Title of Invention

''A DEVICE FOR ELECTRON PARAMAGNETIC RESONANCE IMAGING USING MICROWAVE BRIDGE TRANSLATION MODULE

Abstract

A device for Electron Paramagnetic Resonance Imaging using microwave bridge translation module comprising a microwave bridge consisting of a source of electromagnetic radiation (22) in the microwave region, and attenuation and phase shift elements, the output of the said source (22) is connected to one arm of a circulator or magic tee (23), one arm of which is coupled to a resonator (24) through an iris coupling, another arm being connected to a conventional microwave detector (26), the output of which is connected to one input of a phase sensitive detector (PSD) (27), whose second input is connected to one output of a conventional modulator (25), a second output of the said modulator (25), is fed to the modulation coils (32), associated with the resonator (24), the output of the PSD (27) being fed to an analog-to-digital converter (ADC) (8), whose output is connected to a Computer (29), the resonator (24) being placed in a magnetic field between the north pole and the south pole of a magnet (30), characterized in that the microwave bridge translation module (31) adaptable for displacement of the bridge consisting of a source of electromagnetic radiation (22), circulator (23), resonator (24) with the sample and microwave detector (26) in such a way that the resonator (24) is located optimally off-center in the magnetic field, the imaging being performed either in continuous wave or in pulsed mode.

