Title of Invention

"AN IMPROVED DEVICE FOR ELECTRON PARAMAGNETIC RESONANCE IMAGING USING A HIGH AMPLITUDE MODULATOR"

Abstract An improved device for electron paramagnetic resonance imaging, using high amplitude modulator which comprises a microwave bridge consisting of a source of electromagnetic radiation (12) in the microwave region, and attenuation and phase shift elements, the output of the said source (12) is connected to one arm of a circulator or magic tee (13), another arm of the said magic tee (13) is coupled to a resonator (14) through an iris coupling, a third arm being connected to a microwave detector, e.g. diode detector (16), the output of the said microwave detector is connected to one input of a phase sensitive detector (PSD) (17),characterized in that second input of the said phase sensitive detector is connected to one output of a high amplitude modulator (15),for producing large field modulation amplitudes of at least 20 Gauss, second output of the said modulator (15) is connected to the modulation coils to get rotated externally and associated with the said resonator (14), the output of the said PSD (17) being connected to an analog-to-digital converter (ADC) (18) , output of the said ADC is connected to a computer (19), the said resonator (14) being placed in the center of a magnetic field between the North pole and South pole of a magnet (20).
Full Text The present invention relates to an improved device for Electron Paramagnetic Resonance Imaging using a high More particularly, the present invention relates to an improved device for one-, two- or three- dimensional Electron Paramagnetic
Resonance (EPR) Imaging by employing a technique of radiofrequency or
microwave spectroscopy that detects and measures the spatial distribution of 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. It has potential application in leather industry for detecting the presence and distribution of chromium in leather. It may also be used in the drugs, Pharmaceuticals and cosmetics industry. The device is also envisaged to have use for detecting the presence and distribution of radicals including the nitroxide radical in metabolites for medical purpose. Further, it has potential use in mineralogical applications and also in foodstuffs industry.
Electron Paramagnetic Resonance, which is also known as Electron Spin Resonance (ESR), is one of the spectroscopic tools to study the molecular structure of organic free radicals and inorganic complexes. 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 is given by the following equation
where g is the spectroscopic splitting factor (Lande factor, or simply the g-factor), ß is the Bohr magneton, BO 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 additional factors 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 direct current (dc) 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 spatially homogeneous as possible.
This prompted researchers to study molecular distributions as well as molecular structure in inhomogeneous systems by employing the imaging technique, where the 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 following 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 = 10-4Tesla), or several Megahertz in frequency units. The resolution R expected on the basis of the first two parameters may be given as:
Here, denotes the linewidth, while G denotes the gradient amplitude.
As reported by Swartz et al (Journal of Magnetic Resonance, 84, 247,
1989), Eaton et al ("EPR Imaging and in vivo EPR," CRC Press, Boston, 1991),
I Eaton et al (Concepts in Magnetic Resonance, 1, 49, 1994), Eaton et al (Chemical
Physics Letters, 142, 567, 1987) and Symons et al (Journal of Magnetic Resonance, 92, 480, 1991), EPR imaging has conventionally been carried out by continuous wave (CW) method using a standard EPR spectrometer, where the frequency of radiation is held constant, while the magnetic field is swept. Depending on the nature of experiment, gradient currents are turned on to do 1 -Dimensional, 2-Dimensional or 3-Dimensional EPR imaging or spectral- spatial work.
It is customary to generate the gradient(s) 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 Tesla m-1 (100 Gauss 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 hi two sets of gradient coils to obtain a two-dimensional image). Projection reconstruction of the resulting series of profiles, including suitable shift, deconvolution and back projection operations then yields the desired image.
The main objective of the present invention is to provide an improved device for. ^^ Electron Paramagnetic Resonance Imaging using a high ammplitude modivater which
obviates the special requirements and limitations stated above.
Another objective of the present invention is to generate the desired EPR images, without employing additional sets of gradient coils.
Yet another objective of the present invention is to operate the field modulation at a high amplitude typically more than 20 Gauss, in the range of 14-78 Gauss in the present system.
Still another objective of the present invention is to exploit the intrinsic
inhomogeneity or gradient in the modulation field to generate the desired
information.
Yet another objective of the present invention is to provide an option to rotate the
sample in the resonator.
In the drawings accompanying this specification,
Figure 1 represents a schematic block diagram of typical EPR (ESR) spectrometer,
including one set of gradient coils driven by a gradient amplifier, used for
conventional EPR imaging.
Figure 2. represents a schematic block diagram of an improved device for EPR
imaging.
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 gradient amplifier
11. refers to modulation coils
Different components of Figure 2 are as follows:
12. refers to a source of electromagnetic radiation in the microwave or rf region
13. refers to Circulator or Magic Tee
14. refers to resonator incorporating an iris coupling
15. refers to a high amplitude modulator, capable of producing modulation amplitude in
the range of 14-78 Gauss cm -116. refers to microwave detector, eg. Diode detector
17. refers to phase sensitive detector (PSD)
18. refers to analog-to-digital converter (ADC)
19. refers to Computer
20. refers to Magnet with North and South pole
21. refers to Modulation coils
Accordingly the present invention provides an improved device for electron paramagnetic resonance imaging, characterized by a microwave bridge consisting of a source of electromagnetic radiation (12) in the microwave region, and attenuation and phase shift elements, the output of the said source (12) is connected to one arm of a circulator or magic tee (13), another arm of the said magic tee (13) is coupled to a resonator (14) through an iris coupling, a third arm being connected to a microwave detector, e.g. diode detector (16), the output of the said microwave detector is connected to one input of a phase sensitive detector (PSD) (17), second input of the said phase sensitive detector is connected to one output of a high amplitude modulator (15),for producing large field modulation amplitudes of at least 20 Gauss, second output of the said modulator (15) is connected to the modulation coils to get rotated externally and associated with the said resonator (14), the output of the said PSD (17) being connected to an analog-to-digital converter (ADC) (18), output of the said ADC is connected to a computer (19), the said resonator (14) being placed in the center of a magnetic field between the North pole and South pole of a magnet (20).

