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10.1 INTRODUCTION

Blood flow measurements in individual vessels have a number of important clinical and research applications but previous techniques have serious clinical limitations or inaccuracies.

X-ray angiography remains the vascular imaging modality which gives the highest spatial and temporal resolution and is widely used in clinical practice to obtain high-quality vessel images. The ability to derive quantitative flow data from this procedure would be a useful clinical tool.

A novel technique has been developed for the quantitative measurement of pulsatile blood flow waveforms and mean blood flow rates using digital X-ray angiographic data.

Blood flow waveforms were determined following an intra-arterial injection of contrast material. The first stage in data reduction was to generate a ‘parametric image’ from dynamic X-ray angiographic images in which the image grey-level represented contrast material concentration as a function of time and distance along a vessel segment.

Adjacent concentration-distance profiles in the parametric image of iodine concentration versus distance and time were shifted along the vessel axis until a match occurred. A match was defined as the point where the mean sum of the squares of the differences between the two profiles was a minimum. The distance translated per frame interval gave the instantaneous contrast material bolus velocity.

A 3D reconstruction technique for locating the 3D path length of a blood vessel from biplanar angiograms that had been implemented by our group was validated. The use of a perspex calibration cube for the geometric calibration of

the X-ray gantry orientation allows satisfactory reconstruction of the 3D course of the vessel centre line ‘in-vivo’, and has been validated in phantom studies. The 3D location of the blood vessel centre line permits the computation of the radiographic magnification, the angle between vessel axis and the X-ray beam, and the true vessel path length.

For measurements of vessel cross-sectional area a densitometric method was used. The technique is based on image densitometry in which the integral of the image intensity is computed along a profile perpendicular to the projection of the vessel axis. The true cross-section is related to the densitometric measure. The X-ray magnification factor and angle between the vessel axis and the X-ray axis were used in the calculation. This technique was validated using 3D reconstruction of a phantom simulating vascular structures. The blood velocity waveform estimates were converted into volume flow waveforms by multiplying by this computed vessel cross sectional area.

Initially our algorithm for computing velocity was assessed using simulated angiographic data as this allowed greater flexibility in designing suitable experiments, more control of experiments, and less cost in capital equipment and material. In addition, it was of interest to predict the X-ray quantum limited precision of the technique, for a wide range of blood vessel calibres and blood flows, with data that was free from non-random errors and artefacts. Quantitative comparison with other algorithms was also made using these computer generated images. A total of 114 different experiments were simulated for a range of calibres and flow rates using a computer model. When used to measure the blood flow waveform using our velocity algorithm, there was excellent agreement between the input flow waveforms and those determined by our radiographic technique, with both laminar flow and constant axial flow (‘plug’ flow) patterns. In addition our algorithm for computing velocity produced results which were independent of the injection techniques used.

Further validation of our technique computing pulsatile flow was carried out using an experimental model of blood circulation. A phantom haemodynamic circulation was designed and constructed, it consisted of a pump, flexible plastic tubing, the tubular probe of an EMF and a solenoid valve to allow simulation of pulsatile flow

waveforms including reverse flow. Small boluses of contrast material were injected at various positions in the circuit. Phantom studies were used to compare simultaneous measurements of blood flow using X-ray angiographic data with measurements using an EMF. A range of blood flow rates and plastic tube diameters was used. The validation of our technique was performed on 2D digital X-ray projections and also using 3D reconstruction from biplanar X-ray projections. The validation was repeated (1) for a range of distances between the injection and flow analysis measurement sites and (2) for various lengths of vessel analysed.

The results from physical flow model experiments have demonstrated that accurate instantaneous and mean volume blood flow is possible in phantoms that provide an approximation of the situation ‘in-vivo’.

In order to demonstrate the applicability of the flow technique in clinical practice, parametric images were generated from clinical dynamic X-ray angiographic data and flows were computed in the femoral and cerebral arteries. Although satisfactory results were obtained from clinical data several problems were encountered:

(1) Artefact due to overlapping blood vessels. This was dealt with by modification of our algorithm for computation of velocity to exclude regions containing data from overlapping blood vessels (see chapter 6).

