WO2006097727A1 - Diagnostic apparatus and method for measuring blood flow using electromagnetic sensors - Google Patents

Diagnostic apparatus and method for measuring blood flow using electromagnetic sensors Download PDF

Info

Publication number
WO2006097727A1
WO2006097727A1 PCT/GB2006/000931 GB2006000931W WO2006097727A1 WO 2006097727 A1 WO2006097727 A1 WO 2006097727A1 GB 2006000931 W GB2006000931 W GB 2006000931W WO 2006097727 A1 WO2006097727 A1 WO 2006097727A1
Authority
WO
WIPO (PCT)
Prior art keywords
diagnostic apparatus
magnetic field
skin
patient
regions
Prior art date
Application number
PCT/GB2006/000931
Other languages
French (fr)
Inventor
Jonathan Andrew Fuller
Nasr-Eddine Djennati
Original Assignee
Ivmd (Uk) Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ivmd (Uk) Limited filed Critical Ivmd (Uk) Limited
Publication of WO2006097727A1 publication Critical patent/WO2006097727A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0265—Measuring blood flow using electromagnetic means, e.g. electromagnetic flowmeter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/411—Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance

Definitions

  • the present invention relates to diagnostic apparatus for use in diagnosing conditions of the human or animal body.
  • the invention relates particularly, although not exclusively, to diagnostic apparatus capable of measuring blood flow within patient tissue.
  • the invention also relates to the use of such apparatus.
  • the ability to measure localised blood flow can be a useful diagnostic tool. For example being able to measure change in skin blood flow over time in response to various stimuli can be particularly useful. For example in testing for allergies a substance which is suspected of provoking an allergic reaction is applied to the skin. If application of the substance leads to an increased skin blood flow there is deemed to be an allergic reaction.
  • Methyl Nicotinate is applied to the skin of normal healthy patients it does not cause a blood flow reaction, but when it is applied to the skin of a patient suffering schizophrenia or extreme depression increased skin blood flow results.
  • Other conditions, such as bowel cancer, can be diagnosed with appropriate reagents.
  • Another example is the measurement of dilation of blood vessels close to the skin surface to measure the effectiveness of anti - inflammatory drugs.
  • diagnostic apparatus comprising means for measuring magnetic field strength at at least two regions at or near the surface of a patient's skin.
  • deoxygenated haemoglobin is strongly pa ⁇ Jnagnetic. Consequently when blood containing deoxygenated haemoglobin is immersed in a magnetic field, the field becomes slightly enhanced within the blood, and the distribution of magnetic flux density surrounding the blood is modified. This redistribution of flux can be detected by appropriately sensitive magnetic field detectors, and can be used to derive a measure of blood sample volume.
  • the apparatus comprises at least two magnetic field sensors, each field sensor may comprise one or more sensing elements and may in particular comprise an array of sensing elements.
  • Any suitable sensing element may be employed for example a galvomagnetic device such as a Hall Effect device, magneto resistive plate or coil.
  • the apparatus further preferably comprises a means for comparing the magnetic field measured by each sensor.
  • Said means may comprise an analogue and/or digital circuit.
  • the circuit enables the output from the two sensors to be adjusted to zero and then the differential output of the sensors to be measured.
  • the apparatus preferably further comprises means for applying a magnetic field to both regions where magnetic field strength is to be measured.
  • the field may be constant and homogeneous, or it may be inhomogeneous. Indeed an inhomogeneous field with a steep field gradient is desirable since this enhances the redistribution of flux density caused by changes in skin blood flow, leading to more accurate and effective measurement.
  • One or more permanent magnets may be used to provide the magnetic field.
  • One or more pole pieces may be used with the magnet or magnets to focus the field onto the regions where field is to be measured.
  • a pole piece or pieces are used to define a closed magnetic circuit in order to reduce the effect of extraneous magnetic fields.
  • a coil is used to provide a magnetic field.
  • the field may change with time and in particular may alternate.
  • the apparatus further preferably comprises a means for applying a reagent to the surface of a patient's skin.
  • Said means may comprise an absorbent pad arranged, in use, to be disposed between a magnetic sensor and a patient's skin.
