GB2349825A

GB2349825A - Extracorporeal blood circuit for removing MRI contrast agent from blood

Info

Publication number: GB2349825A
Application number: GB9910746A
Authority: GB
Inventors: Ian Robert Young
Original assignee: Marconi Electronic Systems Ltd
Current assignee: BAE Systems Electronics Ltd
Priority date: 1999-05-11
Filing date: 1999-05-11
Publication date: 2000-11-15
Also published as: GB9910746D0

Abstract

A separator for reducing the concentration of MRI contrast agent in the blood of a heart patient comprising a pump for connection to an intravenous catheter 6 and an intra-arterial catheter 7 and a magnetic separator 8 for separating the contrast agent from the blood passing between the two catheters. According to the embodiment, insert 9 is aligned in the path of the blood flow A, aligned with magnetic field B. Blood passing through tube 10 encounters wire mesh 13 carried on spools 11 and 12 at which point the strongly magnetised contrast agent will adhere to the mesh whilst the much less paramagnetic blood constituents such as oxyhaemoglobin will pass through the mesh. Quick removal of the contrast agent allows further images to be taken for quick assessment of the effectiveness of an injected thrombolytic agent.

Description

2349825 USE OF MR1 CONTRAST AGENTS This invention relates to the use of

contrast agents for magnetic resonance imaging (MR1).

Typically, a contrast agent is injected into the vascular system of a patient, and circulates through the body in, say, half a minute. An image taken of the patient then shows enhanced features relating to the contrast agent.

In X-ray computed tomography, contrast agents contain atoms that attenuate or scatter the incident X-ray beam. This permits visualisation of the agent regardless of its location. MRI contrast agents are not visualised directly, but affect the relaxation times of the water protons in nearby tissue. For example, water within the body tumbles much faster than the Larmor frequency, resulting in a long T1 relaxation time. An MRI contrast agent is paramagnetic and therefore causes fluctuations of the local magnetic field as it tumbles. Since d-ds happens at frequencies much more closely matched to the

Larmor frequency, this fluctuation of the local field influences the relaxation times of the water protons in nearby tissue e.g. by reducing the TI relaxation time, so that the contrast of an image can be increased.

A commonly used contrast agent is gadolinium chelate. A commonly used chelate is diethylenetriarninepentaacetic acid (DPTA). Another contrast agent based on gadolinium is Gd DOTA. Very small iron oxide particles (which are super- 2 paramagnetic) are also used as a contrast agent in MR imaging.

Typically, the way in which the contrast agent would be used would be to take an image of a region of interest before a contrast agent was introduced, and then another image after the contrast agent had circulated through the body.

The problem with contrast agents is that they are excreted relatively slowly, typically over periods ranging from tens of minutes to a few days. This means that once an agent has been given, it is present through any subsequently rapidly repeated examination.

Hence, where subtle changes are being studied by detecting the presence and absence of the agent, there is only one opportunity for making the observations. This is a particular drawback when studying perfusion (flow through capillaries delivering blood to tissues), because the amount of blood flowing is very small. Further, only a small percentage, less than 5%, of tissue protons are intravascular.

is For example, in the case of a patient who has suffered a suspected thrombosis, an image of the heart may be taken before contrast agent has been injected into the patient and again after contrast agent has been given. This would then make it possible to assess whether particular areas of the heart muscle were starved of blood. However, it would be very useful to be able to assess whether a thrombolytic agent given to the patient had been successful in re-establishing blood supply or not. The effectiveness of subsequent treatment would be hard to determine because of the presence of the agent, which circulates through the vascular system, diffuses into the extra- cellular spaces of 3 all tissues with the exception of the brain, and is excreted with a half life that varies between 15-20 minutes and a few hours, depending on the agent being used. In fact the half life tends to underestimate the time until complete excretion, since some contrast agent is excreted via the kidneys, whereas the rest diffuses out of the bloodstream into normal tissue, from which it ultimately diffuses back into the bloodstream. Until enough of the agent has been removed, typically of the order of 75-80%, if not too much loss of sensitivity is not to occur, it is not possible to check by repeating the original study whether the treatment given as a result of the perfusion assessment has been successful or not. What is of greater interest in many perfusion studies is the first pass i.e. the arrival and passage of blood containing contrast agent, since this occurs when there is least contamination by agent which has perfused into them.

