WO2001020306A9 - System and method for tomographic imaging of dynamic properties of a scattering medium - Google Patents
System and method for tomographic imaging of dynamic properties of a scattering mediumInfo
- Publication number
- WO2001020306A9 WO2001020306A9 PCT/US2000/025155 US0025155W WO0120306A9 WO 2001020306 A9 WO2001020306 A9 WO 2001020306A9 US 0025155 W US0025155 W US 0025155W WO 0120306 A9 WO0120306 A9 WO 0120306A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- source
- energy
- medium
- imaging head
- detector
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
Definitions
- the invention relates to a system and method for tomographic imaging of dynamic properties in of a scattering medium, which may have special application to medical imaging, and in particular to systems and methods for tomographic imaging using near infrared energy to image time variations in the optical properties of tissue.
- Optical tomography yields insights into anatomy and physiology that are unavailable from other imaging methods, since the underlying biochemical activities of physiological processes almost always leads to changes in tissue optical properties. For example, imaging blood content and oxygenation is of interest. Blood shows prominent absorption spectra in the NIR region and vascular dynamics and blood oxygenation play a major role in physiology/pathology. However, cross-sectional or volumetric imaging of dynamic features in large tissue structures is not extractable with current optical imaging methods. At present, whereas a variety of methods involving imaging and non-imaging modalities are available for assessing specific features of the vasculature, none of these assess measure dynamic properties based on measures of hemoglobin states.
- vascular architecture involving larger vessels can be provided using x-ray enhanced contrast imaging or MR angiography.
- MR angiography x-ray enhanced contrast imaging
- These methods are insensitive to hemoglobin states and only indirectly provide measures of altered blood flow.
- the latter is well accomplished, in the case of larger vessels, using Doppler ultrasound, and for near-surface microvessels by laser Doppler measurements, but each is insensitive to variations in tissue blood volume or blood oxygenation. Ultrasound measurements are also limited by their ability to penetrate bone.
- Other methods are available, (e.g., pulse volume recording, magnetic resonance (MR) BOLD method, radioscintigraphic methods), and each is able to sample, either directly or indirectly, only a portion of the indicated desired measures.
- MR magnetic resonance
- FIG. 3 is a perspective view of a servo-motor apparatus useful in this invention to illuminate a number of fiber bundles with a single energy source;
- FIG. 6 is one embodiment for the source detector arrangement on the imaging head shown in FIG. 5;
- FIG. 8 is a block diagram of a detector channel useful in practicing the invention
- FIG. 9 is a graphical representation of one implementation of a timing scheme used in the system of FIG.1;
- FIG. 10 is a diagram illustrating the sequence of certain events in a multiple channel embodiment of the invention.
- FIG. 11 is a schematic illustration of the physical arrangement of multiple detector channels used in a preferred embodiment of the invention.
- FIG. 12 is a circuit diagram of one detector channel used in FIG. 11; and FIG. 13 is a circuit diagram of one implementation of the lock-in module used in FIG 12.
- the objective of the invention is to provide a system and method capable to extract dynamics in properties of a scattering medium.
- the use of the invention's system and method has several applications including, but not limited to, medical imaging applications.
- medical imaging applications focus on tomographic imaging the dynamic properties of hemoglobin states and tissue using optical tomography, with an imaging source generating multiple wavelengths in the NIR region, it is appreciated that the invention is applicable to any medium that is able to scatter the propagating energy from any energy source, including external energy sources such as those sources located outside the medium and/or internal sources such as those energy sources located inside the medium.
- other media includes, but are not limited to, medium from mammals, botanical life, aquatic life, or invertebrates; oceans or water masses; foggy or gaseous atmospheres; earth strata; industrial materials; man-made or naturally occurring chemicals and the like.
- Energy sources include, but are not limited to, non-laser optical sources like LED and high-pressure incandescent lamps and lasers sources such as laser diodes, solid state lasers such as titanium-sapphire laser and ruby laser, dye laser and other electromagnetic sources, acoustic energy, acoustic energy produced by optical energy, optical energy, and any combinations thereof.
