WO2011069525A1

WO2011069525A1 - Nanoparticle-based marking system for visualizing medical devices in different medical imaging modalities

Info

Publication number: WO2011069525A1
Application number: PCT/EP2009/008791
Authority: WO
Inventors: Paul J. A. Borm; Viorel Rusu
Original assignee: Magnamedics Gmbh
Priority date: 2009-12-09
Filing date: 2009-12-09
Publication date: 2011-06-16

Abstract

The present invention pertains to a marking system for medical devices and to medical devices which become visible in different medical imaging modalities, wherein the marking system consists of at least one marking element (5, 6) and comprises radiopaque nanoparticles and paramagnetic particles.

Description

Nanoparticle-based Marking System for Visualizing Medical Devices in different Medical Imaging Modalities

The present invention relates to magnetic resonance imaging and X-ray fluoroscopic imaging of medical devices. The present invention concerns a marking system for medical devices; more particularly a marking system that visualizes medical devices which are provided with said marking system in different medical imaging modalities, especially in X-ray fluoroscopic imaging and in magnetic resonance imaging (MRI).

Medical imaging techniques such as X-ray fluoroscopic imaging, computer tomography (CT), magnetic resonance imaging and positron emission tomography (PET) are among the most important and versatile methods which are used by physicians today for diagnostic purposes. Beyond that, physicians also use medical imaging techniques in visualizing the guidance and placement of medical devices such as guidewires, catheters, stents, biopsy needles or the like within a patient's body. For example, X-ray fluoroscopy is the preferred imaging modality for cardiovascular interventional procedures because of its temporal and spatial resolution. However, X-ray fluoroscopy has some drawbacks such as the patient's exposure to ionizing radiation.

MRI is a medical imaging modality which does not use ionizing radiation and has the potential to supplant X-ray fluoroscopy. Moreover, MRI has greater soft tissue contrast than X-ray based imaging techniques. Beyond mere diagnostic purposes, interventional magnetic resonance (iMR) angiography as well as stent placements under MRI have been performed to demonstrate feasibility of MRI.

X-ray fluoroscopy is an imaging modality which utilizes ionizing X-ray radiation. Visualization and tracking of medical devices under X-ray fluoroscopy is accomplished either by the devices inherent absorption of X-rays or by securing radiopaque markers to the medical device. Radiopaque material absorbes X- rays and thereby creates contrast within the image, and thus is visible.

In MRI, the detection of atomic nuclei utilizes magnetic fields and radio- frequency radiation rather than ionizing radiation. Signal intensity is determined by longitudinal relaxation time (T1), transverse relaxation time (T2), proton density and flow. MRIs provide a distribution map of protons and their properties in organs and tissues. MRI contrast agents usually shorten either the T1 relaxation time or the T2 relaxation time. Suitable ions for MRI contrast agents are for example chromium(lll), manganese(ll), iron(ll), iron(lll), cobalt(ll), nickel(ll), copper(ll), praseodymium(lll), neodymium(lll), samarium(lll), ytterbium(lll), gadolinium(lll), terbium(lll), dysprosium(lll), holmium(lll) and erbium(lll). Devices to be used in MRI shall not comprise an electrically conductive element, because if the conductive element has the right shape and/or size, it may serve as an antenna for the radio frequency signal used in MRI. The energy disproportionately collected in the conductive element may inadvertently be converted to heat. Therefore, plastic devices are used in MRI. However, plastic devices poorly show-up in MRI, because the signals from the protons in polymers are broad and chemically shifted from protons in water from which the majority of MRI signal is derived.

There is a need for medical devices which can conveniently be used in X-ray fluoroscopy as well as in MRI such that these devices are visible in multi-modal imaging. Visualization of medical devices will allow tracking of the medical devices in the patient's body. Therefore, it is necessary to provide medical devices with a marking system that allows visualization of the medical device in X-ray fluoroscopy as well as in MRI.

Document WO 2005/089664 A1 teaches marker that are visible under magnetic resonance imaging and fluoroscopy, wherein a fluoroscopic imaging enhancement material and an MRI enhancement material are present in separate layers of a multi-layered marker element. This document also discloses medical devices which are provided with such a multi-layered marker. One such medical device is a balloon catheter.

