Imagelabonline & Cardiovascular


Imagelabonline & Cardiovascular initiates, designs and implements human clinical studies on cardiovascular health using non-invasive vascular imaging techniques. Partners originate from academia, governmental bodies and the food and pharmaceutical industry. Imagelabonline & Cardiovascular is based in Eindhoven and Lunteren, The Netherlands. We can be reached directly by phone through +31 6 2006 2662.

Experience in human clinical studies of our team members dates back to 1992 when the first large multicentre pharmaceutical trials with imaging biomarkers on atherosclerosis and cardiovascular disease emerged. Ever since, to provide quality assured observational data, our team has focussed on optimization and application of innovative imaging techniques and processes, standardization, validation and endpoint based QC.  


Initially, in the early atherosclerosis regression trials, coronary angiography was the method of choice to investigate disease risk and treatment efficacy. The advantage of coronary angiography is that it is readily and widely available in patients in the clinical setting and makes use of an existing hospital based infrastructure. Like all X-ray based imaging modalities however, coronary angiography is an invasive cathether based technique and requires exposure to ionizing radiation, thus raising ethical issues in follow-up trials. Most of all, angiography based techniques investigate contrast agents injected into the vascular lumen and cannot depict the early stages of atherosclerosis in the vascular wall. As a consequence, the late stages of atherosclerotic disease in patients can be investigated only.  

Vascular ultrasound Doppler velocity measurements have been around since the 1960's. The elegant technique in the hands of the skilled technician remains an important tool for clinical diagnosis and research. In the 1980's with improving transducer technology and miniaturization of electronic circuitry, in every medical specialty ultrasound imaging became increasingly used. As technology improved and the price and the size of equipment decreased, the availability of ultrasound imaging as a tool in the clinical setting and for research purposes increased. Standardized and validated cardiac and vascular ultrasound imaging scan protocols were developed and became important tools in cardiovascular clinical diagnosis, decision making. 

Contrary to the X-ray based techniques, ultrasound allows investigation of blood velocity, lumen measurements and measurements of the size, structure and elasticity of cardiac and arterial walls. As ultrasound is fully non-invasive and safe, the method allows for cardiac and vascular measurements in patients and non-patients, in those at risk an not at risk, in a cross-sectional and in a followup fashion. As the status and progression of the vascular wall can be investigated, the risk and efficacy of drugs in non-symptomatic individuals can be assessed prior to the emergence of symptomatic atherosclerotic disease. Ultrasound therefore truly opened the way to assess cardiovascular health. 

Clinical studies

Carotid ultrasound

In the early 1990's carotid arterial wall ultrasound protocols for intima-media thickness (CIMT) measurements were developed for application in pharmaceutical trials investigating lipid lowering and anti-hypertensive agents. The carotid scan and image analyses protocols were scientifically validated and standardized. The results of the ultrasound studies showed highly significant differences in change in CIMT over time, making CIMT a efficient tool to assess efficacy of anti-atherosclerotic agents. Moreover, the results of the carotid ultrasound studies correlated with coronary angiographic outcomes and assessment of cardiac left-ventricular mass. These results in clinical symptomatic patients, together with carotid ultrasound studies in healthy and those at genetic and/or multifactorial disease risk, proved CIMT a validated biomarker for present and future atherosclerotic disease risk.

Technical innovation

Initially ultrasound scans were saved on a running video tape. Off-line on a reading station, a frame grabber was used to obtain still images without too much loss of axial resolution of the interlaced video images. The storage of ultrasound images on S-VHS video tape in the early trials created considerable technical, regulatory and storage problems. The tapes were impossible to copy without a loss of quality and this could be only done in a cumbersome way at high costs. The loss of tapes miraculously never happened, but could have created a regulatory hazard in case of the pharmaceutical trials as the tapes contain the source material for, in some cases, the primary efficacy parameter.

Therefore, in 1995 Imagelabonline started using digital imaging technologies to save ultrasound scan images. For ease of use a mini-disk (MD) recorder was used. For carotid structural and functional scanning an efficient scan protocol was designed were the sonographer choose high resolution still images of pre-defined arterial wall segments from the digital cine-loop of the ultrasound instrument. For each carotid scan in a patient 8 high resolution 4:1 compressed JPEG still images - 6 B-mode and 2 M-mode images - were saved. All B-mode ultrasound still images are saved in the diastole of the vessel; the stills of the M-mode scan showed at least 2 heartbeats. A backup of the images of a scan fitted exactly on a 1.4Mb floppy disk; each floppy disk was alsu copied to a local computer and stored in the patient folder.

In the following years, this approach was applied to all imaging studies. The digital storage allowed a much more efficient workflow then the oblivious videotape approach as clinical images could be safely stored and backed up on any electronic medium without quality loss. Also, with speed and functionality of web based systems improving, the digital images could be safely stored locally and transferred from equipment of any investigational site in the world to a centralized secure server.

Process innovation

Most important, the digital approach opened the way to quality control and quality assurance measures of single and multicentre studies. The quality assurance could be enhanced upon the use of the DICOM header of DICOM protocol based image storage. These Digital Information and Communication in Medicine (DICOM) protocols, together with secure web based file transfer - now often referred to as 'cloud' computing - have been used by Imagelabonline in academic and pharmaceutical studies since 2003.

Regardless of imaging modality, the FDA approved DICOM protcols for secure file transfer, storage and backup became the workflow backbone of Imagelabonline & Cardiovascular.

Cardiac studies

in the late 1990's and considerable expertise was built up in left ventricular mass studies. These studies evaluated LVM in the healthy aged individual, with LVM calculated according to Devereux. Also treatment of anti-hypertensive drugs in mildly hypertensives was assessed. 

Brachial endothelial function

In addition to the carotid ultrasound studies, which focus on long term disease risk and evaluate efficacy of cardiovascular agents in large populations, the functionality of the vascular endothelium can be assessed non-invasively by means of ultrasound brachial artery lumen diameter measurements. To test endothelial function the brachial artery is temporarily occluded for five minutes by inflating a blood pressure cuff above systolic pressure around the lower arm. Upon cuff release blood flow greatly increases. The increase in blood flow increases the shear stress along the vascular endothelium causing the endothelium to increasingly release nitric oxide (NO). NO is the strongest endogenous vasodilator and defuses from the endothelium into the muscularis of the arterial wall, causing the the brachial artery to dilate. The extent of dilatation caused by the increased flow is directly related to the health of the endothelium and is therefore called flow mediated dilatation or 'FMD', where FMD is defined as the maximal relative increase in brachial lumen diameter after cuff release divided by the diameter before cuff occlusion (expressed as a %). The brachial model was chosen as the method of choice for EF because in the artery atherosclerosis is virtually non-existent and the artery is close enough to the skin surface to be insonated at high resolution. 

In practice, EF testing is challenging as the arterial diameter and the flow mediated diameter change are small (in case of an arterial lumen diameter of 3mm and an FMD of 10%, 0.3mm). To be used as a tool in clinical followup studies the technology and craftsmanship is challenged even further as FMD percentages between groups and/or between groups over time are compared. To meet these challenges, together with its investigational and sponsoring partners, Imagelabonline innovated peripherals and ultrasound technology. 

Eric de Groot, MD PhD, Imagelabonline & Cardiovascular, Eindhoven and Lunteren, The Netherlands, This email address is being protected from spambots. You need JavaScript enabled to view it.+31 6 2006 2662.