In an embodiment of the present invention, the source of electromagnetic radiation
used may be such as klystron, Gunn diode oscillator, 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 another embodiment of the present invention, the reorientation of the sample
may be such as to vary polar angle or azimuthan angle of the sample with respect to the
field.
In yet another embodiment of the present invention, the minimum number of EPR
profiles to be taken for generating the image may be 12.
The working of the device of the present invention is described below in detail.
The sample under investigation is placed inside a conventional resonator (14) and oriented externally with the help of a goniometer (not shown in the drawing). The resonator (14) is then tuned and matched with the frequency source (1) and the field modulation is set at an amplitude typically of at least 20 Gauss. EPR spectral profile of the sample is then recorded by conventional field sweep method. The profile may be optimized by varying the modulation 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 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 using a high amplitude modulator (15) enabling large field modulation amplitudes, typically at least 20 Gauss, to exploit the inherent gradient of the field modulation, thereby avoiding use of additional sets of gradient coils to generate two or three dimensional EPR images, whereby the additional expenditure for providing gradient coils, gradient amplifiers and the associated cooling system, as is essential in case of conventional EPR imaging systems, can be avoided.
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 interposing 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 32.18 Gauss, the maximum legal setting on this system. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 15° from the z axis and the process was repeated. In a similar way, the process was repeated 12 times by 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 the 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 2mm 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 20 G. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 10° from the z axis and the process was repeated. In a similar way, the process was repeated 18 times by 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 the 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 20 G. The profile of the sample was obtained. The sample was then reoriented using a manual goniometer to 10° from the z axis and the process was repeated. In a similar way, the process was repeated 18 times by 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 the morphology of the phantom object.
The main advantages of the present invention are the following.
1. It is a much simpler process for EPR imaging of paramagnetic substances.
2. The device of the present invention generates one, two- or three- dimensional
EPR images, without employing additional sets of gradient coils.
3. No arrangement is required for cooling, unlike the conventional system of EPR
imaging with gradient coils.
4. It generates one, two- or three- dimensional EPR images, without employing
additional sets of gradient amplifiers.
5. Since the modulation coils are typically located in the walls of the resonator they
are more proximal to the sample and can generate larger modulation fields - and
gradients - at the sample per unit current than is the case with external gradient
coils, which are mounted outside the resonator.

We Claim:
1. An improved device for electron paramagnetic resonance imaging, characterized by a
microwave bridge consisting of a source of electromagnetic radiation (12) in the
microwave region, and attenuation and phase shift elements, the output of the said
source (12) is connected to one arm of a circulator or magic tee (13), another arm of
the said magic tee (13) is coupled to a resonator (14) through an iris coupling, a third
arm being connected to a microwave detector, e.g. diode detector (16), the output of
the said microwave detector is connected to one input of a phase sensitive detector
(PSD) (17), second input of the said phase sensitive detector is connected to one output
of a high amplitude modulator (15),for producing large field modulation amplitudes of at
least 20 Gauss, second output of the said modulator (15) is connected to the
modulation coils to get rotated externally and associated with the said resonator (14),
the output of the said PSD (17) being connected to an analog-to-digital converter (ADC)
(18), output of the said ADC is connected to a computer (19), the said resonator (14)
being placed in the center of a magnetic field between the North pole and South pole of
a magnet (20).
2. An improved device, as claimed in claim 1, wherein the source of electromagnetic
radiation used is selected from klystron, Gunn diode oscillator, Impact Avalanche and
Transit Time (IMPATT) diode.
3. An improved device as claimed in claims 1-2, wherein the resonator used is selected
from slow wave helical structure, dielectric resonator, cylindrical resonator, rectangular
resonator, slotted resonator.
4. An improved device for Electron Paramagnetic Resonance Imaging, substantially as
herein described with reference to the examples and drawings accompanying the
specification.

Documents:

792-del-2000-abstract.pdf

792-del-2000-claims.pdf

792-del-2000-correspondence-other.pdf

792-del-2000-correspondence-po.pdf

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

792-del-2000-drawings.pdf

792-del-2000-form-1.pdf

792-del-2000-form-19.pdf

792-del-2000-form-2.pdf

792-del-2000-form-3.pdf

792-del-2000-petition-138.pdf


Patent Number 232777
Indian Patent Application Number 792/DEL/2000
PG Journal Number 13/2009
Publication Date 27-Mar-2009
Grant Date 21-Mar-2009
Date of Filing 01-Sep-2000
Name of Patentee COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH
Applicant Address RAFI MARG, NEW DELHI-110001, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 NARAYANAN CHANDRAKUMAR CENTRAL LEATHER RESEARCH INSTITUTE, ADYAR, CHENNAI-600 020, INDIA.
2 KASSEY VICTOR BABU CENTRAL LEATHER RESEARCH INSTITUTE, ADYAR, CHENNAI-600 020, INDIA.
3 VISALAKSHI VIJAYARAGAVAN CENTRAL LEATHER RESEARCH INSTITUTE, ADYAR, CHENNAI-600 020, INDIA.
PCT International Classification Number G01V 3/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA