WO1998034564A1

WO1998034564A1 - Medical ultrasound apparatus

Info

Publication number: WO1998034564A1
Application number: PCT/GB1998/000241
Authority: WO
Inventors: Robert Julian Dickinson
Original assignee: Intravascular Research Limited
Priority date: 1997-02-08
Filing date: 1998-02-05
Publication date: 1998-08-13
Also published as: GB2321853A; GB9702612D0

Abstract

In order to overcome the problem of tissue proliferation around a coronary stent, the stent is provided with means by which it can be made to radiate ultrasonic energy when in an operative position.

Description

MEDICAL ULTRASOUND APPARATUS

The present invention relates to medical ultrasound apparatus and more particularly to the use of so-called stents in the treatment of vascular disorders.

Coronary artery disease is a significant cause of death in the Western World, and a number of methods of treatment have been developed. Surgical treatment in which a vein is grafted to replace the diseased artery, known as coronary artery bypass grafts, are successful, but require the trauma of major surgery with its concomitant risks and long recovery periods, and is limited to a selected patient population.

In more recent years cardiac catheters have been increasingly used to treat the narrowing of coronary arteries, using angioplasty balloons to widen the lumen. The lumen widening in many cases is temporary and the vessel relaxes back to its original narrow lumen.

An improved treatment involves implanting metallic stents which act to hinder the remodelling of the opened vessel. A stent is essentially an elongated metallic device which can be introduced into the target area and expanded to as it were shore up the collapsed or partially collapsed arterial wall defining the lumen. A typical method of delivery employs a balloon catheter with the stent carried around the outside of the deflated balloon so that when the balloon is then inflated (at the target area) the stent is caused to expand into its operative position.

Stents do provide a longer lasting treatment for coronary artery stenosis than percutaneous coronary transluminal angioplasty (known as PCTA) but further narrowing or re-stenosis has been observed. The mechanism for this can be the formation of a thrombus around the stent, although this can be minimised by improved stent placement and appropriate use of anti-coagulation therapy. A further mechanism is a longer term proliferation around the foreign body of the stent, termed neo-intimal tissue proliferation.

A new method to reduce this tissue proliferation utilises the well known fact that ionising radiation has greater cytotoxicity on rapidly growing cells and involves radiating the coronary region, either with external radiation or via an intraluminal radiation source implanted into the coronary artery. A further technique provides the radiation to the tissue by implanting stents which are radioactive. However the use of radioactive materials has significant radiation protection implications for clinical and nursing staff, the patient and the general population, and it may be expected that these may hinder this method being more rapidly adopted.

The present invention is concerned with reducing or eliminating this problem of tissue proliferation around a coronary stent.

According to the present invention a stent is provided with means by which it can be made to radiate ultrasonic energy when in an operative position.

The principle behind the invention is to use the stent to radiate ultrasonic energy into the surrounding tissue. It is known that ultrasonic energy can affect the growth of tissue and at certain intensities is cytotoxic. The advantage of ultrasound radiation is that it is non-ionising and does not couple well to air, so there are no radiation protection issues.

Because of the small size of the stent it is very difficult to provide it with its own internal power source. Therefore the energy is coupled from outside the body via electromagnetic radiation. External coils are excited to produce a radio frequency magnetic field in the coronary area. This couples to the implanted stent and the magnetic field generates an oscillating strain in the metal stent structure, the consequent vibration couples into the tissue in contact with the stent.

The choice of frequency is limited by lower and upper bounds. The frequency has to be higher than the frequencies at which any induced currents can trigger muscle movement, typically 100kHz. At the upper end the frequency must be less than 30-40 MHz for the magnetic fields to penetrate to the coronary artery region.

The present invention is also concerned with using the ultrasound vibrations of the stent to improve the performance of drugs. These drugs are typically either anti-thrombolytic agents, or cytotoxic agents that prevent neo-intimal tissue proliferation.

How the invention may be carried out will now be described by way of example only and with reference to the accompanying drawings in which:

Figure 1 is a perspective diagrammatic view of the overall arrangement of the present invention; Figure 2 is a perspective diagrammatic view of one construction of stent to which the present invention may be applied in the arrangement shown in Figure 1 ;

Figure 3 is a perspective diagrammatic view of a second construction of stent to which the present invention may be applied in the arrangement shown in Figure 1.