  • the pad may be soaked with a desired reagent.
  • a gel pad could also be used.
  • Preferably a pad is provided for each magnetic field sensor and in use only one pad is soaked with reagent. This then ensures that conditions at the two or more regions of a patient's skin where magnetic field is measured are substantially the same, save for presence of the reagent.
  • the differential magnetic field measured by the sensors on introduction of the reagent is then indicative of any change in skin blood flow caused by the presence of the reagent.
  • the regions may be adjacent, or spaced apart.
  • the regions are preferably spaced apart by at least 2mm, but not by more than 15mm. It is preferred that the two or more magnetic field sensors lie in substantially the same plane.
  • a method of using apparatus according to the first aspect of the present invention comprising the steps of: measuring magnetic field strength at two regions of a patient's skin; applying a reagent to one of the regions of the patient's skin, but not the other; and noting any change in the relative magnetic field strength measured at the two regions.
  • Any change in magnetic field strength is indicative of a change in skin blood flow caused by application of the reagent.
  • a method of measuring a patient's skin blood flow comprising the step of measuring magnetic field strength at or near the surface of the patient's skin.
  • the apparatus comprises two matched Hall Effect devices 1, mounted in substantially the same plane. Associated with the Hall Effect devices is a rare earth magnet 2 and pole piece 3. The pole piece 3 is arranged to focus magnetic field produced by the magnet 2 onto the regions of the Hall Effect devices 3.
  • the Hall Effect devices 1 are each connected to a measurement circuit 4 arranged to determine the differential output of the Hall Effect devices 1 and display the output to a user via a display means 5.
  • circuit 4 first operates to reduce the outputs from the two Hall Effect devices 1 to zero.
  • Two absorbent pads 6 and 7 are provided. One pad 6 is soaked in a chosen reagent and both pads 6,7 are placed onto a patient's skin 8. The apparatus is then placed over the pads such that each pad 6,7 is disposed between a respective Hall
  • the circuit 4 then monitors the differential output of the Hall Effect devices in order to detect any relative change in magnetic field (and therefore implied change in skin blood flow) at the two regions of the patient's skin where the pads 6,7 are disposed.
  • the reagent has the effect of stimulating skin blood flow then as smaller blood vessels in the region of pad 6 dilate blood begins to flow closer to the skin 8 surface and therefore closer to the associated Hall Effect device 1.
  • the resultant change in the magnetic field at one Hall Effect device 1 but not the other will affect the differential output of the two devices and this is indicated to a user via the display 5. Because of differential measurement, any stray effects on the magnetic field or changes in blood characteristics have no effect on the output of the apparatus.
  • the apparatus can measure continuously and hence provide additional diagnostic information about reactions that occur over time.
  • the apparatus is capable of being self contained, portable and can be easily operated by unskilled users. As discussed above the apparatus has potential for use in a wide range of diagnostic treatment and other medical applications. These include: diagnosis of schizophrenia, manic depression and other psychotic disorders; diagnosis of allergic reactions; control and monitoring of drug therapy; control and monitoring of healing processes; control and monitoring of limb and tissue damage and healing, for example after surgery; and the diagnosis, control and monitoring of peripheral circulatory diseases.
  • diagnostic treatment and other medical applications include: diagnosis of schizophrenia, manic depression and other psychotic disorders; diagnosis of allergic reactions; control and monitoring of drug therapy; control and monitoring of healing processes; control and monitoring of limb and tissue damage and healing, for example after surgery; and the diagnosis, control and monitoring of peripheral circulatory diseases.

Abstract

Diagnostic apparatus including means (1) for measuring magnetic field strength at at least two regions at or near the surface of a patient's skin (8). Means (2,3) for applying a magnetic field at the two regions may be provided, as well as means (6,7) for applying a reagent to the patient's skin at one of those regions. Measurement of magnetic field enables skin blood flow to be determined in response to application of selected reagents enabling various diagnostic and other tests to be performed on a patient.