In an aspect, the present invention concerns a marking system for medical devices such that the medical devices become visible in X-ray fluoroscopy and MRI, wherein the marking system comprises radiopaque nanoparticles and paramagnetic particles, and consists of one or more marking elements.

In an aspect, the present invention concerns methods for manufacturing a marking system for medical devices, wherein the marking system comprises radiopaque nanoparticles and paramagnetic particles, and consists of one or more marking elements, such that the medical devices become visible in X-ray fluoroscopy and MRI.

In an aspect, the present invention concerns the use of a marking system comprising radiopaque nanoparticles and paramagnetic particles, and consisting of one or more marking elements for visualizing and tracking a medical device which is provided with the marking system in X-ray fluoroscopy and MRI.

In a further aspect, the present invention concerns medical devices which are provided with a marking system comprising a combination of radiopaque nanoparticles and paramagnetic particles to render said medical device visible in X-ray fluoroscopic imaging as well as in MRI.

In a further aspect, the present invention concerns methods of manufacturing medical devices which are visible in X-ray fluorography and MRI, wherein said medical devices are provided with a marking system consisting of at least one marking element and comprising radiopaque nanoparticles and paramagnetic particles. In a further aspect, the present invention concerns the use of medical devices provided with the marking system consisting of at least one marking element and comprising radiopaque nanoparticles and paramagnetic particles for visualizing and tracking the medical device in a patient's body by X-ray fluoroscopy and/or MRI.

The marking system of the present invention comprises a combination of radiopaque nanoparticles and paramagnetic particles.

Radiopaqe nanoparticles are nanoparticles which absorb X-rays and thereby cause a contrast in X-ray fluoroscopic images. Suitable materials for radiopaque nanoparticles include for example gold, platinum, tungsten, tantalum, rhenium, bismuth, silver, iridium and nitrinol. Hence, radiopaque nanoparticles for the marking system of the present invention may consist of any one of the materials or mixtures thereof.

Paramagnetic particles comprise a paramagnetic material. Paramagnetic material possesses magnetism only in the presence of an externally applied magnetic field and do not retain any magnetization in the absence of an externally applied magnetic field. However, paramagnetic materials are attracted to magnetic fields and hence have a relative magnetic permeability of greater than one, i. e. a positive magnetic susceptibility.

Paramagnetic particles of the marking system of the present invention may consist of a paramagnetic material that is selected from the group comprising gadolinium, dysprosium, terbium, and alloys and oxides thereof. The term "paramagnetic particles" also included paramagnetic nanoparticles. Paramagnetic nanoparticles may consist of a paramagnetic material selected from the group comprising nickel, iron, magnesium, cobalt, and alloys and oxides thereof. Preferred paramagnetic material of paramagnetic nanoparticles are selected from the group of iron oxides. Suitable paramagnetic iron oxides include FeO, Fe₂0₃, Fe30₄. The paramagnetic particles may also consist of mixed iron oxides or mixtures of different iron oxides. The marking system of the present invention consists of one or more marking elements, wherein the marking elements comprise the radiopaque nanoparticles and/or paramagnetic nanoparticles.

In the preferred embodiment, the marking system consists of one or more marking elements, wherein the marking element, at least one of the marking elements or all the marking elements of the marking system contain radiopaque nanoparticles and paramagnetic particles. These marking elements are designated multi-functional marking elements, because they provide visualization in both X-ray fluoroscopy and MRI.

In multi-functional marking elements it is preferred that the amount of paramagnetic particles is equal to or greater than the amount of radiopaque nanoparticles within the same marking element. In another embodiment of the marking systemof the present invention, the radiopaque nanoparticles and the paramagnetic particles are present in separate marking elements. Thus, the marking system comprises two types of marking elements. The first type of marking elements contains radiopaque nanoparticles but no paramagnetic particles whereas the second type of marking elements contains the paramagnetic particles.

In specific embodiments of the present invention, the marking system consists of a combination of at least one multi-functional marking element with at least one marking element containing the radiopaque nanoparticles and at least one marking element containing the paramagnetic nanoparticles.