(2) Patient motion. This could cause severe artefacts in the parametric images which in turn led to inaccuracies in the computed flow.

10.2 ADVANTAGES OF OUR ANGIOGRAPHIC FLOW TECHNIQUE

The main advantages of our flow technique are that:

(1) Accurate instantaneous flow information is provided.

(2) It permits the determination of average flow under highly pulsatile conditions.

(3) The method is relatively insensitive to slow blood vessel motion during the imaging procedure (as the analysis is performed on two consecutive

frames, any vessel motion that is slow relative to one frame duration (0.04 sec)) can, in principle, be accounted for.

(4) The method will provide useful flow data with comparatively small amounts of contrast medium.

(5) It is insensitive to the precise injection technique.

(6) It appears to be relatively insensitive to the distance between the injection site and blood flow measurement site.

(7) This technique is no more invasive or inconvenient than the standard DSA procedure. The high framing rate used in this study can easily be reformatted to give the framing rate of about 2 frames/sec used in routine angiography and as such would deliver no extra total radiation dose to the patient or total contrast load.

10.3 LIMITATIONS OF OUR ANGIOGRAPHIC FLOW TECHNIQUE

Although the proposed digital X-ray angiographic technique for pulsatile flow measurements can compute accurate velocity waveforms from distance-density curves for a wide range of flow velocities, there are limitations to this technique.

(1) High blood velocities. The technique becomes inaccurate at very high velocities. This is due to the limited length of artery that can be analysed. This limits the maximum velocity that can be detected by our algorithm. In the comparison of two distance-density curves, some of the same portions of the bolus must appear in the two profiles. This is entirely dependent on the frame rate acquisition and length of vessel imaged; the frame rate must be high enough so that a portion of the bolus imaged in one frame appears in the subsequent frame.

(2) Misregistration artefacts. One of the inherent limitations of temporal subtraction DSA is the susceptibility of this technique to misregistration artefacts resulting from either voluntary movement (breathing and displacement of the extremities), or involuntary movement (peristalsis, cardiac motion, swallowing, and arterial pulsations). The misregistration artefacts result in an artefactual signal that cannot be separated from the true iodine signal. This could be overcome by using unsubtracted X-ray angiographic images for the quantification of volume blood flow. The

primary disadvantage of the unsubtracted images is the presence of overlying tissue signals, which will vary unpredictably along the vessel profile. Therefore our initial clinical efforts have been concentrated on parts of the body which are less prone to patient movement and hence, the technique has been applied to the femoral arteries and the vessels of the head and neck.

(3) Scattered radiation. The contribution of scattered X-ray radiation is difficult to correct because the distribution and quantity of scattering is not expected to be uniform. The light intensity at each location of the intensifier output image is made up of two components. One is dependent on the degree of X-ray absorption while the other is an additional quantity dependent on scattering from other parts of the body. The latter portion is not only dependent on the site of sampling (centre or border of the image) and the distribution of brightness across the image, but may change with temporal variations in brightness (e.g., the presence of contrast material in vascular structures adjacent to the site of measurement). Inaccuracies of this kind may be overcome in the future by the application of algorithms that provide simulation of scattering for each individual angiographic image.

(4) Injection of Contrast Material. In order that the velocity information may be extracted from the movement of a contrast bolus, there must be a contrast material concentration gradient along the vessel. Also we have shown that our velocity algorithm is independent of injection technique (see chapter 7) but injection of a large volume can perturb the flow substantially. We used an automatic injector for extremely precise control over the volume and flow rate of injection.

In addition, the effects of the process of introducing a catheter into a blood vessel, the continuing presence of the catheter, the disturbing influence of the injection, the volumetric, viscous and inertial consequences of having introduced a foreign fluid, and the pharmacological effects of contrast material must all be considered as possible sources of error in flow estimates.