The invention provides a separator for reducing the concentration of MR1 contrast agent in the blood of a patient, which comprises a pump for connection to intra-arterial and intravenous catheters, and a magnetic separator for separating contrast agent from the blood passing from the intra-arterial catheter to the intravenous catheter.

Advantage is taken of the paramagnetic nature of the contrast agent to remove it from the bloodstream, which has the added advantage that there is then less time for diffusion to occur. De-oxyhaernoglobin and the degradation products of haemoglobin can also be paramagnetic, but to a much lesser extent than contrast agent, and oxyhaemoglobin is diamagnetic.

4 Ways of carrying out the invention will now be described in detail, by way of example, with reference to the accompanying drawings, in which:

Figure 1 is a plan view of magnetic resonance imaging apparatus, parts of which are shown diagrammatically; and Figure 2 is a sectional view of a part of the magnetic separator of the apparatus of Figure 1.

Referring to the figure, a patient is located in the bore 1 of a superconducting magnet 2 which is provided with the usual gradient and r. f. coils 3 which, together with the magnet 2, are responsible for generating magnetic field gradients across the patient and providing an r. f. impulse to excite protons in the patient to resonance. A receiver coil (not shown) detects the signals produced as the protons relax and return to their initial 15 state. Control means 4 is responsible for controlling pulse sequences, as well as for analysing the signals received by the receiving coil and reconstructing them into an image. The apparatus in the figure is set up to image a region which includes (for example) 20 the patient's heart.

The control means 4 is operated to employ a pulse sequence to take and process an image. Then, contrast agent contained in an injector 5 is operated to inject contrast agent into a vein in the groin of the patient through a tube 6 which communicates with a catheter injected into the vein. The control means 4 is arranged to produce a pulse sequence after a predetermined length of time, say, 20-30 seconds, after the contrast agent has been injected, this allowing the contrast agent to circulate around the patient's body. A second image (or series of images) is now produced which is enhanced by the contrast agent.]be two images could be combined, for example one could be subtracted from the other to highlight blood flow, or data from the series used to plot a curve of signal intensity.

This would enable a doctor to assess the extent, if any, to which perfusion had ceased in certain areas following a heart attack. Depending upon the results of the examination, a thrombolytic agent would then be manually injected into the patient.

The problem hitherto has been that the contrast agent would be excreted relatively slowly, and it would not be possible to check whether the treatment given as a result of the last perfusion assessment had been successful or not, since a pair of images would be required.

In accordance with the invention, a magnetic separator 8 is provided which circulates blood into the intravenous catheter via the tube 6 and out of an intra- arterial catheter via a tube 7. 7be intra-arterial catheter may be inserted for example into an artery in the groin of the patient. (The catheter may be connected to preferably adjacent arteries and veins in other peripheral regions of the patient e.g. the thigh or arm). The 6 separator 8 includes a pump for circulating the blood.

The magnetic separator takes advantage of the fact that the contrast agent is paramagnetic, much more so even than de-oxyhaemoglobin and the degradation products of haemoglobin, and much more strongly than oxyliaemoglobin is diamagnetic.

Me magnet in the magnetic separator 8 is a cryogenic magnet to generate a sufficiently high field, typically, 2-3 tesla.

An insert 9 is arranged in the path of the blood flow, aligned with the magnetic field.

The insert consists of a short tube 10, a pair of spools 11, 12 carrying a wire mesh web 13, and a drive mechanism (not shown). The web enters and leaves the short tube through slots 14,15. The spools are contained in a magazine 16.