The marking elements may comprise a polymeric matrix wherein the radiopaque nanoparticles and/or paramagnetic particles are embedded. The polymer of the polymer matrix may be an elastomer and/or an organogel. The polymer of the polymer matrix be selected from the group of polymers comprising polyethylene, polyesters, polyamides, polyurethanes, Pebax, Arnitel, Hytrel, polypropylene, polyolefines and polyimides.

The marking elements may be present in form of solid bars, rods or disks. The marking elements may be present in form of bands or rings or in form of deposits on a medical device or within pockets which are present in the medical device. The marking elements may have a generally annular shape or a generally linear shape.

The marking system of the present invention may be manufactured in that the marking elements are formed by adding a suitable amount of radiopaque nanoparticles and/or a suitable amount of paramagnetic particles to a solution, dispersion or melt of a polymer, casting into a mould or extruding the resultant mixture, and letting the solidify in that it may cool down or in that the solvent is removed by drying. The prefabricated marking elements may then be secured to the medical device or secured to components of the medical device during the devices manufacturing such that the marking elements become incorporated into the medical device.

Medical devices which are provided with a marking system of the present invention become visible in X-ray fluoroscopy and MRI. Thus, the present invention comprises the use of the marking system for visualizing and tracking medical devices, in particular of medical devices otherwise not visible in X-ray fluoroscopy and MRI, in these medical imaging modalities.

The marking system of the present invention is incorporated into or secured to a medical device, preferably a medical device formed of a polymer body. Therefore, the present invention also comprises medical devices which are provided with the marking system of the present invention. Preferred medical device to be provided with the marking system of the present invention are catheters, in particular balloon catheters, guidewires, stents, biopsy needles or coils.

The medical devices may be provided with the marking system of the present invention in that prefabricated marking elements are secured to the medical device. It is also possible to secure the marking element(s) or a portion of the marking element to components of the medicinal device during the devices manufacturing such that these marking elements may become incorporated into the medical device.

In a preferred method of manufacturing medical devices which are visible in in X-ray fluoroscopy and MRI, the medical device or a component of the medical device is coated, at least in a portion of said device or component, with a polymer solution or polymer dispersion which further contain radiopaque nanoparticles and/or paramagnetic particles.

The medical devices which are provided with the marking system of the present invention can be used in X-ray fluoroscopy and/or MRI. These medical devices are visualised in X-ray fluoroscopy and MRI due to their labelling with the marking system, and can easily be tracked when introduced into a patient's body.

The present invention is explained in more detail herein below with reference to the figures. The figures are for illustrative purposed only and are not construed to restrict the present invention to the specific embodiments shown in the drawings or in any other way.

Fig. 1A is a side view of the tip of a guide wire comprising different marking elements located at the core of the guide wire.

Fig. 1 B is a side view of the tip of a guide wire comprising different marking elements, wherein a first marking element is located at the core of the guide wire and a second marking element is encapsulated in the sheath of the guide wire. Fig. 1C s a side view of the tip of a guide wire comprising different marking elements, wherein a first marking element is located at the core of the guide wire and a second marking element is secured to the sheath of the guide wire.

Fig. 2A is a side view of the tip of a guide wire comprising a multi-functional marking element that is secured to the core of the guide wire.

Fig. 2B is a side view of the tip of a guide wire comprising a multi-functional marking element that is encapsulated in the sheath of the guide wire.

Fig. 2C is a side view of the tip of a guide wire comprising a multi-functional marking element that is secured to the sheath of the guide wire.

Referring to Figs 1A to 1C showing the distal end of a guidewire 1 , the guidewire 1 comprises a core 2 and a sheath 3. The guidewire further comprises a hydrophilic coating 4. The guidewire further includes two types of marking elements, a first marking element 5 and a second marking element 6, wherein the first marking element 5 contains radiopaque nanoparticles. The second marking element 6 contains paramagnetic particles. It is to be understood that in a different embodiment, the marking element 5 may contain the paramagnetic particles whereas the marking element 6 contains the radiopaque nanoparticles. The marking elements are positioned along the longitudinal axis of the guide wire.