Figure 4 is a perspective diagrammatic view of a third construction of stent which may be applied in the arrangement shown in Figure 1.

Figure 5 illustrates one external arrangement for generating the magnetic field for energising the stent positioned within the patient;

Figure 6 is a view similar to Figure 5 showing a second external coil arrangement.

Figure 1 illustrates the general arrangement involved in applying the present invention.

A patient 1 is supported in a horizontal position by a known arrangement (not shown).

A metal stent 2 has been inserted into the patient so that the operative part of the stent is located in the appropriate target area within the patient, typically within one of the patients arteries.

A pair of electrical coils 3 and 4 are positioned as indicated so that the patient 1 lies substantially on the common axis X-Y of the two coils 3 and 4. The stent for use with the present invention can take a number of forms depending on the energisation frequency being used.

Three examples of constructions of stent which could be used by the present invention are shown in Figures 2, 3 and 4.

The stent 2 of Figure 2 comprises a closed coil having a plurality of windings 5 and a return portion 6 joining the two ends of the coil. The windings 5 and portion 6 are electrically insulated from one another preferably by the windings carrying an insulating layer or coating (not shown). Means may be provided to enable the coil to operate as a resonant circuit, e.g. by the incorporation of a capacitor, in order to increase the effectiveness of the coil.

Figure 3 illustrates a second possible construction in which the stent 2 comprises essentially a tubular member 7 having a plurality of slots 8, the tube 7 being made from a material which is magneto-strictive. Examples of appropriate magneto-strictive materials are nickel and stainless steel.

A third example of a possible construction is shown in Figure 4 in which again the stent 2 is of generally cylindrical configuration but each of the conductive paths of the stent comprises metal portions 9 interrupted or separated by insulation portions 10. In other words the stent is of a laminated construction. The insulation portions 10 could be in a number of configurations including helical (as illustrated), mutually parallel and extending longitudinally of the cylindrical surface or even axially spaced apart mutually parallel rings along the length of the cylinder The stent design shown in Figure 2 is suitable for operation at low frequencies.

With this construction, as indicated earlier, there is a closed coil configuration. When this stent is energised, by means of the coils 3 and 4, shown in Figure 1 , currents will be induced in the coils of the stent by means of mutual inductance which in turn will generate an electromotive force in the coil windings. The frequency of the induced force is limited to the self resonant frequency of the windings 5 of the stent.

If higher frequencies of energisation are required then the stent shown in Figure 3 is more suitable. As indicated earlier the stent 2 of Figure 3 is made of a magnetostrictive material, such as nickel or stainless steel, which will change its dimensions when energised, such that the ultrasound generated is twice that imposed by the external coils 3 and 4. Thus for input of 20 MHZ an output of 40 MHZ can be achieved. However with this construction the operating frequency is limited by the reduction in magnetic field caused by eddy currents in the metal forming the cylinder 7.

In order to overcome this limitation a stent could be constructed as indicated in Figure 4. The construction of the stent in Figure 4 is more complicated than that of either Figure 2 or Figure 3 in that it is essentially a laminated structure having both conducting materials and insulating materials 9 and 10 respectively as described earlier. As far as the energisation arrangement shown diagramatically in Figure 1 is concerned a number of other arrangements of energisation coils could be employed, two of these being shown in Figures 5 and 6 respectively.

In the arrangement of Figure 5 the radio frequency magnetic field is generated by two coils 1 1 and 12 which are substantially circular but positioned in a horizontal orientation above and below the patient 1, in contrast to the arrangement shown in Figure 1 in which the two coils 3 and 4 lie in substantially vertical planes, the patient lying along the common axis X-Y.

In the arrangement of Figure 5 the coils 1 1 and 12 are again on the same axis but in this arrangement the axis is normal to the axis in which the patient 1 is lying.

The coils 1 1 and 12 are energised by a radio frequency generator 13.

In the arrangement of Figure 6 there are three radio frequency energisation Helmholtz coils 14, 15 and 16 which are positioned as indicated in relation to patient 1 in order to generate fields in the X, Y and Z directions respectively. In particular the z coil 15 has an axis which lies substantially along the axis along which the patient 1 is lying (as with the coils of Figure 1) the x coil 14 lies substantially horizontally above the patients and the y coil 16 is positioned substantially vertically alongside the patient.