- the means to detect the signal produced by the energy source is not limited to photodiode implementation discussed in one of the preferred embodiments further described herein.
- Other detectors can be used with the principles of the present invention for the purpose of tomographic imaging the dynamic properties of a medium.
- detectors include for example, but are not limited to, photo-diodes, PIN diodes (PIN), Avalanche Photodiodes (APD), charge couple device (CCD), charge inductive device (CID), photo-multiplier tubes (PMT), multi-channel plate (MCP),acoustic transducers and the like.
- the modification in the imaging head allows accommodation of different size targets (e.g., breast); the stabilization of the target against motion artifacts; conforming the target to a simple well-defined geometry; and knowledge of source and detector positioning on or about the target. All of the enumerated features listed above for the imaging head is crucial for accurate image reconstruction. Additionally, the present invention uses detector circuitry that allows quick adaptation of the measurement range to the signal strength thereby increasing the over-all dynamic range. "Dynamic range" for the purposes of this description means the ratio between the highest and lowest detectable signal. This makes the circuitry suitable for use with source-detector distances that can vary significantly during the data collection, thereby allowing fast data acquisition over wide viewing angles.
- the system of the present invention can also be operated using detector channels of low- dynamic range (e.g., 1:1000) when detector fibers of a fixed distance from the source are being used for the measurement (e.g., the detector opposite the source).
- detector channels of low- dynamic range e.g., 1:1000
- the data collection scheme of the present invention disclosed herein provides time-series of raw data sets that provide useful information about dynamic properties of the scattering medium without any further image reconstruction. For example, by displaying the raw data in a color mapping format, features can be extracted by sole visual inspection.
- analysis algorithms of various types such as, but not limited to, linear and non-linear time-series analysis or pattern recognition methods can be applied to the series of raw data. The advantage of using these analytical methods is the improved capability to reveal dynamic signatures in the signals.
- image reconstruction methods may be applied to the sets of raw data thereby providing time series of cross-sectional images of the scattering medium.
- analysis methods of various types such as, but not limited to, linear and non-linear time-series analysis, filtering, or pattern recognition methods can be applied.
- the advantage of using such analysis is the improved extraction of dynamic features and cross-sectional view, thereby increasing diagnostic sensitivity and specificity.
- the invention reveals measurements of real-time spatial temporal dynamics.
- an image of dynamic optical properties of scattering medium such as, but not limited to, the vasculature of the human body in a cross- sectional view.
- the technology employs low cost, compact instrumentation that uses non-damaging near infrared optical sources and features several alternate imaging heads to permit investigation of a broad range of anatomical sites.
- the principles of the present invention can be used in conjunction with contrast agents such as absorbing and fluorescent agents.
- the present invention allows the cross-sectional measurements of changes in optical properties due to variations in temperature. The advantage of this variant is seen, but not restricted to, the use of monitoring cryosurgery.
- a system using the modified instrumentation and described methods of the instant invention is capable of producing cross-sectional images of real-time events associated with vascular reactivity in a variety of tissue structures (e.g., limbs, breast, head and neck).
- tissue structures e.g., limbs, breast, head and neck.
- Such measurements permit an in-depth analysis of local hemodynamic states that can be influenced by a variety of physiological manipulations, pharmacological agents or pathological conditions.
- Measurable physiological parameters include identification of local dynamic variations in tissue blood volume, blood oxygenation, estimates of flow rates, and tissue oxygen consumption. It is specifically noted that measurements of several locations on the same medium can be taken. For example, measurements may be taken of the leg and arm areas of a patient at the same time. Correlation of data between the different locations is available using the methods described herein.
- the invention also provides both linear and non-linear time series analysis to reveal site specific functionality of the various components of the vascular tree.
- the response characteristics of the major veins, arteries and structures associated with the microcirculation can be evaluated in response to a range of stimuli.
- FIG. 1 illustrates one embodiment of the invention. Shown is a system 100 comprising medium 102.