The marking elements of the two types may be secured to the core 2 of the guidewire 1 (Fig. 1A). Instead of being secured to the core 2, the marking element 6 may also be encapsulated within the sheath 3 of the guidewire 1 (Fig. 1 B) or secured to the sheath 3 of the guidewire 1 (Fig. 1C). It is understood that the other type of marking element 5 may also be encapsulated within the sheath 3 or secured to the sheath 3 instead of being secured to the core 2 of the guidewire 1.

Referring to Figs. 2A to 2C showing the disiai end of a guidewire i , the guidewire 1 comprises a core 2 and a sheath 3. The guidewire further comprises a hydrophilic coating 4. The guidewires further comprise a multi- functional marking element 7 which comprises radiopaque nanoparticles as well as paramagnetic particles. The multi-functional marking element 7 that may either be secured to the core 2 of the guidewire 1 (Fig. 2A), encapsulated into the sheath 3 of the guidewire 1 (Fig. 2B), or secured to the sheath 3 of the guidewire 1.

Claims

1. A marking system for visualising a medical device in X-ray fluorography and MRI, the marking system comprising

- radiopaque nanoparticles, and

- paramagnetic particles.

2. The marking system according to claim 1 , characterised in that the radiopaque nanoparticles consist of a material which is selected from the group comprising gold, platinum, tungsten, tantalum, rhenium, bismuth, silver, iridium, and complexes, and mixtures thereof.

3. The marking system according to claim 1 or 2, characterised in that the paramagnetic particles are paramagnetic nanoparticles.

4. The marking system according to any one of the preceding claims, characterised in that the paramagnetic particles consist of a material that is selected from the group comprising gadolinium, dysprosium, terbium, and alloys and oxides thereof.

5. The marking system according to claim 3, characterised in that the paramagnetic nanoparticles consist of a material that is selected from the group comprising nickel, iron, magnesium, cobalt, and alloys and oxides thereof, with iron oxide being preferred.

6. The marking system according to any one of the preceding claims, characterised in that the marking system consists of one or more marking elements.

7. The marking system according to claim 6, characterised in that the radiopaque nanoparticles and the paramagnetic particles are present in different marking elements.

8. The marking system according to claim 6, characterised in that the radiopaque nanoparticles and the paramagnetic particles are present in the same marking element(s).

9. The marking system according to any one of the preceding claims, characterised in that the marking elements comprise a polymeric matrix containing the radiopaque nanoparticles and/or paramagnetic particles.

10. The marking system according to claim 9, characterised in that the polymer of the polymeric matrix is selected from the group comprising polyethylene, polyesters, polyamides, polyurethanes, Pebax, Arnitel, Hytrel, polypropylene, polyolefines and polyimides.

11. The marking system according to any one of the preceding claims, characterised in that the marking elements are present in form of layers, rings, strips, stripes, bars, rods or discs.

12. A method of manufacturing a marking system according to any one of the preceding claims, characterised by the steps of

- adding radiopaque nanoparticles and/or paramagnetic nanoparticles to a solution, dispersion or melt of a polymer,

- casting into a mould or extruding the mixture of polymer with radiopaque nanoparticles and/or paramagnetic nanoparticles, and

- solidifying the moulded or extruded mixture.

13. Use of the marking system according to any one of claims 1 to X for visualising and tracking medical devices in X-ray fluorography and/or MRI.

14. A medical device comprising a biocompatible body and a marking system, the marking system comprising a fluoroscopic imaging enhancement material and an MRI enhancement material, characterised in that the fluoroscopic imaging enhancement material is selected from the group of radiopaque nanoparticles, and in that the MRI enhancement material is selected from the group of paramagnetic particles.

15. The medical device according to claim 14, characterised in that the biocompatible body is a polymeric body.

16. The medical device according to claim 14 or 15, characterised in that the medical device is selected from the group comprising guidewires, catheters, balloon catheters, coils and biopsy needles.

17. A method for visualising a medical device in X-ray fluoroscopy and MRI, characterised in that the medical device is provided with a marking system according to any one of claims 1 to 11 , characterised in that the marking element(s) is/are secured to the body of the device or to components of the device.

18. Use of a medical device according to any one of claims 14 to 16 in X-ray fluoroscopy and/or MRI.