The invention provides a method for identifying one or more materials in a scene by determining a set of spectral vectors, called endmembers, from a data set comprised of spectra from the image data, and matching the set of endmembers to predefined library materials. The image data of the scene is captured with a sensor, and comprises a plurality of spectra. The method applies an iterative mathematical criterion, termed residual minimization, to find the endmembers. The first endmember may be selected based on the largest mean square value or the largest mean magnitude value. Subsequent endmembers are determined by calculating weighting factors, such that the weighting factors are non-negative and the calculated vector differences, or residuals, generate the smallest error metric. The error metric is dependent upon the vector difference between two spectra in the image data set, and may be the mean squared vector difference between two spectra.

Endmembers are spectra that are chosen to represent the most "pure" surface materials from which the pixels in a spectral image are composed. Mathematically, they are basis spectra whose physically constrained linear combinations match the pixel spectra (to within some error tolerance), but which themselves cannot be represented by such linear combinations. "Physically constrained" means constrained by positivity, at least. Endmembers that represent radiance spectra must satisfy the positivity constraint. Other physically-based constraints may be imposed, such as sum-to-unity (i.e., the pixels are weighted mixtures of the endmembers) or sum-to-unity or less (i.e., the pixels are weighted mixtures of the endmembers plus "black"). The latter constraint is common for reflectance spectra. The invention allows selection of any of these constraints.
There are two different categories of endmembers and several different methods and algorithms for finding them. The first category consists of endmembers that do not necessarily correspond to specific pixels in the image. For example, they may represent materials of a purer composition than occur in the scene. Such spectra might be obtained from a library of laboratory-measured reflectances for a variety of materials that might be present. Alternatively, the endmembers may represent cluster averages, which match many spectra well but none exactly.
The invention (sometimes termed "SMACC" herein) relates primarily to the second category of endmembers, which are actual pixels in the image. There are several well-known algorithms for finding these endmembers. IDL's ENVI software contains a method based on a "Pixel Purity Index" [ENVI Users Guide, Research Systems, Inc., 2001] and supervised N-dimensional visualization. This method is not automated (it requires manual operation by an analyst) and is fairly time-consuming. Another method, called N-FINDR [http://www.sennacon.com/nfindr/], chooses endmembers based on a maximum-simplex-volume criterion, and is fully automated and reasonably fast.
There are many uses of endmembers, including classification, detection and data compression. The endmembers can be used to identify unique materials in the scene, and thus can be input to classification routines. They can also be used in a constrained least-squares unmixing routine to find targets and their pixel fill fraction, as an alternative to matched filtering. If the number of spectral channels is large, the endmember abundances are sparse (most values are zero), so the abundance image represents an efficient compression of the original data cube. Upon matching the endmembers to library materials, the abundances define the surface material composition of the scene. This enables one to estimate various physical properties, such as surface reflectance at wavelengths not originally measured.

Process for finding endmembers in a data set


The present invention relates to tissue-supporting medical devices and drug delivery systems, and more particularly to tubular flexible stents that are implanted within a body lumen of a living animal or human to support the organ, maintain patency and/or deliver drugs or agents. The tubular flexible stent has a cylindrical shape defining a longitudinal axis and includes a helical section having of a plurality of longitudinally oriented strut members and a plurality of circumferentially oriented hinge members connecting circumferentially adjacent strut members to form a band. The band is wrapped about the longitudinal axis in a substantially helical manner to form a plurality of helical windings. At least one connector member extends between longitudinally adjacent helical windings of the band.