Description

DIAGNOSTIC APPARATUS AND METHOD FOR MEASURING BLOOD FLOW USING ELECTROMAGNETIC SENSORS
The present invention relates to diagnostic apparatus for use in diagnosing conditions of the human or animal body. The invention relates particularly, although not exclusively, to diagnostic apparatus capable of measuring blood flow within patient tissue. The invention also relates to the use of such apparatus.
The ability to measure localised blood flow can be a useful diagnostic tool. For example being able to measure change in skin blood flow over time in response to various stimuli can be particularly useful. For example in testing for allergies a substance which is suspected of provoking an allergic reaction is applied to the skin. If application of the substance leads to an increased skin blood flow there is deemed to be an allergic reaction.
Of more interesting diagnostic potential is the ability to test for a reaction to known markers for various illnesses. For example, it is known that when Methyl Nicotinate is applied to the skin of normal healthy patients it does not cause a blood flow reaction, but when it is applied to the skin of a patient suffering schizophrenia or extreme depression increased skin blood flow results. Other conditions, such as bowel cancer, can be diagnosed with appropriate reagents.
Another example is the measurement of dilation of blood vessels close to the skin surface to measure the effectiveness of anti - inflammatory drugs.
Conventionally, skin blood flow has been measured by infra red imaging and Doppler ultrasound techniques. However, because these techniques both require a direct view of the site to be measured their usefulness rn diagnostic techniques where a reagent is applied to a patient's skin is limited because they cannot be used to measure skin blood flow through a reagent soaked pad applied to the skin. Also conventional infra red imaging and Doppler ultrasound equipment is expensive and requires skilled operators.
It is one object of the present invention to provide an alternative diagnostic apparatus which may be used to measure skin blood flow of a patient. It is an object of embodiments of the invention to provide such apparatus capable of making a noninvasive measurement, of continuous operation, that does not require patient immobility, is safe, relatively simple to operate and inexpensive compared to conventional apparatus and can be operated by medical auxiliary staff.
According to a first aspect of the present invention there is provided diagnostic apparatus comprising means for measuring magnetic field strength at at least two regions at or near the surface of a patient's skin.
It is known that deoxygenated haemoglobin is strongly pa^Jnagnetic. Consequently when blood containing deoxygenated haemoglobin is immersed in a magnetic field, the field becomes slightly enhanced within the blood, and the distribution of magnetic flux density surrounding the blood is modified. This redistribution of flux can be detected by appropriately sensitive magnetic field detectors, and can be used to derive a measure of blood sample volume.
Thus for a patient in a magnetic field, such as the earth's magnetic field, changes in skin blood flow will result in changes in magnetic field strength near the surface of the patient's skin, and measurement of this magnetic field strength can be used to determine skin blood flow. By measuring magnetic field at two regions it is possible to compare the field strength, and hence skin blood flow, at the two regions. This can usefully give an accurate measure of the effect of a reagent when applied to one of the regions and not the other.
Preferably, the apparatus comprises at least two magnetic field sensors, each field sensor may comprise one or more sensing elements and may in particular comprise an array of sensing elements. Any suitable sensing element may be employed for example a galvomagnetic device such as a Hall Effect device, magneto resistive plate or coil.
The apparatus further preferably comprises a means for comparing the magnetic field measured by each sensor. Said means may comprise an analogue and/or digital circuit. Preferably the circuit enables the output from the two sensors to be adjusted to zero and then the differential output of the sensors to be measured.
The apparatus preferably further comprises means for applying a magnetic field to both regions where magnetic field strength is to be measured. The field may be constant and homogeneous, or it may be inhomogeneous. Indeed an inhomogeneous field with a steep field gradient is desirable since this enhances the redistribution of flux density caused by changes in skin blood flow, leading to more accurate and effective measurement.
One or more permanent magnets, especially rare earth magnets, may be used to provide the magnetic field. One or more pole pieces may be used with the magnet or magnets to focus the field onto the regions where field is to be measured. Preferably a pole piece or pieces are used to define a closed magnetic circuit in order to reduce the effect of extraneous magnetic fields.