- the medium can be any medium in which the propagation of the used source energy is strongly affected by scattering.
- a source module 101 energy is directed to the medium 102 from which the exiting energy is measured by means of detector 106, further discussed below.
- detector 106 there is a variety of sources, media, and detectors that may be used with the principles of the present invention. The following is a discussion of a sampling of such elements with the intention to describe how the invention is realized. In no way are these examples meant, nor do they intend to limit the invention to these - implementations. A variation of elements as described herein may also utilize the principles of the present invention.
- measurements of dynamics in the optical properties of the medium is accomplished by using optical source energy and performing rapid detection of the acoustic energy created by absorption processes in the medium. This can be implemented using both pulsed and harmonic modulated light sources, the latter allowing for lock-in detection.
- Detectors can be, but are not limited to, piezo-electric transducers such as PZT crystals or PVDF foils.
- a timing and control facility 104 is used to coordinate source and detector operation. This coordination is further described below.
- a device 116 provides acquisition and storage of the data measured by the detector 106.
- control and timing of the system's components is provided by a computer, which includes a central processor unit (CPU), volatile and non- volatile memory, data input and output ports, data and program code storage on fixed and removable media and the like. Each main component is described in greater detail below.
- FIG. 2 illustrates another implementation of a preferred embodiment of the present invention. Shown is a system and method that incorporates at least one wavelength measurement. Depending upon the implementation, this measurement is accomplished by alternately coupling light from diode lasers into transmitting fibers arranged in a circular geometry.
- a system 200 includes an energy source, which in this implementation includes one or more laser 101.
- a reference detector 202 is used to monitor the actual output power of laser 101 and is coupled to a data acquisition unit 116.
- Such laser may be a laser diode in the NIR region.
- the laser is intensity modulated by a modulation means 203 for providing means of separation of background energy sources such as daylight.
- the modulation signal is also send to a phase shifter 204 whose purpose is described further below.
- the light energy generated by the laser 101 is directed into an optical de-multiplexing device 300 further discussed in detail below. Using a rotating mirror 305, the light is being directed into one of several optical source fiber bundles 306 that are used to deliver the optical energy to the medium 102.
- the measuring head 206 comprises the common end of a bifurcated optical fiber bundle, whose split ends are formed by the source fiber bundle 306 and detector fiber bundle 207.
- Source fiber bundle 306 and detector fiber bundle 207 form a bulls eye geometry at the common end with the source fiber bundle in the center. In other embodiments, source and detector bundles are arranged differently at the common end (e.g., reversed geometry or arbitrary arrangement of the bundle filaments).
- the common end of a bifurcated optical fiber bundle preferably comes in contact with the medium, however, this embodiment is not limited to contact with the medium. For example, the common ends may simply be disposed about the medium.
- the signal is transmitted from the detector fiber bundle 207 to a detector unit 106 that comprises at least one detector channel 205 further described herein..
- Unit 300 Light from laser 101 is transmitted to unit 300 by means of transmitting optics 303 including, but not limited to, fiber optics and free propagating beams. Further beam shaping optics 301 may be used to optimize in -coupling efficiency into the transmitting fibers. Units 303 and 301 are under mechanical fine adjustment in their position with respect to the mirror 309.
- the additional pad would have similar functions as the pad previously described and would have optical fiber bundles 503, flexible pad 505, and bifurcated optical fiber bundle ends 501 similar to the previous pad described.
- the array itself can be deformed to conform to the surface of a curved medium to be imaged (e.g. portion of the torso).
- the deformable array optical energy source and receiver design includes, depending on the implementation, a 7 x 9 array (63 total bundles) of optical fiber bundles as illustrated in FIG 6. In one variant, each bundle is typically 3 mm in diameter.
- the geometry of the illumination array is not arbitrary.
- the design shown in Figure 6 as an exemplary illustration has been configured, as have other implementations, to minimize the subsequent numerical effort required for data analysis while maximizing the source-density covered by the array.
- the fiber bundles are arranged in an alternating pattern as described by FIG. 6 and shown here with the symbols "X" and "0".