Full Text

The present invention relates to a device for Electron Paramagnetic Resonance Imaging using microwave bridge translation module. The device of the present invention has potential use in one-,two-or three-dimensional Electron Paramagnetic Resonance (EPR) Imaging. It has potential application in leather industry for detecting the presence and distribution of chromium in leather. The device may also be used in the drugs, Pharmaceuticals and cosmetic industry. It is also envisaged to have use for detecting the presence and Distribution of radicals including the nitoxide radical in metabolites for medical purpose. Further.it has potential application in mineralogical applications and also in foodstuffs industry. Electron Paramagnetic Resonance (EPR), which is also known as Electron Spin Resonance (ESR), is a technique of radio frequency (rf) / microwave spectroscopy that detects free radicals, certain transition metal complexes, certain rare earth metal complexes, triplet state molecules and the like, by virtue of the presence of unpaired electrons in such species ('spins'). The measurement is performed by locating the sample of interest (usually liquid or solid) in a suitable resonator (eg. cavity, slow wave structure, etc.) placed in a spatially homogeneous magnetic field and irradiating it with electromagnetic (em) radiation whose frequency matches the characteristic precession frequency of the electron spins in the external field, the resonance frequency being given by the equation where g is the spectroscopic splitting factor (Lande fector, or simply the g-factor), ß is the Bohr magneton, B0 is the intensity of the magnetic field and h is Planck's constant divided by 2π. This 'first order' equation for the resonance frequency is usually modified by the addition of other contributory terms involving internal (or local) fields from other unpaired electrons and / or nuclear spins. The resonant absorption (or emission) of em radiation under these conditions is customarily recorded by varying the intensity of the external magnetic field across the resonance condition, holding the frequency of the em radiation constant in continuous wave (cw) mode. In order to minimize dc (direct current) drifts during the course of the field scan and to improve signal-to-noise ratio, it is customary to employ field modulation, typically at 100 Hz to 100 kHz, employing a set of modulation coils mounted in the resonator / cavity and perform phase sensitive detection (PSD) of the output of the em detector (eg. Diode detector). Normally, EPR measurements are employed to access detailed information about the electronic structure, shape and dynamics of molecular species, the sample and magnetic field being made as homogeneous as possible. The magnetic field is usually generated by a permanent magnet, superconducting electromagnet, or, more frequently, by a resistive electromagnet. The intensity of the field generated by the magnet is usually not higher than 1.5 Tesla (T), although very low fields, of the order of 0.01 T, or very high fields, of the order of 3.4 T may also be employed. Correspondingly, the sample placed in the resonator is irradiated typically with microwaves from a microwave bridge, or with radio frequency radiation. In the pulsed mode of operation, the continuous wave (cw) microwave bridge is replaced with a pulsed microwave bridge, the microwaves are amplified with a Traveling Wave Tube (TWT) Amplifier to produce typically upto 1 kWatt of power in pulsed output mode, such microwave pulses then being fed to the resonator. Often a resonator with lower quality factor, Q, is used for pulsed applications, in the interest of reducing the ring-down time ('dead time') of the system, to enable near 'zero time' detection of the resulting ESR signals. The same basic experiment may be used in quite a different mode, however, to detect macroscopic molecular distributions in an inhomogeneous object. Such a distribution function provides an 'image' of the object in question. The primary emphasis of such a measurement is not molecular structure, but macroscopic molecular distribution. This type of information is accessed by locating the object of interest in a suitable resonator in a magnetic field that has spatial variation, ie, gradients. Under these conditions, the resonance frequency is given by the equation where, G indicates gradient vector, while r indicates the position vector in the sample. The resolution of an EPR image is dependent on a number of parameters, including the intensity of the magnetic field gradient, the intrinsic width of the basic EPR resonance of the species in question (the 'linewidth'), the signal-noise-ratio per volume element of the sample, molecular diffusion processes, etc. In general, the EPR linewidth is of the order of several Gauss (1 Gauss = 10-4 Tesla), or several Megahertz in frequency units. The resolution R expected on the basis of the first two parameters may be given as: where Avi/2 denotes the linewidth and G, the gradient amplitude. It is customary to generate the gradient by additional sets of anti-Helmholtz or Anderson coils located in the main magnetic field. When currents are passed through such water- or forced air-cooled coils, sizeable gradients may be generated, with amplitudes upto about 1 T m-1 (100 G cm"1). One set of coils is typically employed for each of the three orthogonal directions in space. Because the inverse of the EPR linewidth is typically short compared to gradient switching times, it is customary to acquire the signal in the presence of the gradient, then reorient the sample with respect to the gradient (eg. by rotating the gradient through adjustment of the current amplitudes in two sets of gradient coils to obtain a two-dimensional image). Reconstruction of the resulting series of 'projections' then yields the desired image. As reported by Maresch et al (Physica B, 138, 261, 1986), it is possible, under special circumstances, to pulse the gradient and acquire ESR images as in Nuclear magnetic Resonance (NMR) Fourier imaging. This entails the construction of a special, usually small, gradient coil assembly with low inductance, permitting short gradient pulse rise and fall times, the experiment being then performed with an ESR sample that gives rise to a single sharp resonance (the linewidth being of the order of 20-50 kHz, instead of being in the typical range of 1-10 MHz) in the absence of gradients. The main objective of the present invention is to provide a device for Electron Paramagnetic Resonance Imaging using a microware bridge obviates the special requirements, limitations and drawbacks stated above. Another