In another arrangement a coil is used to provide a magnetic field. The field may change with time and in particular may alternate. The apparatus further preferably comprises a means for applying a reagent to the surface of a patient's skin. Said means may comprise an absorbent pad arranged, in use, to be disposed between a magnetic sensor and a patient's skin. The pad may be soaked with a desired reagent. A gel pad could also be used. Preferably a pad is provided for each magnetic field sensor and in use only one pad is soaked with reagent. This then ensures that conditions at the two or more regions of a patient's skin where magnetic field is measured are substantially the same, save for presence of the reagent. The differential magnetic field measured by the sensors on introduction of the reagent is then indicative of any change in skin blood flow caused by the presence of the reagent.
The regions may be adjacent, or spaced apart. The regions are preferably spaced apart by at least 2mm, but not by more than 15mm. It is preferred that the two or more magnetic field sensors lie in substantially the same plane.
According to another aspect of the present invention there is provided a method of using apparatus according to the first aspect of the present invention, with or without any of the preferred or optional features discussed above, comprising the steps of: measuring magnetic field strength at two regions of a patient's skin; applying a reagent to one of the regions of the patient's skin, but not the other; and noting any change in the relative magnetic field strength measured at the two regions.
Any change in magnetic field strength is indicative of a change in skin blood flow caused by application of the reagent.
According to another aspect of the invention there is provided a method of measuring a patient's skin blood flow comprising the step of measuring magnetic field strength at or near the surface of the patient's skin. In order that the invention may be more clearly understood, an embodiment thereof will now be described by way of example, with reference to the accompanying drawing, the single figure of which is a schematic diagram of apparatus according to the invention in use.
Referring to the drawing the apparatus comprises two matched Hall Effect devices 1, mounted in substantially the same plane. Associated with the Hall Effect devices is a rare earth magnet 2 and pole piece 3. The pole piece 3 is arranged to focus magnetic field produced by the magnet 2 onto the regions of the Hall Effect devices 3.
The Hall Effect devices 1 are each connected to a measurement circuit 4 arranged to determine the differential output of the Hall Effect devices 1 and display the output to a user via a display means 5.
In use the circuit 4 first operates to reduce the outputs from the two Hall Effect devices 1 to zero.
Two absorbent pads 6 and 7 are provided. One pad 6 is soaked in a chosen reagent and both pads 6,7 are placed onto a patient's skin 8. The apparatus is then placed over the pads such that each pad 6,7 is disposed between a respective Hall
Effect device 1 and a patient's skin 8. The circuit 4 then monitors the differential output of the Hall Effect devices in order to detect any relative change in magnetic field (and therefore implied change in skin blood flow) at the two regions of the patient's skin where the pads 6,7 are disposed.
If the reagent has the effect of stimulating skin blood flow then as smaller blood vessels in the region of pad 6 dilate blood begins to flow closer to the skin 8 surface and therefore closer to the associated Hall Effect device 1. The resultant change in the magnetic field at one Hall Effect device 1 but not the other will affect the differential output of the two devices and this is indicated to a user via the display 5. Because of differential measurement, any stray effects on the magnetic field or changes in blood characteristics have no effect on the output of the apparatus. The apparatus can measure continuously and hence provide additional diagnostic information about reactions that occur over time.
The apparatus is capable of being self contained, portable and can be easily operated by unskilled users. As discussed above the apparatus has potential for use in a wide range of diagnostic treatment and other medical applications. These include: diagnosis of schizophrenia, manic depression and other psychotic disorders; diagnosis of allergic reactions; control and monitoring of drug therapy; control and monitoring of healing processes; control and monitoring of limb and tissue damage and healing, for example after surgery; and the diagnosis, control and monitoring of peripheral circulatory diseases. The above embodiment is described by way of example. Many modifications are possible without departing from the invention.

Claims

1. Diagnostic apparatus comprising means for measuring magnetic field strength at at least two regions at or near the surface of a patient's skin.
2. Diagnostic apparatus as claimed in claim 1 comprising at least two magnetic field sensors, each sensor comprising one or more sensing elements.
3. Diagnostic apparatus as claimed in claim 2, wherein each sensor comprises an array of sensing elements.
4. Diagnostic apparatus as claimed in any preceding claim comprising means for comparing the magnetic field measured at each region.
5. Diagnostic apparatus as claimed in claim 4, when dependent on either claim 2 or 3 wherein the means for comparing the magnetic field measured at each region comprises a circuit which enables the output from the two sensors to be adjusted to zero and then the differential output of the sensors to be measured.
\ J
6. Diagnostic apparatus as claimed in any preceding claim comprising means for applying a magnetic field to both regions where magnetic field strength is to be measured.
7. Diagnostic apparatus as claimed in claim 6, wherein the means for applying a magnetic field applies an inhomogeneous field with a steep gradient.
8. Diagnostic apparatus as claimed in either claim 6 or 7, wherein the means for applying a magnetic field comprises one or more permanent magnets.
9. Diagnostic apparatus as claimed in claim 8, wherein the one or more permanent magnets are associated with one or more pole pieces operative to focus the magnetic field onto the regions where the magnetic field is to be measured.
10. Diagnostic apparatus as claimed in claim 9, wherein one or more pole pieces define a closed magnetic circuit.
11. Diagnostic apparatus as claimed in either claim 6 or 7, wherein the means for applying a magnetic field comprises one or more coils.
12. Diagnostic apparatus as claimed in any preceding claim comprising means for applying a reagent to the surface of the patient's skin.
13. Diagnostic apparatus as claimed in claim 12, when dependent, directly or indirectly, on claim 2 wherein said means for applying a reagent comprises a pad so that in use it is disposed between a magnetic sensor and a patient's skin.
14. Diagnostic apparatus as claimed in claim 13, wherein the pad is an absorbent pad.
15. Diagnostic apparatus as claimed in claim 13, wherein the pad is a gel pad.
16. Diagnostic apparatus as claimed in any of claims 13 to 15, wherein a pad is associated with each magnetic field sensor.
17. Diagnostic apparatus as claimed in any preceding claim, wherein the two regions are spaced apart by at least 2mm.
18. Diagnostic apparatus as claimed in claim 2 and any of claims 3 to 17 when dependent on claim 2, wherein the magnetic sensors lie in substantially the same plane.
19. A method of use of the diagnostic apparatus as claimed in any preceding claim, the method comprising the steps of: measuring magnetic field strength at two regions of a patient's skin; applying a reagent to one of the regions of the patient's skin, but not the other; and noting any change in the relative magnetic field strength measured at the two regions.
20. A method of measuring a patient's skin blood flow comprising the step of measuring magnetic field strength at or near the surface of the patient's skin.
PCT/GB2006/000931 2005-03-15 2006-03-15 Diagnostic apparatus and method for measuring blood flow using electromagnetic sensors WO2006097727A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0505244A GB0505244D0 (en) 2005-03-15 2005-03-15 Diagnostic apparatus
GB0505244.4 2005-03-15

Publications (1)

Publication Number Publication Date
WO2006097727A1 true WO2006097727A1 (en) 2006-09-21

Family

ID=34509059

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2006/000931 WO2006097727A1 (en) 2005-03-15 2006-03-15 Diagnostic apparatus and method for measuring blood flow using electromagnetic sensors

Country Status (2)