- a pattern of 00X000X00, X000X000X can be used on the imaging head.
- 'X' denotes a source/receiver fiber bundle
- '0' is a receiver only a receiver or detector fiber bundle.
- the design allows for the independent solution of two dimensional (2-D) image recovery problems from an eighteen (18) point source measurement.
- a composite three dimensional (3-D) image can be computed from superposition of the array of 2-D images oriented perpendicular to the target surface.
- Another advantage of this geometry is that it readily permits the use of parallel computational strategies without having to consider the entire volume under examination.
- the advantage of this geometry is that each reconstruction data set is derived from a single linear array of source-detector fibers, thereby enabling solution of a 2-D problem without imposing undue physical approximations.
- the number of source- detector fibers belonging to an array can be varied. Scan speeds attainable with the 2-D array illustrated in FIG 6 are the same as for other imaging heads with 2-D arrays since the scan speed depends only on the properties of the input coupler. Thus, faster scan speed are available for the creation of a 3-D image.
- Imaging head 700 illustrates one example of modification to the "Hoberman" geometry.
- a receptacle for the fiber bundles 701 is disposed about imaging head 700.
- Target volume 702 is where the medium would enter the imaging head in this implementation.
- This geometry is well suited for the investigation of certain tissues such as the female breast or the head.
- attachment of optical fibers to the vertices of the hemisphere allows for up a seventeen (17) source by seventeen (17) detector measurement.
- the detectors or energy receivers may be disposed about the spherical imaging head and the detectors are located on the inner aspect of the expanding imaging head.
- Additional fiber bundles can be attached to the interlocking joints, permitting up to a 49 source by 49 detector measurement.
- light collected from the target medium is measured by using any of a number of optical detection schemes.
- One embodiment uses a fiber-taper, which is bonded to a charged coupled detector (CCD) array.
- CCD charged coupled detector
- the front end of the fiber taper serves to receive light exiting from the collection fibers.
- These fibers are preferably optical fibers, but can be any means that allows the transmission and reception of signals.
- the back end of the fiber taper is bonded to a 2-D charge-coupled- detector (CCD) array.
- CCD charge-coupled- detector
- An alternate detection scheme employs an array of discrete photo detectors, one for each fiber bundle. This unit can be operated in a phase lock mode thereby allowing for improved rejection of ambient light signals and the discrimination of multiple simultaneously operated energy sources.
- the detector system uses photodiodes and a signal recovering technique involving electronic gain switching and phase sensitive detection (lock-in amplification) for each detector fiber (in the following referred to as detection or detector channels) to ensure a large dynamic range at the desired data acquisition rate.
- the phase sensitive signal recovery scheme not only suppresses electronic noise to a desired level but also eliminates disturbances given by background light and allows simultaneous use of more than one energy source. Separation of signals from simultaneously operating sources can be achieved, as long as the different signals are encoded in sufficiently separated modulation frequencies. Since noise reduction techniques are based on the reduction of detection bandwidth, the system is designed to maintain the desired rate of measurements.
- the signal After detecting the light at the optical input 801 by a photo detector 802 the signal is fed to a transimpedance amplifier 803.
- the signal is subsequently amplified by a Programmable Gain Amplifier (PGA ⁇ whose gain can be set externally by means of digital signals 814. This allows for additional gain for the lowest signal levels (e.g., in one implementation ⁇ p W-nW) thereby thereby increasing the dynamic range of the detector channel.
- PGA ⁇ Programmable Gain Amplifier
- At least one energy source is used and the signal is sent to at least one of lock-in amplifiers (LIA) 805, 809.
- Each lock-in amplifier comprises an input 808,812 for the reference signal generated by phase shifter 204 from FIG 2.
- the demodulated signal is appropriately boosted in gain by means of a programmable gain amplifier (PGA) 806, 810 in order to maximize noise immunity during further signal transmission and to improve digital resolution when being digitized.
- the gain of PGA 806, 810 is set by digital signals 815.