Arterial blood enters the tube in the direction of the arrow A, and flows through the tube, through the wire mesh web, before being returned to the intravenous catheter through tube 6. The size of the openings in the mesh is at least twice the size of the largest cells in the blood, say, 20g pitch.

The mesh 13 is driven across the flow path from a tensioned starting roller I I to a driven pick-up roller 12. Before the pump in the magnetic separator is started, the magazine is loaded with blood or saline, to prevent any interstices of air being 7 introduced into the flow through the insert.

The pump and the drive mechanism are started simultaneously. The magnetic field B induces a magnetic field from one face of the mesh to the other, but counter to the main field. This results in large localised magnetic field gradients, particularly in the vicinity of the openings in the mesh.

These gradients are responsible for deflecting the differently magnetised particles of the blood flow to different extents. Weakly magnetised oxyhaemoglobin (the main component of the arterial flow) will be deflected less than (relatively) strongly magnetised contrast agent. This will assist the latter in adhering to the mesh by magnetic attraction. With suitable flow rates and magnetic fields B, the weakly magnetised oxyhaemoglobin will flow through the mesh and not adhere to it to any appreciable extent, as will any de-oxyhaemoglobin and degradation products of haemoglobin, while a certain amount of the contrast agent will.

The mesh is fed from one spool to the other, because adhered paramagnetic contrast agent would rapidly build up on the surface of a fixed mesh and reduce the large magnetic field gradients.

After use, the insert 9 is discarded, and a fresh one inserted, but it would in principle be possible to sterilise it for re-use.

8 In practice, the system will be set up with blood circulating via the two catheters through the separator 8, with the magnet of the separator switched off. Once a first set of observations has been made, before contrast agent has been injected and after contrast agent has been injected, the magnet of the separator is switched on and separation begins, When the contrast agent concentration in the blood has been sufficiently reduced (ideally to less than 5% of its initial concentration), the separation unit is switched off.

It is then possible to take another pair of images of the affected area of the heart, firstly with little concentration of contrast agent and secondly after a fresh injection of contrast agent.

Variations may be made without departing from the scope of the invention. The wire mesh could be replaced by wire or other magnetisable material not in the form of mesh, used to capture the more magnetised particles. The material helps with separation by resulting in large localised field gradients. 'llie separation depends on adhesion, and removal of the wire to provide a fresh surface for collecting more, for continuous separation.

Other magnetic separators may however be used.

The contrast agent need not be injected into the intravenous catheter connected to the pump. The injection of contrast agent could be made at another location. Instead of 9 using a magnet for providing the magnetic field B, the wire mesh itself could be magnetised. The catheter attached to the tubes 6,7 may extend in the body along the veins or arteries e.g. for angioplasty, they may extend to the region of the heart, but they need not do so, and simple short cannulas could be used as the catheters.

Claims

1. A separator for reducing the concentration of MRI contrast agent in the blood of a patient, which comprises a pump for connection to intraarterial and intravenous catheters, and a magnetic separator for separating contrast agent from the blood passing from the intra-arterial catheter to the intravenous catheter.

2. A separator as claimed in claim 1, in which the separator includes a wire mesh subject to the field of a magnet for promoting large magnetic field gradients in the vicinity of the mesh.

3. A separator as claimed in claim 2, in which the magnet is a cryogenic magnet.

4. A separator as claimed in claim 2 or claim 3, in which a drive mechanism is provided for feeding the mesh across a tube through which passes the blood to be separated.

5. A separator for reducing the concentration of MRI contrast agent in blood of a patient substantially as herein described with reference to the accompanying drawings.

6. Magnetic resonance imaging apparatus in combination with a separator as claimed in any one of claims I to 5.

1 11

7. A method of reducing the concentration of MRI contrast agent in the blood of a patient, which comprises circulating blood connected to an intra-arterial catheter and an intravenous catheter via a magnetic separator.