1. Field of the Invention
The present invention relates to tissue-supporting medical devices and drug delivery systems, and more particularly to expandable devices that are implanted within a body lumen of a living animal or human to support the organ, maintain patency and/or deliver drugs or agents.
2. Summary of the Related Art
In the past, permanent or biodegradable devices have been developed for implantation within a body passageway to maintain patency of the passageway and/or locally deliver drug or agent. These devices are typically introduced percutaneously, and transported transluminally until positioned at a desired location. These devices are then expanded either mechanically, such as by the expansion of a mandrel or balloon positioned inside the device, or expand themselves by releasing stored energy upon actuation within the body. Once expanded within the lumen, these devices, typically referred to as stents, become encapsulated within the body tissue and remain a permanent implant.
Known stent designs include monofilament wire coil stents (U.S. Pat. No. 4,969,458); welded metal cages (U.S. Pat. Nos. 4,733,665 and 4,776,337); and, most prominently, thin-walled metal cylinders with axial slots formed around the circumference (U.S. Pat. Nos. 4,733,665, 4,739,762, and 4,776,337). Known construction materials for use in stents include polymers, organic fabrics and biocompatible metals, such as, stainless steel, gold, silver, tantalum, titanium, cobalt chromium and shape memory alloys such as Nitinol.
U.S. Pat. Nos. 4,733,665, 4,739,762, and 4,776,337 disclose expandable and deformable interluminal vascular grafts in the form of thin-walled tubular members with axial slots allowing the members to be expanded radially outwardly into contact with a body passageway. After insertion, the tubular members are mechanically expanded beyond their elastic limit and thus permanently fixed within the body. The force required to expand these tubular stents is proportional to the thickness of the wall material in a radial direction. To keep expansion forces within acceptable levels for use within the body (e.g., 5-10 atm), these designs must use very thin-walled materials (e.g., stainless steel tubing with 0.0025 inch thick walls). However, materials this thin are not visible on conventional fluoroscopic and x-ray equipment and it is therefore difficult to place the stents accurately or to find and retrieve stents that subsequently become dislodged and lost in the circulatory system.
Further, many of these thin-walled tubular stent designs employ networks of long, slender struts whose width in a circumferential direction is two or more times greater than their thickness in a radial direction. When expanded, these struts are frequently unstable, that is, they display a tendency to buckle, with individual struts twisting out of plane. Excessive protrusion of these twisted struts into the bloodstream has been observed to increase turbulence, and thus encourage thrombosis. Additional procedures have often been required to attempt to correct this problem of buckled struts. For example, after initial stent implantation is determined to have caused buckling of struts, a second, high-pressure balloon (e.g., 12 to 18 atm) would be used to attempt to drive the twisted struts further into the lumen wall. These secondary procedures can be dangerous to the patient due to the risk of collateral damage to the lumen wall.
In addition, many of the known stents display a large elastic recovery, known in the field as "recoil," after expansion inside a lumen. Large recoil necessitates over-expansion of the stent during implantation to achieve the desired final diameter. Over-expansion is potentially destructive to the lumen tissue. Known stents of the type described above experience recoil of up to about 6 to 12% from maximum expansion.
Large recoil also makes it very difficult to securely crimp most known stents onto delivery catheter balloons. As a result, slippage of stents on balloons during interlumenal transportation, final positioning, and implantation has been an ongoing problem. Many ancillary stent securing devices and techniques have been advanced to attempt to compensate for this basic design problem. Some of the stent securing devices include collars and sleeves used to secure the stent onto the balloon.
Another problem with known stent designs is non-uniformity in the geometry of the expanded stent. Non-uniform expansion can lead to non-uniform coverage of the lumen wall creating gaps in coverage and inadequate lumen support. Further, over expansion in some regions or cells of the stent can lead to excessive material strain and even failure of stent features. This problem is potentially worse in low expansion force stents having smaller feature widths and thicknesses in which manufacturing variations become proportionately more significant. In addition, a typical delivery catheter for use in expanding a stent includes a balloon folded into a compact shape for catheter insertion. The balloon is expanded by fluid pressure to unfold the balloon and deploy the stent. This process of unfolding the balloon causes uneven stresses to be applied to the stent during expansion of the balloon due to the folds causing the problem non-uniform stent expansion.
It is desirable to provide flexibility in stents to facilitate introduction of the stent into vessels that are difficult to reach. Often, however, characteristics of the stent that provide longitudinal flexibility, which is desirable when introducing the stent into the vessel, can be disadvantageous in terms of keeping the stent in an expanded condition. For example, stents formed from interconnected rings with closed cell structures or generally diamond-shaped cells are typically less flexible than stents formed from one or more helices, but are usually more uniformly and consistently expandable than helical stents. It is desirable to provide a stent with substantial flexibility that is adapted to be expanded in a uniform and consistent fashion.
In WO 03/015664, which is incorporated by reference, a stent having interconnected struts with openings for drug delivery is disclosed. However, elements for bridging the struts are generally thinner and spaced further apart than the struts. Thus, for such drug-eluting stents, the bridging element can provide an area of reduced or less consistent drug delivery. It is desirable to provide a drug-eluting stent in which areas of reduced or less consistent drug delivery can be reduced.

This patent is subject to a terminal disclaimer.


A wheel alignment measuring device using a body center line of a vehicle includes: front laser sensors provided at both sides of a front of a workbench on which the vehicle is disposed to measure positions of side panels each provided at both sides of a front of the vehicle; rear laser sensors at both sides of a rear of the workbench to measure positions of the side panels each provided at both sides of a rear of the vehicle; and a measuring unit configured to connect a center point A of a connection line connecting two points of a front of the side panels measured by the front laser sensors and a center point B of a connection line connecting two points of a rear of the side panels measured by the rear laser sensors to obtain a body center line C of the vehicle.

1. Field of Invention
The present invention relates to a wheel alignment measuring device for a vehicle measuring a wheel alignment based on a body center line in order to improve straight driving performance of the vehicle when a driving drift, unbalanced wear of a tire, deflected driving, or the like, occur, and a measuring system and a measuring method using the same.
2. Description of Related Art
In general, a large-sized bus measures and adjusts contact-type wheel alignment and deflection in order to improve straight driving performance. That is, the wheel alignment measurement measures the wheel alignment using wheel clamps 30 and 3D cameras 40 installed on wheel surfaces of a steering shaft 10 and a driving shaft 20 as shown in FIG. 1, and the deflection measurement measures a distance by ultrasonic sensors 60 while a vehicle is driven by roll tester rollers 50 in a roll test process and calculates a displacement difference between a front part 70 and a rear part 80 of a vehicle outer plate using the measured distance, as shown in FIG. 2.
Meanwhile, a wheel alignment measuring device for the vehicle has been disclosed in Korean Utility Model Registration No. 20-0324989.
However, the wheel alignment measuring device according to the related art may have quality problems such as a driving drift, deflected driving, and the like due to being out-of-square when offsets of the steering shaft 10 and the driving shaft 20 occur at the time of the measurement and adjustment of the wheel alignment, and a problem that it is difficult to accurately measure a deflected amount due to occurrence of left and right movements of a roller caused by characteristic of an automatic centering adjustment type roller bearing 50 used in the roll tester at the time of the measurement of the deflection.
The information disclosed in this Background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Wheel alignment measuring device for vehicle and measuring system and measuring method using the same


A transducer comprised of a resonator and a piezoelectric crystal for cleaning single items such as semiconductor wafers and flat panel displays. The resonator is an elongated piece of material having a cross section that is trapezoidal in shape. The parallel sides of the trapezoid form the top and bottom ends of the resonator and the nonparallel sides of the trapezoid focus the acoustic energy on the bottom end of the resonator.

1. Technical Field
The present invention relates to systems that use acoustic energy in the frequency range around one megahertz to clean objects and more particularly to a system for cleaning single objects that uses a crystal attached to a resonator having an elongated wedge shape.
2. Background Information
It is well-known that sound waves in the frequency range of 0.4 to 2.0 megahertz (MHz) can be transmitted into liquids and used to clean particulate matter from damage sensitive substrates. Since this frequency range is predominantly near the megahertz range, the cleaning process is commonly referred to as megasonic cleaning. Among the items that can be cleaned with this process are semiconductor wafers in various stages of the semiconductor device manufacturing process, disk drive media, including compact disks and optical disks, flat panel displays and other sensitive substrates.
Megasonic acoustic energy is generally created by exciting a crystal with radio frequency AC voltage. The acoustical energy generated by the crystal is passed through an energy transmitting member (a resonator) and into a cleaning fluid. Frequently, the energy transmitting member is a wall of the vessel that holds the cleaning fluid, and a plurality of objects are placed in the vessel for cleaning. For example, U.S. Pat. No. 5,355,048, discloses a megasonic transducer comprised of a piezoelectric crystal attached to a quartz window by several attachment layers. The megasonic transducer operates at approximately 850 KHz. Similarly, U.S. Pat. No. 4,804,007 discloses a megasonic transducer in which energy transmitting members comprised of quartz, sapphire, boron nitride, stainless steel or tantalum are glued to a piezoelectric crystal using epoxy.
It is also known that megasonic cleaning systems can be used to clean single objects, such as individual semiconductor wafers. For example, U.S. Pat. No. 6,021,785 discloses the use of a small ultrasonic transmitter positioned horizontally adjacent to the surface of a rotating wafer. A stream of water is ejected onto the surface of the wafer and used to both couple the acoustic energy to the surface of the disk for sonic cleaning and to carry away dislodged particles. Similarly, U.S. Pat. No. 6,039,059 discloses the use of a solid cylindrically-shaped probe that is placed close to a surface of a wafer while cleaning fluid is sprayed onto the wafer and megasonic energy is used to excite the probe. In another example, U.S. Pat. No. 6,021,789 discloses a single wafer cleaning system that uses a plurality of transducers arranged in a line. A liquid is applied to a surface of the wafer and the transducers are operated so as to produce a progressive megasonic wave that carries dislodged particles out to the edge of the wafer.
A problem with megasonic transducers of the prior art is that the acoustic power that can be generated by the megasonic transducer in the cleaning solution is limited to about 10 watts per cm2 of active piezoelectric surface without supplying additional cooling to the transducer. For this reason, most megasonic power sources have their output limited, require liquid or forced air cooling or are designed for a fixed output to the piezoelectric transducer or transducers. Typically, fixed output systems are limited to powers of 7-8 watts/cm2. This limits the amount of energy that can be transmitted to the cleaning solution. If more power is applied to the transducer, the crystal can heat up to the point where it becomes less effective at transmitting energy into the cleaning solution. This is caused either by nearing the maximum operating temperature of the crystal or, more often, by reaching the failure temperature of the material used to attach the crystal to the energy transmitting member.

Megasonic transducer with focused energy resonator


A MIM capacitor includes a dielectric cap that enhances performance and reduces damage to MIM insulators during manufacture. A cavity is formed in an insulative substrate, such as a back end of line dielectric layer, and a first metal layer and an insulator layer are conformally deposited. A second metal layer may be deposited conformally and/or to fill a remaining portion of the cavity. The dielectric cap may be an extra layer of insulative material deposited at ends of the insulator at an opening of the cavity and may also be formed as part of the insulator layer.

The present invention relates to microfabrication of semiconductor devices, and, more specifically, to structures and fabrication methods of metal-insulator-metal (MIM) capacitors.
Current MIM capacitors are limited in size because they typically include two metal plates with an insulator between the plates. In such a configuration, the plates must have a significant surface area to achieve desired capacitances. One solution for this has been to develop a MIM capacitor oriented transversely to a surface of surrounding substrate, such as an insulated through-silicon-via (TSV) type MIM. However, the via configuration imposes limits on efficiency and capacitance for a given configuration.

Metal insulator metal (MIM) capacitor structure


A pharmaceutical composition containing an artificial oxygen carrier, which has high oxygen carrying efficiency; and has a required colloid osmotic pressure, an appropriate crystalloid osmotic pressure, pH, and electrolyte balance. The composition is prepared by appropriately adding at least one substance selected from the group consisting of a compound capable of providing a colloid osmotic pressure, an electrolyte, a saccharide, an amino acid, an antioxidant, a pH adjuster, and an isotonizing agent to a preparation including a liposome-encapsulated hemoglobin in which a hemoglobin is encapsulated in a liposome or to a preparation including a conjugate of a porphyrin-iron complex and albumin.

It is known that a plasma protein, which is a plasma colloid, plays an important role in maintaining the amount of blood in blood vessels of a living body. Therefore, up to now, techniques for fluid replacement with a plasma expander having a colloid osmotic pressure approximately equal to that of blood of a living body have been applied for recovering hemorrhagic shock of a patient. However, in the case where a patient bleeds in an amount of 30% or more of the circulating blood, oxygen is insufficiently provided to peripheral tissues, so that the patient requires administration of an oxygen carrier in addition to a plasma expander.
Conventionally, natural blood containing natural erythrocytes or an erythrocyte concentrated solution has been used as such an oxygen carrier. However, in order to avoid blood clot caused by antigen-antibody reaction, it is required that the blood type of a donor matches that of a receptor and cross-compatibility is performed when in use. In addition, the effective storage period of such natural blood or erythrocyte concentrated solution is as short as 3 weeks (4° C.). Frozen blood capable of long-term storage has problems such as high cost and occurrence of hemolysis by osmotic pressure shock when using it. Moreover, occurrence of infectious diseases such as hepatitis and acquired immunodeficiency syndrome was also a concern.
In order to solve the aforementioned problems, the following studies have already been disclosed: a study on an artificial oxygen carrier composed of a fluorocarbon emulsion (JP 60-33367); a study on a blood substitute for extending retention time of hemoglobin (such as human hemoglobin, bovine hemoglobin, and recombinant hemoglobin, hereinafter abbreviated to Hb), which is a heme protein having functions of adsorbing and desorbing oxygen reversibly and of dissociation, in circulating blood by binding polyethylene glycol (hereinafter abbreviated to PEG) or the like to hemoglobin for modification (JP 2-6337); or the like.
However, the oxygen carrying ability of the artificial oxygen carrier composed of a fluorocarbon emulsion depends on a physical oxygen dissolving phenomenon in fluorocarbon. Therefore, the oxygen carrying ability is insufficient. A blood substituent in which Hb binds to PEG or the like also has a problem of insufficient hemoglobin retention time.
The development of an oxygen infusion using Hb such as intramolecular crosslinking Hb, water-soluble polymer bound Hb, or intermolecular crosslinking polymerization Hb has been advanced. However, the oxygen infusion has been found to have various side effects caused by the non-cell structure.
Reasons that Hb is naturally encapsulated in erythrocyte membrane are shown in the following items:                1) to enable controlling a colloid osmotic pressure by being encapsulated by erythrocyte membrane because the colloid osmotic pressure of an Hb solution exceeds a physiological value when the Hb concentration is 5% or more;        2) to suppress the side effects by encapsulating hemoglobin having high physiological activity in membrane;        3) to retain various phosphate compounds or a glycolysis/reductase system for maintaining Hb functions such as oxygen affinity and stability of an oxygen complex in the same system; and        4) to have an advantage that a hemocyte dispersed system, which is a non-Newtonian fluid, shows a physiological function by distinctive flow form when circulating it in the body (particularly peripheral blood vessels).
Considering such primary roles of erythrocyte structure, it is clear that a dispersion system containing particles formed by encapsulating Hb in a capsule is suitable as the oxygen infusion.
On the other hand, it has been discovered that a phospholipid that is a biological component forms a vesicle structure independently, and many institutes have made studies on a hemoglobin vesicle since Djordjevich and Miller started researches on a hemoglobin vesicle using a liposome composed of phospholipid/cholesterol/fatty acid. The use of the hemoglobin vesicle has advantages in that 1) natural hemoglobin can be used without treatment, 2) the side effects caused by hemoglobin can be suppressed, 3) the viscosity, colloid osmotic pressure, or oxygen affinity can be adjusted to an arbitrary value, and 4) the retention time of blood in the body can be extended.
Various researches have been done for a liposome-encapsulated hemoglobin in which hemoglobin is encapsulated inside the layer of a liposome composed of lipid bilayer membrane (JP 52-151718, JP 58-183625, and JP 61-37735). However, a suspension of such a liposome-encapsulated hemoglobin has an extremely low colloid osmotic pressure, so that the effect of maintaining or increasing the circulating blood amount cannot be expected even when the suspension is administered to the blood vessel of a living body.
As alternatives to overcome the aforementioned defects, there has been disclosed artificial blood having both an oxygen carrying ability and a plasma expanding effect, which is formed by suspending a liposome-encapsulated hemoglobin in an aqueous solution of a plasma expander (U.S. Pat. No. 4,133,874 and JP 4-5242).
However, for the artificial blood disclosed in U.S. Pat. No. 4,133,874, the liposome-encapsulated hemoglobin tends to aggregate in the aqueous solution of the plasma expander. Therefore, the viscosity of the suspension becomes high, so that the suspension has difficulty in intravenous administration and there is a danger of the liposome aggregates causing embolization in a blood vessel.
In order to suppress an interaction between a hemoglobin vesicle and a protein in blood, the artificial blood disclosed in JP 4-5242 suppresses an interaction between a hemoglobin vesicle and a plasma expander by using an oxygen carrier in which PEG is bound to the hemoglobin vesicle surface (i.e., phospholipid) (JP 2-149512 or JP 3-218309).
However, it is known that when a water-soluble polymer such as PEG (synonymous with polyoxyethylene) is bound to a diacyl phospholipid such as phosphatidylethanolamine that is a major cell membrane component of a general living organism, the diacyl phospholipid bound to the water-soluble polymer is desorbed from a phospholipid bilayer membrane vesicle (J. R. Silvius and M. J. Zuckermann. Biochemistry, 32, 3153, 1993 and JP 2001-64383, paragraph 0004).
A pharmaceutical composition containing the aforementioned artificial oxygen carrier had the following problems. The administration of the composition to a living body without providing a colloid osmotic pressure causes a shock symptom. Moreover, in the case where the electrolyte balance differs from a physiological electrolyte balance, hemolysis or angiitis is caused due to angialgia when the pharmaceutical composition is administered to the living body or a difference between the crystalloid osmotic pressures. In addition, when the pH of the artificial oxygen infusion is higher than physiological pH, alkalosis is easily caused, whereas when the pH of the artificial oxygen infusion is lower than physiological pH, acidosis is easily caused.

Pharmaceutical composition containing artificial oxygen carrier


An antenna for a wireless terminal is disclosed with an antenna bushing configured to provide enhanced antenna performance. The antenna bushing includes an antenna guide portion having an upper tubular portion supporting a radiator at substantially a point of extraction from the wireless terminal. A bushing fastening portion is disposed adjacent the upper tubular portion. A signal contact point of the antenna bushing transfers an antenna signal to/from an RF circuit point of the wireless terminal. At least a portion of the signal contact point is adjacent the upper tubular portion. The configuration may reduce deleterious effects of EMI from other circuit components of the wireless terminal.

1. Technical Field
The present disclosure relates to an antenna of a wireless terminal, and an antenna bushing thereof which improves antenna performance.
2. Description of the Related Art
In recent designs of wireless terminals such as smart phones, laptops and GPS devices, an extractable antenna has been employed to handle transmission/reception at relatively lower frequency bands, e.g., UHF and VHF, and in particular, to receive digital multimedia broadcasting (DMB) signals at those bands. This extractable antenna is typically separate and independent from other, built-in antennas used for communication at higher frequencies (e.g., cellular band frequencies). The extractable antenna is typically a monopole, whip type antenna extractable from the housing of the wireless terminal, and retractable back into the housing via manual manipulation. For the extractable antenna of a general purpose or the DMB, a reception type antenna has been broadly used, and the reception type antenna requires an antenna bushing to support the monopole radiator, the antenna bushing being part of an antenna module.
One of the factors that impede antenna performance is the electromagnetic interference (EMI) which is emitted from peripheral electronic components. The EMI disturbs and affects an electronic circuit coupled to the extractable antenna. The disturbance may interrupt or limit the effective performance of the antenna. It is also well known that the EMI causes signal loss along with lowering the antenna performance.
FIG. 1 is a diagram illustrating a related art antenna bushing of a wireless terminal 5, and its structure depicted in a side view. The antenna bushing 7 is fastened to a separate boss 8 by aligning a hole 2 of a fastening portion 3 with a hole of the boss 8 and utilizing a fastening member through the two holes. The boss 8 is different from a rear cover boss 6 used for assembling the rear cover together with a front cover.
The antenna bushing 7 is composed of an upper, closed collar portion 7a, a lower, partial collar portion 7b, the fastening portion 3 and a signal contact plate 4 which makes electrical contact at a signal contact point 4′ (shaded circle) with a receiver contact point (not shown) of the wireless terminal. An antenna signal beginning point 1 is considered approximately in a central region of the closed collar portion 7a, which is where good electrical contact between the antenna bushing 7 and the antenna radiator is made. The signal contact point 4′ is located at a vertical distance below the antenna signal beginning point 1. The longer this distance is, the higher the signal loss occurring due to the EMI. Particularly, when electronic components such as an ear jack, a motor, and sensors are installed adjacent to the antenna bushing, the amount of the signal loss increases due to the negative impact of the EMI emitted from such peripheral electronic components. Accordingly, there exists a need for an antenna bushing that improves the antenna performance while reducing the signal loss and enhancing the durability of the antenna.

Antenna in wireless terminal with improved bushing


A system and method for halftoning for multi-pass rendering of an image in which different pixel locations are rendered in each pass which reduces the effects of inter-pass mis-registration errors. The method of halftoning includes restricting a substantial majority of the pixels turned on to render a tone to the minimum number of passes required to produce the tone. The halftoning method can include generating a stochastic halftone turn-on sequence and re-ordering the turn-on sequence. The halftoning method can also use error diffusion, adding a zero mean bias signal to either the image input pixels or the threshold values. The halftoning method is applicable to color or black and white rendering.

The present invention relates to a system and method of halftoning for multi-pass rendering, and more particularly to a system and method of halftoning for reducing the effects of inter-pass mis-registration in multi-pass printing.
With the advent of inexpensive digital color printers, methods and systems of digital halftoning have become increasingly important. It is well understood that most digital printers operate in a binary mode, i.e., for each tonal separation, a corresponding spot is either printed or not printed at a specified location or pixel. Digital halftoning controls the printing of tonal spots, where spatially averaging the printed spots of one or more tonal separations provides the illusion of the required continuous contone.
A common halftone technique is screening, which compares the required continuous tone level of each pixel for each separation with one of several predetermined threshold levels. The predetermined threshold levels are stored in a two-dimensional threshold array called a half tone screen. If, in any given region of the image, the required tone level is darker than the threshold halftone level, the pixel is turned on and printed. These pixels can be referred to as black pixels, even though they may be printed in color. Pixels not turned on are not printed and can be referred to as white pixels. It is understood in the art that the distribution of black pixels depends on the design of the halftone screen.
Some known inkjet printers print with multiple passes. With multi-pass printing, the image pixels are spatially partitioned into sets, or partitions, and a different partition is printed in each pass. Multi-pass printing can allow for better ink drying and can reduce the visibility of print head signature caused by deviations in the size and positioning of the printed dots.
A common multi-pass printer is a two-pass printer, though multi-pass printers can use any suitable number of passes. Two-pass printers print some of the black pixels in the first pass and the rest of the black pixels in the second pass. Often, one pass is printed in the forward direction of head traversal and the other in the reverse direction.
If the alignment or registration between the passes is near perfect, the graininess of the resulting images is largely unchanged in comparison with a printer that prints the entire image in a single pass. However, if there is mis-registration between the two passes the partitions can "beat" with each other to produce undesired textures that result in considerably increased graininess in the printed image.
Mis-registration in inkjet printers arises from mechanical positioning errors between the passes. Increasing the precision in the mechanical positioning can mitigate the problem of mis-registration. However, this solution can be costly due to the tight tolerances required particularly at high resolutions.
Mis-registration that is identical from page to page over the life of the printer can be detected a priori and compensated for electronically. However, electronic compensation of each individual printer also adds cost to printers. Also, electronic compensation cannot correct registration errors under half a pixel without excessive computation.
It is desirable to provide halftone screens, which reduce the effects of mis-registration in multi-pass printers in a highly accurate yet cost effective manner.

System and method of halftoning for multi-pass rendering


Bumps each having a pointed tip end or grooves are formed on electrodes of a chip, and they pierce wiring layers of an insulating film substrate such as an interposer so as to tear an oxide film or a contaminated layer produced on the surface of each of wiring layers. A new interface of the material is enabled to be continuously produced between the bumps and the wiring layers, thus making it possible to obtain an excellent electrical connection among them.

This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 2000-070211, filed Mar. 14, 2000, the entire contents of which are incorporated herein by reference.
1. Field of the Invention
The present invention relates to a semiconductor device using a film type thin insulating substrate as an interposer, and in particular, to a semiconductor device which is adapted to be employed in a thin semiconductor package or in antenna circuit board of an RFID (Radio Frequency Identification) device.
A semiconductor device using a film type interposer according to the prior art includes generally a semiconductor element (hereinafter referred to as a chip) having a plurality of pads, protruded bumps bonded to the pads respectively, and an interposer composed of an insulating film substrate having wiring layers formed of a patterned metal foil, the wiring layers being electrically connected to the bumps.
There are known several kinds of film type interposers which are adapted to be employed in a semiconductor device. Generally, these film type interposers are called an FPC (Flexible Printed Circuit board) and provided in such a manner that a metal foil such as a copper or aluminum foil is adhered onto an insulating polyimide film or an insulating PET film and that the metal foil is etched to provide conductive circuits composed of a large number of conductive layers.
As for the method of bonding a chip to this film substrate, there is known a bonding method wherein a metallic bump is formed on each pad of the chip and then, the chip is bonded to the film substrate by using an ACF (anisotropic conductive film).
FIG. 16A shows a perspective view of a chip according to the prior art, and FIG. 16B shows a cross-sectional view taken along the line 16B-16B of FIG. 16A. Referring to FIGS. 16A and 16B, on a peripheral region of main surface of a chip 101 made of a silicon semiconductor, there are provided a plurality of pads 102 of aluminum, on each of which a plated bump 103 by gold plating is provided. As for the method of forming this bump 103, there is known a method wherein a conductive film called a barrier metal is formed on the main surface of the chip 101, a plating mask is formed using a photoresist, and bumps are selectively formed on the barrier metal by means of electroplating, unwanted portions of barrier metal layer being subsequently removed.
FIG. 17A shows a perspective view of another example of a chip according to the prior art, and FIG. 17B shows a cross-sectional view taken along the line 17B-17B of FIG. 17A. Referring to FIGS. 17A and 17B, on a peripheral region of a surface of a chip 101 made of a silicon semiconductor, there are formed a plurality of pads 102 of aluminum, on each of which a stud bump 104 is provided. The stud bump 104 is formed through the stud bonding of an Au wire, the top surface of the resultant stud being subsequently pressed. More specifically, the stud bump 104 is formed by a method wherein an electrode called a torch rod is placed near a tip of Au wire, and a high voltage is applied between the torch rod and the tip of Au wire to generate a spark discharge therebetween, thereby heating the tip of the Au wire so as to provide a ball which is then pressed to the pad 102 of the chip, using a bonding tool having a capillary, the remainder of the Au wire being then pulled up, and the top surface of the bump thus formed being subsequently pressed to provide the bump.
FIG. 18A shows a perspective view of a film substrate wherein an ACF is adhered onto an insulating film substrate having aluminum wiring layers, and FIG. 18B shows a cross-sectional view taken along the line 18Bxe2x80x9418B of FIG. 18A. Referring to FIGS. 18A and 18B, on the surface of an insulating film substrate 105 of a polyimide film, there is formed an adhesive layer 108, on which aluminum wiring layers 106 are provided. Further, an ACF 107 is provided over the adhesive layer 108 to cover an end of each of the leads for providing the aluminum wiring layers 106.
FIG. 19A shows a perspective view of a device wherein a chip having bumps, which are attached to the chip by the method illustrated in FIGS. 16A and 16B, or in FIGS. 17A and 17B, is placed via an ACF onto an insulating film substrate, and then bonded to the insulating film substrate, thereby electrically connecting the bumps to the wiring layers of the insulating film substrate. FIG. 19B shows a cross-sectional view taken along the line 19Bxe2x80x9419B of FIG. 19A. FIG. 20 is an enlarged cross-sectional view of FIG. 19B, illustrating the bonded portion between the chip and the insulating film substrate. Referring to FIGS. 19A, 19B and 20, in the same manner as the case of bonding of a flip chip, the chip 101 having the bumps 104 is aligned with the wiring layers 106 of the insulating film substrate 105, and bonded thereto under a heated condition so as to cure the resin of the ACF 107, thereby executing not only the bonding of the chip 101 but also the electrical connection between the bumps (stud bumps) 104 and the aluminum wiring layers 106. By the way, the electrical connection between the stud bumps 104 and the aluminum wiring layers 106 is carried out through metallic particles 109 dispersed in the ACF 107.
As described above, the electrical connection between the bumps formed on the pads of chip and the insulating film substrate is realized through the metallic particles 109 added to the ACF 107. For example, in the case of FC262B (ACF, a product from Hitachi Kasei Co., Ltd.), a resin containing a main component of the FC262B is cured at a temperature of 180xc2x0 C. for about 30 seconds. Further, since a suitable amount of Ni particles having a particle size of about 5 to 20 xcexcm is contained in the FC262B as the metallic particles, the electrical connection between the aluminum wiring layers of the insulating film substrate and the bumps of the chip can be provided. Additionally, since the chip and the insulating film substrate are bonded to each other by heating and pressing, the Ni particles are enabled to thrust into the aluminum wiring layers of the insulating film substrate, thereby breaking the oxide film formed on the surface of aluminum wiring layers and making it possible to provide the electric conduction between the bumps and the aluminum wiring layers. However, it has been found through a reliability test such as a temperature cycling test that an oxide film tends to be newly formed on a surface of an easily oxidizable aluminum layer, thereby giving rise to conduction failure. Further, there is also known a paste type anisotropic conductive resin other than the aforementioned film type anisotropic conductive resin. However, since this paste type anisotropic conductive resin also contains metallic particles, problems such as the sedimentation of metallic particles would be caused to occur, thus deteriorating the yield in the electrical connection between the bumps and the aluminum wiring layers.
Next, other problems accompanied with the conventional interposer will be explained with reference to FIGS. 21 to 23.
FIG. 21 illustrates a perspective view of a conventional insulating film substrate having aluminum wiring layers on both surfaces, to which a chip is connected in the same manner as the bonding of the flip chip. FIG. 22 illustrates a cross-sectional view of an insulating film substrate having through-holes, wherein aluminum wiring layers provided on both surfaces of the substrate are connected to each other through the plated through-hole. FIG. 23 illustrates a cross-sectional view of an insulating film substrate having wiring layers on both surfaces, wherein the aluminum wiring layers are connected to each other by mechanical caulking. FIG. 21 shows a perspective view an opposite surface of an insulating film substrate 105 having wiring layers on both sides. Namely, aluminum wiring layers of the main surface of the film substrate 105, on which a chip is mounted, are partially connected to those of the opposite side through a caulking member 111. In FIG. 22, a through-hole is formed in the insulating film substrate 105 so that it penetrates through copper wiring layers 112 provided on both surfaces of the insulating film substrate 105, and plating is applied to the inner surface of the through-hole to form a plated layer 113, thereby electrically connecting both-sided copper wiring layers 112 to one another. In this case, since a plating process is required, the manufacturing cost would be greatly increased. Further, aluminum wiring layers can not be used because they are not adapted to plating. In the case of the method shown in FIG. 23, since the mechanical caulking is employed, it becomes possible to use the aluminum wiring layers 106. However, in order to perform the mechanical caulking, an area of at least 2 mm or more is required, thereby limiting the processing. welding (spot welding) may be employed in the same manner as aforementioned caulking. However, since the welding also requires an area of at least 2 mm or more, the same problem as that of the aforementioned caulking will be raised.
The present invention has been accomplished to overcome the aforementioned problems, and therefore, an object of the present invention is to provide a semiconductor device, wherein bumps each provided on an electrode of a chip are contacted to wiring layers of an insulating film substrate serving as an interposer to obtain excellent electrical connection, and wherein bumps each provided on a pad of a chip are made to pierce both-sided wiring layers or three or more wiring layers provided on an insulating film substrate, thereby accomplishing electrical connections among wiring layers.
Another object of the present invention is to provide a method of producing such a semiconductor device as mentioned above.
According to one aspect of the present invention, there is provided a semiconductor device wherein bumps, each provided on an electrode of a chip and having a sharply pointed configuration or cut grooves, are connected to wiring layers of an insulating film substrate used as an interposer while breaking an oxide film or contaminations formed on a surface of each of the wiring layers. Therefore, highly reliable electrical connection can be provided because a new phase of the material appears. Further, electrical connections among wiring layers can be obtained when the bumps pierce both-sided wiring layers, or three or more wiring layers of the film substrate.
According to another aspect of the present invention, there is provided a method of making a semiconductor device which comprises the steps of: forming a plurality of projected bumps on the pads formed on a surface of a semiconductor chip; preparing an interposer composed of an insulating film substrate having wiring layers formed by patterning of a metal foil; and bonding the bumps to the wiring layers in the form of a flip chip, thereby deforming a tip of each of bumps. The bumps may be composed of gold, and the wiring layers may be composed of aluminum. Another wiring layers may be formed on the opposite surface of the insulating film substrate, and the tip of each bump may be pierced through the insulating film substrate so that the bumps are electrically connected to the wiring layers of the opposite surface of the film substrate.
The tip of each of the bumps may be extended into the interior of the leads of the wiring layers. The bumps may be respectively formed of a stud bump or a plated bump. The tip of each of the bumps may be protruded to the opposite surface of the insulating film substrate. The tip of each of the bumps protruded from the opposite surface of the insulating film substrate may be electrically connected to the wiring layers of the insulating film substrate. The bumps may be composed of a material selected from gold, solder, copper and aluminum. The wiring layers formed on the insulating film substrate may be formed of a material selected from aluminum, copper, gold, silver and a conductive paste. The wiring layers to be formed on the surface of the insulating film substrate may be formed of an aluminum layer, while the bumps may be formed of gold. Furthermore, an adhesive or a thermosetting resin such as an under-fill resin may be interposed between the semiconductor chip and the insulating film substrate.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter.


