Over the past two decades, there has been an effort at several synchrotron facilities to develop the technology of transvenous synchrotron coronary angiography [1]. The first patient studies have now been carried out at ID17, the Medical Beamline [2]. The programme addresses the fundamental concerns associated with conventional angiography, which requires the injection of a contrast agent directly into the coronary arteries by means of arterial catheterisation. The potential risks of patient mortality and morbidity, the discomfort and the frequent hospitalisations required prevent its use for routine screening or research. These problems will be essentially eliminated by the transvenous technique in which the contrast agent is injected into a peripheral vein. At the ESRF, the medical research facility has been commissioned for basic research studies in areas of fundamental bio-medical and pre-clinical research [3]. The commissioning of the human angiography program brings to an end the construction phase of the facility. The X-ray energies and intensity are those required for the dual-energy digital subtraction technique to enhance the image contrast of the coronary arteries following venous injection of the iodinated contrast agent. 

The X-rays available in the medical facility radiate from a wiggler magnet and are about 4 orders of magnitude more intense than from a conventional source. The ESRF monochromator is a single cylindrically bent silicon (111) crystal mounted in Laue geometry, which focuses the beam vertically. Two monochromatic beams are produced, one with an energy above and the other below the K-absorption edge of iodine at 33.17 keV. The data acquisition system is made of a high purity germanium detector associated with high dynamic range electronics (16 bits). The detector is electrically segmented into 864 strips distributed over two rows, resulting in a detection element pitch of 350 micrometres. Since the X-ray beam is fan-shaped (0.7 mm high and 150 mm wide) it is necessary to move the patient through the beam in order to obtain two-dimensional angiograms. The positioning system, which allows both for positioning of the patient and the scan motions during the data acquisition, is a high-precision stage with seven degrees of freedom. The X-ray dose received by the patient amounted to 30 mGy/image.

A research protocol has been designed to evaluate the potential of this method, in comparison with the conventional arterial catheterisation technique. Patients included in the protocol have previously undergone angioplasty. In 30% of the cases re-stenosis occurs after angioplasty. If a re-stenosis is suspected, the patient is imaged at the ESRF in orientations that allow visualisation of the right coronary artery, and within the next few days with the conventional technique at the hospital. The total radiation dose to a patient during the synchrotron imaging sequence is limited to 0.2 Gy by the medical protocol. Thirty patients are included in this validation phase, which will be completed in 2001.

The catheter is inserted into the brachial vein in the arm under fluoroscopy control. The patient is then installed in the scanning system in the imaging room. The correct orientation is first checked by taking a single image at low X-ray dose and without injection of a contrast agent. The transit time between the injection of the contrast agent and the arrival of the bolus in the heart is then measured using a series of five synchrotron images at low X-ray dose (5 mGy) and with a small amount of contrast agent (10 ml). When the contrast agent used for the transit time estimation has disappeared totally from the venous circulation, the imaging sequence takes place. 45 ml of iodine contrast agent are injected under remote control (15 ml/s). The image sequence is started a few seconds after the injection of the contrast agent depending on the transit time evaluation. Images are then acquired to follow the iodine bolus through the patient circulation while the positioning system is moving up and down.

One image obtained with the first patient at the ESRF is shown on Figure 9a. Stenosis appears visible inside the stent in the second segment C2, and a known distal stenosis visible at the crux remains mild (less than 50%). The excellent visualisation of the distal part of the right coronary artery (RCA) should be noted. These findings are in excellent agreement with the conventional selective coronary angiogram performed a few hours later in the hospital cardiology unit (Figure 9b).

Figure 9
Fig. 9: a) Intravenous synchrotron angiogram, b) Conventional angiogram.

The synchrotron method is a very efficient minimally-invasive technique to visualise and quantify coronary stenosis. The ESRF has advantages over other synchrotron facilities for this type of research. The beamline has been designed to allow imaging at the gadolinium K-absorption edge in the future. Research with a Gd contrast agent may lead to superior images with lower radiation dose to the patients, particularly for large patients. One of the major strengths of the programme is the close collaboration and support by the staff from the Centre Hospitalier Universitaire. This is essential to the long-term development and utilisation of the facility.

References
[1] R. Lewis, Phys. Med. Biol. 42, 1213-1243 (1997).
[2] H. Elleaume, S. Fiedler, F. Estève, B. Bertrand, A.M. Charvet, P. Berkvens, T. Brochard, G. Le Duc, C. Nemoz, M. Renier, P. Suortti, W. Thomlinson and J.F. Le Bas, Phys. Med. Biol. 45, L39-L43 (2000).
[3] H. Elleaume, A.M. Charvet, P. Berkvens, G. Berruyer, T. Brochard, Y. Dabin, M.C. Dominguez, A. Draperi, S. Fiedler, G. Goujon, G. Le Duc, M. Mattenet, C. Nemoz, M. Perez, M. Renier, C. Schulze, P. Spanne, P. Suortti, W. Thomlinson, F. Esteve, B. Bertrand and J.F. Le Bas, Nucl. Instr. and Meth. A428, 513-527 (1999).

Authors
H. Elleaume (a), S. Fiedler (b), F. Estève (a), B. Bertrand (a), A.M. Charvet (a), A. Bravin (b), P. Berkvens (b), G. Berruyer (b), T. Brochard (b), Y. Dabin (b), A. Draperi (b), G. Goujon (b), G. Le Duc (b), C. Nemoz (b), M. Perez (b), M. Renier (b), P. Suortti (b), W. Thomlinson (b) and J.F. Le Bas (a).
(a) Unité IRM Centre Hospitalier Universitaire, Grenoble (France)
(b) ESRF