objective of the present invention is to provide a device for EPR imaging using naturally occurring field gradient. Yet another objective of the present invention is to provide a device to use a field gradient of amplitude of minimum 5 T/m. Still another objective of the present invention is to provide a device devoid of gradient coil, gradient amplifier and the associated cooling system for generating EPR images. Yet another objective of the present invention is to provide a device to image EPR samples like nitroxide radicals, having larger line width in the range of 1-10 MHz. Still another objective of the present invention is to provide a device to acquire ESR images in cw mode, as well as in pulsed mode of operation. In the drawings accompanying this specification, Figure 1 represents a schematic block diagram of a typical EPR (ESR) spectrometer, conventionally used for measuring EPR. Figure 2 represents a schematic block diagram of typical EPR (ESR) spectrometer, including one set of gradient coils driven by a gradient amplifier, used for EPR imaging. Figure 3 represents a schematic block diagram for EPR imaging with Microwave (MW) bridge translation system. Different components of Figure 1 are as follows: 1 refers to a source of electromagnetic radiation in the microwave or rf region 2 refers to Circulator or Magic Tee 3 refers to resonator incorporating an iris coupling 4 refers to a modulator 5 refers to microwave detector, eg. diode detector 6 refers to phase sensitive detector (PSD) 7 refers to analog-to-digital converter (ADC) 8 refers to Computer 9 refers to Magnet with North and South pole. 10 refers to modulation coils Different components of Figure 2 are as follows: 11 refers to a source of electromagnetic radiation in the microwave or rf region 12 refers to Circulator or Magic Tee 13 refers to resonator incorporating an iris coupling 14 refers to a modulator 15 refers to microwave detector, eg. diode detector 16 refers to phase sensitive detector (PSD) 17 refers to analog-to-digital converter (ADC) 18 refers to Computer 19 refers to Magnet with North and South pole 20 refers to gradient amplifier and coils 21 refers to modulation coils Different components of Figure 3 are as follows. 22 refers to a source of electromagnetic radiation in the microwave or rf region 23 refers to Circulator or Magic Tee 24 refers to resonator incorporating an iris coupling 25 refers to a modulator 26 refers to microwave detector, eg. diode detector 27 refers to phase sensitive detector (PSD) 28 refers to analog-to-digital converter (ADC) 29 refers to Computer 30 refers to Magnet with North and South pole 31 refers to microwave bridge translation module 32 refers to modulation coils Accordingly the present invention provides a device for electron paramagnetic resonance imaging using microwave bridge translation module comprising a microwave bridge consisting of a source of electromagnetic radiation (22) in the microwave region, and attenuation and phase shift elements, the output of the said source (22) is connected to one arm of a circulator or magic tee (23), one arm of which is coupled to a resonator (24) through an iris coupling, another arm being connected to a conventional microwave detector (26), the output of which is connected to one input of a phase sensitive detector (PSD) (27), whose second input is connected to one output of a conventional modulator (25), a second output of the said modulator (25) is fed to the modulation coils (32) associated with the resonator (24), the output of the PSD (27) being fed to an analog-to-digital converter (ADC) (28), whose output is connected to a Computer (29), the resonator (24) being placed in a magnetic field between the north pole and the south pole of a magnet (30), characterized in that the microwave bridge translation module (31) adaptable for displacement of the bridge consisting of a source of electromagnetic radiation (22), circulator (23), resonator (24) with the sample and microwave detector (26) in such a way that the resonator (24) is located optimally off-center in the magnetic field, the imaging being performed either in continuous wave or in pulsed mode. In an embodiment of the present invention, the source of electromagnetic radiation used may be such as klystron, Gunn diode oscillator, and Impact Avalanche and Transit Time (IMPATT) diode. In another embodiment of the present invention, the resonator used may be such as slow wave helical structure, dielectric resonator, cylindrical resonator, rectangular resonator, slotted resonator. In yet another embodiment of the present invention, the means of orienting the sample may be such as manually settable or computer controlled goniometer. In still anolher embodimentof Ihe presenl invenlion, Ihe reorienlalion of the sample may be such as to vary polar angle or azimuthal angle of the sample with respect to the field. In yet another embodiment of the present invenlion, the minimum number of EPR profiles to be laken for generating the image may be 12. The presenl invenlion is described below in delail. The sample under invesligalion is placed inside a conventional resonator (24) and oriented with the help of a goniometer. The resonator (24) is located not in the middle oft he main magnel (30), bul instead, in such a region wherethe spalial varialion of the field is more man 5 T/m. The oplion of conlrolled and reproducibletranslalion of the microwave bridge / resonalor assembly in two or three orthogonal directions helps in locating the same at the desired favorable posilion in the magnelic field. The resonalor (24) is then tuned and malched wilh the frequency source and the field modulalion is set at an amplilude less than the linewidlh of the sample under invesligalion. The EPR speclral profile of the sample is then recorded by convenlional field sweep melhod. The profile is optimized by varying the modulalion frequency. The same process is repeated to get a minimum of 12 profiles, each with a different orientation of the sample. These profiles are then processed by the conventional method of projection reconstruction including shift, deconvolution and back projection to generate the desired two or three dimensional images. The novelty and non-obviousness of the present invention lies in the incorporation of microwave bridge translation module (31), whereby the resonator containing the sample can be placed, unlike in the conventional device where the sample placed in the resonator has necessarily to be put in the centre of the magnetic field necessitating additional hardware and control system to generate the gradient, instead at a convenient optimal location in the field ensuring the optimal use of field intensity and the naturally occurring gradient without using the conventional hardware and control system for the imaging application. The following examples are given by way of illustration only and therefore should not be construed to limit the scope of the present invention. Example 1 8 mg of Cr (V) hmba (hmba: 2-hydroxy-2-methylbutyric acid) powder was taken in two capillary tubes of diameter 2 mm after imposing a pair of empty tubes of diameter 3 mm between the said 2 mm tubes containing sample were placed in the standard rectangular TE102 cavity resonator of a Bruker EMX 10/2.7 EPR spectrometer parallel to the magnetic field direction z and the field modulation was set to a frequency of 100 kHz and an amplitude of 0.5 G. The resonator was displaced 10 cm from the origin (center of the magnet) in the horizontal x direction, while being centered in the z and vertical y directions. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 15° from the z axis. The process was then repeated 12 times in a similar way, subjecting the sample to a reorientation of 15° each time, thereby getting a total of 12 profiles. The profiles were processed using IDL software to get the 2-dimensional image of the sample. The image was in conformity with morphology of the phantom object. Example 2 0.25 ml of a solution of 4-hydroxy-TEMPO (TEMPO: 2,2,6,6-tetramethyl piperidine-1-oxyl radical) was taken in two short capillary tubes of diameter 2 mm after interposing a pair of empty tubes of diameter 3 mm between the said 2 mm tubes containing sample were placed in the standard dielectric resonator of a Bruker EMX 10/2.7 EPR spectrometer parallel to the magnetic field direction z and the field modulation was set to a frequency of 100 kHz and an amplitude of 0.5 G. The resonator was displaced 10 cm from the origin (center of the magnet) in the horizontal x direction, while being centered in the z and vertical y directions. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 10° from the z axis. The process was then repeated for 18 times in a similar way, subjecting the sample to a reorientation of 10° each time, thereby getting a total of 18 profiles. The profiles were processed using IDL software to get the 3-dimensional image of the sample after orthogonal mounting of the phantom followed by a similar rotation procedure as before. The image was in conformity with morphology of the phantom object. Example 3 0.25 ml of a solution of TEMPO was taken in two capillary tubes of diameter 2 mm after interposing a pair of empty tubes of diameter 3 mm between the said 2 mm tubes containing sample were placed in the standard cylindrical resonator of a Bruker EMX 10/2.7 EPR spectrometer parallel to the magnetic field direction z and the field modulation was set to a frequency of 100 kHz and an amplitude of 0.5 G. The resonator was displaced 10 cm from the origin (center of the magnet) in the horizontal x direction, while being centered in the z and vertical y directions. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 10° from the z axis. The process was then repeated 18 times in a similar way, subjecting the sample to a reorientation of 10° each time, thereby getting a total of 18 profiles. The profiles were processed using IDL software to get the 2-dimensional image of the sample. The image was in conformity with morphology of the phantom object. The main advantages of the present invention are the following. 1. The device of the present invention provides for controlled and reproducible translation of the microwave bridge / resonator assembly in two or three orthogonal directions, in order to locate the resonator at the desired favorable position in the magnetic field. 2. The naturally occurring field gradient alone is used for EPR imaging by the present device. 3. The present device is devoid of gradient coil, gradient amplifier and the associated cooling system for generating EPR images. 4. Field modulation amplitude is maintained below that of the linewidth of the magnetic field. 5. Imaging of EPR samples like nitroxide radicals, having larger linewidth in the range of 1-10 MHz, is possible by using the device of the present invention. 6. The device permits acquisition of ESR images in cw mode, as well as in pulsed mode of operation. We Claim: 1. A device for electron paramagnetic resonance imaging using microwave bridge translation module comprising a microwave bridge consisting of a source of electromagnetic radiation (22) in the microwave region, and attenuation and phase shift elements, the output of the said source (22) is connected to one arm of a circulator or magic tee (23), one arm of which is coupled to a resonator (24) through an iris coupling, another arm being connected to a conventional microwave detector (26), the output of which is connected to one input of a phase sensitive detector (PSD) (27), whose second input is connected to one output of a conventional modulator (25), a second output of the said modulator (25) is fed to the modulation coils (32) associated with the resonator (24), the output of the PSD (27) being fed to an analog-to-digital converter (ADC) (28), whose output is connected to a Computer (29), the resonator (24) being placed in a magnetic field between the north pole and the south pole of a magnet (30), characterized in that the microwave bridge translation module (31) adaptable for displacement of the bridge consisting of a source of electromagnetic radiation (22), circulator (23), resonator (24) with the sample and microwave detector (26) in such a way that the resonator (24) is located optimally off-center in the magnetic field, the imaging being performed either in continuous wave or in pulsed mode. 2. A device, as claimed in claim 1, wherein the source of electromagnetic radiation used is klystron, Gunn diode oscillator, and Impact Avalanche and Transit Time (IMPATT) diode. 3. A device as claimed in claim-1, wherein the resonator used is slow wave helical structure, dielectric resonator, cylindrical resonator, rectangular resonator, slotted resonator. 4. A device for Electron Paramagnetic Resonance Imaging using microwave bridge translation module, substantially as herein described with reference to the examples and the drawings accompanying the specification.

Documents:

789-del-2000-abstract.pdf

789-del-2000-claims.pdf

789-del-2000-correspondence-others.pdf

789-del-2000-correspondence-po.pdf

789-del-2000-description (complete).pdf

789-del-2000-drawings.pdf

789-del-2000-form-1.pdf

789-del-2000-form-19.pdf

789-del-2000-form-2.pdf

789-del-2000-form-3.pdf

789-del-2000-petition-137.pdf

789-del-2000-petition-138.pdf