NCT06142747

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 135 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-08
• Study Completion Date: 2028-01-31

Brief Summary

The goal of this observational study is to test whether a new ultrasound method, called SUper Resolution ultrasound imaging of Erythrocytes (SURE), can image the small blood vessels found in tendons of persons with a tendon overuse injury (tendinopathy). The main questions it aims to answer are:

• Is the method sensitive enough to detect the smallest blood vessels
• What information about the blood flow can be obtained (flow velocity, pressure, shape of the vessels)
• Can the flow in an injured tendon be distinguished from that of a healthy one

Participants will receive a non-invasive ultrasound examination of their Achilles (heel) or patellar (knee) tendon, using an advanced high frequency research ultrasound system.

Researchers will compare participants with either an Achilles or patellar tendon overuse injury to participants with healthy tendons, to see if there are distinct differences in the blood vessels that could help diagnose and treat the injuries.

Detailed Description

Studies have reported an enlargement of the microvascular network in human tendons with a chronic overuse injury (tendinopathy). Ingrowth of new vessels and accompanying nerves have been proposed to be the cause of painful symptoms in patients with tendinopathy. Doppler ultrasound is the most common imaging modality to clinically investigate tendon neovascularization. This measurement is clinically useful, but its sensitivity is limited, which means that no Doppler flow is visible in healthy tendons despite invasive techniques having shown the presence of such flow. The lack of sensitivity in Doppler ultrasound means that it is impossible to accurately follow the progression from the healthy state (with zero Doppler) to a chronic state (with detectable Doppler), as well as the reverse process during healing of the injury.

The present study is designed to evaluate an ultrasound method called Super-resolution ultrasound imaging of erythrocytes (SURE), which is a new imaging technique for visualization and quantification of the microvasculature of tissues. The method is built on a technique called super-resolution ultrasound imaging (SRI), where an ultrasound contrast agent is injected into the bloodstream and tracked inside the vessels to build an image of the microvasculature. With SURE, no contrast agent is needed; it relies only on standard ultrasound to track the erythrocytes and thereby avoid invasive procedures.

The aim of this study is to determine the applicability of the SURE technique to detecting microvascular flow changes with tendinopathy by quantifying flow parameters in SURE images of healthy and tendinopathic tissues.

The study is designed as a cross-sectional, single-center, diagnostic, case-control trial on participants who are either healthy or have had a tendinopathy in their Achilles or patellar tendon. A formal sample size estimate cannot be made since the SURE method has not been clinically applied before, the sample sizes are therefore based on our experience with other outcomes for this patient group.

The study-specific medical device consists of 2 main components: a scanner system and an ultrasound probe.

• The ultrasound scanner: Vantage 256™ scanner (Verasonics, Kirkland, Washington, USA).
• The probe: Either a GE L8-18i-D linear transducer (GE Healthcare, Chicago, Illinois, USA), or a Vermon RC6gV row-column transducer (Vermon, Tours, France).

Both components are marked for conformity within the European Union (CE). The entire system (including the probe and scanner system) would classify as a Class IIa medical device, but it has not gone through a notified body as the system is not intended for commercial use.

For measurements, the participant is placed on a bed and scanned with conventional ultrasound to locate the region of tendon injury (or the thickest part of the tendon for healthy participants) and characterize it with grey-scale and Doppler imaging. The region of interest is marked on the skin and the ultrasound probe is affixed to the tendon at the specified location using a custom holder to minimize motion. The probe is then be disconnected from the conventional ultrasound scanner and connected to the Vantage 256™ scanner to record SURE images. Image data may be collected for up to 1 minute. Two scans at the same location are used for estimating repeatability. The imaging setup and image processing will be adjusted to maximize quality of the SURE images. From the images, the vessel density, and potentially other parameters (flow rate, flow orientation, vessel dimensions etc.) may be determined.

Conditions

Tendinopathy

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Control

Healthy Controls. Super-Resolution Ultrasound Imaging of Erythrocytes (SURE) of both Achilles and Patellar Tendons.

Super-Resolution Ultrasound Imaging of Erythrocytes (SURE)

Intervention Type: DIAGNOSTIC_TEST

Research ultrasound sequence for tracking erythrocytes and thereby generating a super-resolution image of the vasculature.

Tendinopathy Achilles

Patients with Achilles Tendinopathy. Super-Resolution Ultrasound Imaging of Erythrocytes (SURE) of Achilles Tendons.

Super-Resolution Ultrasound Imaging of Erythrocytes (SURE)

Intervention Type: DIAGNOSTIC_TEST

Research ultrasound sequence for tracking erythrocytes and thereby generating a super-resolution image of the vasculature.

Tendinopathy Patellar

Patients with Patellar Tendinopathy. Super-Resolution Ultrasound Imaging of Erythrocytes (SURE) of Patellar Tendons.

Super-Resolution Ultrasound Imaging of Erythrocytes (SURE)

Intervention Type: DIAGNOSTIC_TEST

Research ultrasound sequence for tracking erythrocytes and thereby generating a super-resolution image of the vasculature.

Interventions

Super-Resolution Ultrasound Imaging of Erythrocytes (SURE)

Research ultrasound sequence for tracking erythrocytes and thereby generating a super-resolution image of the vasculature.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Ultrasonography

Eligibility Criteria

Inclusion Criteria

• 18 to 70 years of age.
• BMI below 30.
• Able to lie still for 1 minute.
• Capable of providing signed informed consent.

Exclusion Criteria

• Pregnancy.
• Dementia.
• Smoking.
• Diabetes.
• Arthritis.
• Current or historical injuries to the tendon or surrounding tissue aside from tendinopathy.
• Medical or surgical treatments for their tendinopathy that may influence blood flow.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Technical University of Denmark

OTHER

Sponsor Role: collaborator

University Hospital Bispebjerg and Frederiksberg

OTHER

Sponsor Role: lead

Responsible Party

René B. Svensson

Senior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Kjaer, PhD

Role: STUDY_DIRECTOR

University Hospital Bispebjerg and Frederiksberg

Locations

Institute of Sports Medicine

Copenhagen, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Rene B Svensson, PhD

Role: CONTACT

rene.brueggebusch.svensson@regionh.dk

+45 38635870

Max FR Merkel, MSc

Role: CONTACT

max.flemming.ravn.merkel@regionh.dk

+45 38635059

Facility Contacts

Rene B Svensson, PhD

Role: primary

rene.brueggebusch.svensson@regionh.dk

+45 38635870

Max FR Merkel, MSc

Role: backup

max.flemming.ravn.merkel@regionh.dk

+45 38635059

Other Identifiers

BBH161

Identifier Type: -

Identifier Source: org_study_id

854796

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id