The three coils 14, 15 and 16, set on the three perpendicular axis x, y and z, allow the magnetic field vector to be controlled by sending the ratios of the currents in the coil pairs to be equal to the Cartesian components of the field vector. The coils 14, 15 and 16 are driven by three independent radio frequency generators 17, 18 and 19 respectively which are controlled by a controller 20 so that the amplitude of each generator 17, 18 and 19 is adjusted according to the desired direction of the magnetic field. The coils 14, 15 and 16 could be Helmholtz coils but this is not essential because obtaining an even field is not critical. In fact it may be advantageous to arrange the coils so that the field is concentrated at the position of the stent 2.

Although multi coil arrangements have been described and illustrated, for energising the stent 2, the invention is possible using only one energisation coil. The way in which the arrangement according to the present invention is used will now be briefly described.

In order to prevent or minimise the unwanted tissue proliferation around the coronary stent referred to earlier the stent 2, which is already embedded in the patient and is not intended to be removed, would be energised on a series of occasions in order to prevent the unwanted condition from occurring.

Because this energisation only involves placing an energisation coil or coils outside the patient, the treatment of the patient, in a series of regular doses as indicated earlier, can be carried out as an outpatient procedure.

Variations may be made to both the detailed design of the stent and to the coil arrangement for energising it from outside the patient, within the scope of the following claims. As indicated earlier the present invention also relates to employing the vibrating stent just described to improve the performance of drugs which are typically either anti-thrombolytic agents, or cytotoxic agents that prevent neo-intimal tissue proliferation.

There are a number of ways these drugs can be administered in combination with the vibrating stent three of which are described below:

Method

Systemically by intra-arterial injection as discussed in US patent 5509896.

Method 2

Systemically by intra-arterial injection, with ultrasound contrast agents which increase the effect of the ultrasound, as disclosed in US patent 538041 1.

Method 3

Encapsulated in micro-bubbles which are then systemically administered. It is known that ultrasound can burst these bubbles to release its contents ('Ultrasound

Contrast Agents', Ed. B. B. Goldberg, published by John Dean Press 1996). The use of micro-bubbles to carry therapeutic agents with external ultrasound to burst them is disclosed in US patents 5580575 and 5558092, as a coating to the stent, either as encapsulated micro-bubbles or as a chemical coating.

Methods 1 and 2 have the advantage that the effect of the anti-thrombylitic agents is locally enhanced around the stent area, thus increasing the effect without the need to increase the overall systemic dose. This differential between local dose and systemic effect is further increased in Method 3, where the drug is only activated where it is released from the micro-spheres, and so the systemic effect is smaller. Method 4 has the advantage that the effect of the drug is even further localised to the neighbourhood of the stent. Unlike using standard coated stents the application of the drug can be activated at a time independent of the stent development. Hence the time-profile of the application of the drug can be tailored to suit the development of thrombus formation or tissue formation.

Claims

1. A stent provided with means by which it can be made to radiate ultrasonic energy when in an operative position.

2. A stent as claimed in claim 1 in which the operative part of the stent comprises a helical elongated coil having its opposite ends interconnected.

3. A stent as claimed in claim 1 in which the operative part of the stent comprises a metallic cylinder provided with a pattern of apertures.

4. A stent as claimed in claim 1 or 3 made from a magnetostrictive material.

5. A stent as claimed in of claim 1 in which the operative part of the stent is made up of a laminated structure comprising metallic segments alternating with insulation segments.

6. A stent substantially as hereinbefore described with reference to and as shown in any one of Figures 2,3 or 4 of the accompanying drawings.

7. A stent as claimed in any of claims 1 to 6 in which the stent is coated with a drug.

8. A stent as claimed in claim 7 in which the drug is encapsulated in a mirror-sphere.

9. Apparatus for use with a stent as claimed in any previous claim which comprises an energisation coil arrangement substantially as hereinbefore described with reference to and as shown in any one of Figures 1 , 5 and 6 of the accompanying drawings and adapted to be located externally of a patient in which the stent is embedded.

10. A method of operating a stent which comprises inserting the stent into its operating position and then energising it by means of a magnetic coil arrangement external of and separate from the stent to cause the stent to emit ultrasonic energy.

1 1. A method of operating a stent as claimed in claim 10 which method includes the step of administering a drug systemically either with ultrasound contrast mirror-bubbles or with micro spheres containing the drug.

12. A method of operating a stent substantially as hereinbefore described with reference to and as shown in the accompanying drawings.