Country Link
GB (1) GB0505244D0 (en)
WO (1) WO2006097727A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4707663A (en) * 1985-08-15 1987-11-17 Fonar Corporation Nuclear magnetic resonance apparatus using low energy magnetic elements
US5794622A (en) * 1992-06-04 1998-08-18 Biomagnetic Technologies, Inc. Measurement of fluid flows in a living organism
US20020138049A1 (en) * 1998-06-10 2002-09-26 Allen Mark G. Microneedle devices and methods of manufacture and use thereof
US20030016010A1 (en) * 2001-07-19 2003-01-23 Hitachi, Ltd. Apparatus for measuring a magnetic field
US20050054939A1 (en) * 2002-01-15 2005-03-10 Orsan Medical Equipment Ltd. Device for monitoring blood flow to brain

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4707663A (en) * 1985-08-15 1987-11-17 Fonar Corporation Nuclear magnetic resonance apparatus using low energy magnetic elements
US5794622A (en) * 1992-06-04 1998-08-18 Biomagnetic Technologies, Inc. Measurement of fluid flows in a living organism
US20020138049A1 (en) * 1998-06-10 2002-09-26 Allen Mark G. Microneedle devices and methods of manufacture and use thereof
US20030016010A1 (en) * 2001-07-19 2003-01-23 Hitachi, Ltd. Apparatus for measuring a magnetic field
US20050054939A1 (en) * 2002-01-15 2005-03-10 Orsan Medical Equipment Ltd. Device for monitoring blood flow to brain

Also Published As

Publication number Publication date
GB0505244D0 (en) 2005-04-20

Similar Documents

Publication Publication Date Title
KR100618382B1 (en) Method for measuring blood nmr relaxation time and apparatus using the same
US20090018432A1 (en) Methods and apparatus for imaging with magnetic induction
Jehenson et al. Change in human cardiac rhythm induced by a 2-T static magnetic field.
WO2003075745A3 (en) Detection, diagnosis, and monitoring of a medical condition or disease with artificial olfactometry
JPH08206096A (en) Method of detecting presence of ferromagnetic material body in animal
EP1552783B1 (en) Device for and method of measuring blood flow using bio-photon emission
JPH10505776A (en) Use of magnetic implants to locate patients
Ng et al. Human neoplasm pH and response to radiation therapy: P-31 MR spectroscopy studies in situ.
EP2406650A1 (en) Arrangement and method for measuring a magnetic material in a region of action
Romanelli et al. Use of a durometer to measure the degree of skin induration in lipodermatosclerosis
US20040267165A1 (en) Tactile breast imager and method for use
Li et al. Design of a noninvasive bladder urinary volume monitoring system based on bio-impedance
CN106361285A (en) Detecting and treating method for sub-health status of human body of intelligent foot biological health information management and health-care decision making system
Ploutz-Snyder et al. Evaluation of spastic muscle in stroke survivors using magnetic resonance imaging and resistance to passive motion
JP2004527300A (en) Method and apparatus for detecting functional and metabolic data of a living body
Steinberg et al. A new method for tumor detection using induced acoustic waves from tagged magnetic nanoparticles
Turpin et al. Electrodermal activity
WO2006097727A1 (en) Diagnostic apparatus and method for measuring blood flow using electromagnetic sensors
James et al. Undisclosed and undetected foreign bodies during MRI screening resulting in a potentially serious outcome
JP2001276018A (en) Method and device for optimally utilizing output ability of magnetic resonance tomographic equipment
Arunachalam et al. Design and analysis of finite element based sensors for diagnosis of liver disorders using biocompatible metals
Bruno et al. Hybrid system for magnetic and acoustic measurement
Boy et al. Diffusion-weighted MR imaging and Doppler ultrasonography in the evaluation of renal parenchyma in acute ureteral obstruction
RU2543293C2 (en) Individual's physiological parameters control device
Sarkawi et al. Non–invasive Fetal Scalp pH Measurement Utilizing Magnetic Induction Spectroscopy Technique

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

WWW Wipo information: withdrawn in national office

Country of ref document: RU

122 Ep: pct application non-entry in european phase

Ref document number: 06726398

Country of ref document: EP

Kind code of ref document: A1

WWW Wipo information: withdrawn in national office

Ref document number: 6726398

Country of ref document: EP