An image (or other light) sensor has a reflective element under each light-sensing element. The reflective element is positioned to reflect incident light that passes through the light-sensing element without being absorbed, back towards the light-sensing element for a second chance at being absorbed. The present invention increases the effective quantum efficiency of each light-sensing element without having to increase the thickness of the absorption region within the light-sensing element. In one embodiment, each reflective element is a discrete mirror that is positioned within the sensor packaging adjacent to (e.g., below) the integrated image sensor. In another embodiment, each reflective element is an integral part of the integrated circuit that contains the image sensor, such as a light-reflecting region formed within the substrate below the corresponding light-sensing element.

1. Field of the Invention
The present invention relates to integrated sensors, such as CMOS image sensors.
2. Description of the Related Art
CMOS image sensors suffer from the problem that, with an indirect band-gap, a relatively thick absorption region is often needed to achieve the desired quantum efficiency (defined as the ratio of the number of collected photo-electrons (or photo-holes) to the number of incident photons). Unfortunately, at deep sub-micron technologies, the absorption regions often cannot be made thick enough, especially for longer wavelength light.
FIG. 1 is a cross-sectional view illustrating part of an image sensor according to the prior art. As shown in FIG. 1, incident light 102 enters at one side of a light-sensing element (represented as absorption region 100), within which some of the incident light is absorbed at locations 104 and the remaining light 106 exits at the opposite side. Absorption region 100 could correspond to an epi layer on the front side of a silicon wafer, where a photodiode is formed within the epi layer. Since silicon is an indirect band-gap material, the absorption coefficient of visible light in the range of 400-700 nanometers in silicon is relatively low.
One way to increase the quantum efficiency of the light-sensing element is to make absorption region 100 thicker in order to absorb a greater percentage of the incident light. For example, at a wavelength of 700 nanometers, an epi layer thickness of about 15 microns would absorb about 99% of incident photons. For longer wavelengths important in optical communications (such as the near IR, where wavelengths can extend to 1 micron), the absorption region of the light-sensing element must be made even thicker to achieve the same quantum efficiency. Unfortunately, this technique cannot be applied in deep sub-micron technologies, where the absorption regions often cannot be made thick enough to achieve the desired quantum efficiency.
According to the present invention, one or more reflective elements are positioned below the absorption regions of light-sensing elements in image sensors and the like. In these devices, light that passes through the absorption region of a light-sensing element without being absorbed is reflected by a corresponding reflective element back towards the absorption region, such that the reflected light enters the absorption region a second time, giving those reflected photons a second chance at being absorbed and thereby increasing the effective quantum efficiency of the light-sensing element. In this way, the present invention provides a technique for improving quantum efficiency without having to increase the thickness of the absorption region. As such, more efficient image sensors can be implemented, including those implemented using deep sub-micron technologies.
According to one embodiment, the present invention is a light sensor comprising (a) a light-sensing element formed on a substrate, the light-sensing element designed to generate an electrical signal in response to incident light absorbed within the light-sensing element; and (b) a light-reflecting element positioned in relation to the light-sensing element to reflect light transmitted through the light-sensing element back towards the light-sensing element to increase an effective quantum efficiency of the light-sensing element.
According to another embodiment, the present invention is a method comprising the steps of (a) forming a light-sensing element on a substrate, the light-sensing element designed to generate an electrical signal when incident light is absorbed therein; and (b) positioning a light-reflecting element in relation to the light-sensing element to reflect light transmitted through the light-sensing element back towards the light-sensing element to increase an effective quantum efficiency of the light-sensing element.