- a sample-and-hold circuit (S/H) 807, 811 is used for freezing the signal under digital timing by means of signal 816 for purposes described herein.
- the signal 815 is sent to 806, 810 in parallel. In one embodiment, the signal 816 is sent to 807, 811 in parallel.
- the analog signal provided by each of the channel outputs is sampled a data acquisition system 116.
- PC extension boards might be used for this purpose.
- PC extension boards also provide the digital outputs that control the timing of functions such as gain settings and sample-and- hold.
- FIG. 9 shows one improvement of the invention over other timing schemes.
- a schedule according to 905 has to be implemented.
- the implementation in FIG 9 illustrates one use of a silicon photo-diode in process 904, which can be replaced by various detectors previously mentioned.
- a time series of data is acquired for a fixed source position. After finishing this task, the source is being moved 902 with respect to the target 901 and another series of data is being collected. Measurements are being performed in this fashion for all source positions.
- Every image 903 of the resulting time series of reconstructed images are being reconstructed from data sets merged together from the data for each source position.
- This schedule does not allow real-time capture of all physiologic processes in the medium and therefore only applies to certain modes of investigation.
- the timing scheme for the invention very much improves on this situation.
- a schedule indicated by 904 is performed.
- the source position is switched fast compared to the dynamic features of interest and instantaneous multi-channel detection is performed at each source position.
- Images 903 are then reconstructed from data sets, which represent an instant state of the dynamic properties of the medium. Only one time series of full data sets (i.e., all source positions and all detector positions) is being recorded. Real time measurement of fast dynamics (e.g., faster 1 Hz) of the medium is provided by the invention.
- FIG 10 shows one embodiment of a detailed schedule and sequence of the system tasks 1001 involved in collecting data at a source position and the proceeding of this process in time 1002.
- Task 1003 is the setting of the optical de-multiplexer to a destined source position and setting the detectors to the appropriate gain settings.
- the source position is illuminated for a period of time 1004, during which the lock-in amplifiers settle 1005.
- the signal is being hold for a period of time 1007, during which all channels are being read pout by the data acquisition. It is worthwhile noticing that during reading out the S H, other tasks, like moving the optical source, setting the detector gains for the new source position, and settling of the lock-in, are being scheduled. This increases greatly the achievable data acquisition rate of the instrument.
- a Programmable Transimpedance Amplifier (PTA) 1201 is formed by an operational amplifier 1204 , resistors 1201 and 1202 and an electronic switch 1205, the latter of which is realized using a miniature relay. Other forms of electronic switches such as analog switches might be used.
- Relay 1205 is used to connect or disconnect 1203 from the circuit thereby changing the transimpedance value of 1201.
- a high-pass filter (R2, C5) is used to AC-couple the subsequent programmable gain instrumentation amplifier IC2 (Burr Brown PGA202) in order to remove DC offset.
- the board-to-board connectors for the two lock-in-modules are labeled as "slot A" 1210 and "slot B" 1212.
- the main comiector to the backplane is a 96-pole DIN plug 1220.
- FIG. 13 illustrates the electric circuit of the lock in modules 1210, 1212.
- the signal is subdivided and passed to two identical lock-in-amplifiers, each of which gets one particular reference signal according to the sources used in the experiment.
- the signal is first buffered ICl, IC7 (AD LFl 11) and then demodulated using an AD630 double-balanced mixer IC2, IC8.
- the demodulated signal passes through an active 4-pole Bessel-type filter IC3, IC4, IC 9, IC10 (Burr Brown UAF42).
- a Bessel-type filter has been chosen in order to provide fastest settling of the lock-in amplifier for a given bandwidth. Since a Bessel-filter shows only slow stopband- transition, a 4-pole filter is being used to guarantee sufficient suppression of cross talk between signals generated by different sources (i.e. of different modulation frequency).
- the filter has its 3 dB point at 140 Hz, resulting in 6 ms settling time for a step response ( ⁇ 1% deviation of actual value).
- the isolation of frequencies separated by 1 kHz is 54 dB.
- the filters are followed by a programmable gain amplifier IC5, IC 11, whose general function has been described above.
- the last stage is formed by a sample-and-hold chip (S/H) IC6, IC12 (National LF398).
- S/H sample-and-hold chip
- the phase sensitive detection can be achieved with digital methods using digital signal processing (DSP) components and algorithms.
- DSP digital signal processing
- an analog-to-digital converter is used for each detector channel thereby improving noise immunity of the signals.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
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CA002384822A CA2384822C (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
EP00964997A EP1221035B1 (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
AU75795/00A AU7579500A (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
JP2001523841A JP2003509687A (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of scattering media |
US10/088,254 US6795195B1 (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
US11/525,188 USRE41949E1 (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
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US15392699P | 1999-09-14 | 1999-09-14 | |
US60/153,926 | 1999-09-14 | ||
US15409999P | 1999-09-15 | 1999-09-15 | |
US60/154,099 | 1999-09-15 |
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WO2001020306A1 WO2001020306A1 (en) | 2001-03-22 |
WO2001020306A9 true WO2001020306A9 (en) | 2002-09-26 |
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PCT/US2000/025155 WO2001020306A1 (en) | 1999-09-14 | 2000-09-14 | System and method for tomographic imaging of dynamic properties of a scattering medium |
PCT/US2000/025136 WO2001020305A1 (en) | 1999-09-14 | 2000-09-14 | Method and system for imaging the dynamics of scattering medium |
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US (1) | USRE41949E1 (en) |
EP (2) | EP1221035B1 (en) |
JP (3) | JP2003509687A (en) |
AU (2) | AU7579300A (en) |
CA (2) | CA2384822C (en) |
WO (2) | WO2001020306A1 (en) |
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-
2000
- 2000-09-14 WO PCT/US2000/025155 patent/WO2001020306A1/en active Application Filing
- 2000-09-14 EP EP00964997A patent/EP1221035B1/en not_active Expired - Lifetime
- 2000-09-14 WO PCT/US2000/025136 patent/WO2001020305A1/en active Application Filing
- 2000-09-14 AU AU75793/00A patent/AU7579300A/en not_active Abandoned
- 2000-09-14 EP EP00964994.8A patent/EP1221034B1/en not_active Expired - Lifetime
- 2000-09-14 JP JP2001523841A patent/JP2003509687A/en active Pending
- 2000-09-14 AU AU75795/00A patent/AU7579500A/en not_active Abandoned
- 2000-09-14 US US11/525,188 patent/USRE41949E1/en not_active Expired - Lifetime
- 2000-09-14 JP JP2001523840A patent/JP5047432B2/en not_active Expired - Fee Related
- 2000-09-14 CA CA002384822A patent/CA2384822C/en not_active Expired - Fee Related
- 2000-09-14 CA CA2384813A patent/CA2384813C/en not_active Expired - Fee Related
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2011
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Also Published As
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EP1221035A1 (en) | 2002-07-10 |
JP2003509687A (en) | 2003-03-11 |
WO2001020305A1 (en) | 2001-03-22 |
CA2384813C (en) | 2014-01-21 |
JP2003527883A (en) | 2003-09-24 |
JP5047432B2 (en) | 2012-10-10 |
EP1221034A1 (en) | 2002-07-10 |
JP2012053053A (en) | 2012-03-15 |
WO2001020305A9 (en) | 2002-09-26 |
EP1221035A4 (en) | 2009-07-01 |
CA2384813A1 (en) | 2001-03-22 |
USRE41949E1 (en) | 2010-11-23 |
AU7579300A (en) | 2001-04-17 |
EP1221034B1 (en) | 2013-05-22 |
CA2384822A1 (en) | 2001-03-22 |
AU7579500A (en) | 2001-04-17 |
EP1221034A4 (en) | 2009-06-24 |
EP1221035B1 (en) | 2012-05-23 |
WO2001020306A1 (en) | 2001-03-22 |
CA2384822C (en) | 2007-01-02 |
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