Integrated light sensors with back reflectors for increased quantum efficiency


A method and apparatus to generate a volume-panorama image based on three-dimensional (3D) volume images is provided. A method of generating a volume-panorama image includes receiving pieces of image data of one or more volume images, extracting partial regions including one or more voxels from the volume images, determining a global conversion function representing a relationship of a conversion between a second volume image of the volume images and a first volume image of the volume images, the determined global conversion function being based on a conversion function representing a relationship of a conversion between one of the extracted partial regions of the second volume image and one of the extracted partial regions of the first volume image, and generating image data of a volume image to be combined with the first volume image from image data of the second volume image based on the determined global conversion function.

1. Field
The following description relates to methods and apparatuses to generate a volume-panorama image based on volume images.
2. Description of Related Art
An ultrasonic imaging apparatus, a Computed Tomography (CT) apparatus, and a Magnetic Resonance Imaging (MRI) apparatus are examples of medical devices often used to generate a cross-sectional two-dimensional (2D) image of an inner portion of a target. These medical devices are used often in this capacity due to the relative convenience offered to a patient being scanned by these devices and the speed with which a result from the scan may be obtained. Ultrasonic imaging apparatuses transmit an ultrasonic signal toward a predetermined point of the inner portion of the target and obtain an image associated with the inner portion of the target based on information contained in an ultrasonic signal reflected by the inner portion of the target. As such, ultrasonic imaging apparatuses are relatively compact and inexpensive, capable of real-time display, and relatively safe as radiation exposure is not an issue.
Further, medical equipment has been developed that allows for the output of a three-dimensional (3D) image of the inner portion of the target. Moreover, methodology of creating a 3D panoramic image with respect to the inner portion of the target by synthesizing a plurality of 3D images has been developed to secure a larger observation region.

Method and apparatus to generate 3D volume-panorama image based on 3D volume images


A control device (10) includes: target deceleration calculation means (101) for calculating a target deceleration by using a target deceleration map in which a target deceleration is set for each vehicle speed; command power-generation torque calculation means (102) for calculating a command power-generation torque based on the target deceleration, a rotation speed of a power generator (2), and a transmission gear ratio of a transmission (3); and command Duty calculation means (103) for calculating a command Duty based on the command power-generation torque, and the rotation speed and an output voltage of the power generator (2). The target deceleration map is calculated based on a vehicle-speed shift in accordance with actual running conditions when a vehicle is decelerating with fuel stop.

In recent years, as a technology for reducing fuel consumption of a vehicle, there has been developed a vehicle which stops fuel injection and recovers kinetic energy of the vehicle as electric power by regenerative power generation in the case where there is no acceleration request by an operation of an accelerator pedal when the vehicle is decelerating. In such a vehicle, it is important to set a power-generation torque to an appropriate value so as to obtain a regenerative power-generation amount as large as possible while preventing deceleration feeling of the vehicle from being excessive at the time of regenerative power generation.
For example, in a related-art device disclosed in Patent Literature 1, it is described that a target deceleration (target negative acceleration) is set larger as a vehicle speed becomes higher. A power-generation amount of a power generator is controlled so that an actual deceleration (actual negative acceleration) becomes equal to the target deceleration. In this manner, maximum fuel efficiency improvement effects are intended to be achieved by recovery of deceleration energy by the regenerative power generation and setting of optimal fuel stop time.

Vehicle power-generator device and vehicle power-generation control method


A polysaccharide comprising galactose, glucose, rhamnose, and pyruvic acid as constituents, wherein the galactose, glucose, and rhamnose are contained in a molar ratio of 4:2:1, and the pyruvic acid is contained in an amount of 4 to 7 wt %. The polysaccharide can be obtained by culturing Bifidobacterium longum JBL05 (NITE BP-82) under anaerobic conditions.

Microorganisms belonging to the genus Bifidobacterium are one of the most dominant bacteria in the intestinal bacterial flora. The microorganisms themselves can be ingested, as in the case of lactic acid bacteria. It has been reported that ingestion of the microorganisms provides properties, for example, an action of regulating the functions of the intestines by conditioning a balance in the intestinal bacterial flora, an effect of improving the serum cholesterol level, and an immunostimulating action. There are reported agents for enhancing immune functions, among the above-described properties. Examples of the agent include an antitumor agent containing lactic acid bacteria or microorganisms belonging to the genus Bifidobacterium as an active component (Japanese Laid-Open Patent Publications No. 7-82158), an accelerator for production of cytokine (Japanese Laid-Open Patent Publications No. 8-92112), an agent for preventing and treating inflammatory bowel diseases containing microorganisms belonging to the genus Lactobacillus as an active component (Japanese Laid-Open Patent Publications No. 2003-73286), a granulocyte inducer containing cell walls and/or disrupted cell walls of microorganisms belonging to the genus Bifidobacterium as an active component (Japanese Laid-Open Patent Publications No. 7-330806), and a water-soluble immunostimulating substance containing microorganisms belonging to the genus Bifidobacterium as an active component (Japanese Laid-Open Patent Publications No. 9-241179). However, active components of all of these agents are bacteria themselves or polysaccharide fractions obtained by treatment with cell wall-digesting enzymes or ultrasonic disruption of bacteria.
On the other hand, regarding the immunostimulating action provided by an extracellular polysaccharide, it is reported as the follows: an antitumor agent containing a polysaccharide produced by Streptococcus lactis or Streptococcus cremoris as an active component (Japanese Patent No. 2678673), an antitumor activity of viscous capsular polysaccharides of Lactococcus lactis subsp. cremoris or Lactococcus lactis subsp. lactis (Japanese Laid-Open Patent Publications No. 1-277484), an anti-inflammatory agent or a bone marrow cell growth accelerator containing a polysaccharide obtained from a culture suspension of microorganisms belonging to the genus Lactobacillus as an active component (Japanese Laid-Open Patent Publications No. 7-70209), and a preventive effect of phosphorus-containing polysaccharides produced by Lactobacillus delbrueckii subsp. bulgaricus on autoimmune diseases (Japanese Patent No. 3017493). However, all of these reports relate to polysaccharides produced by lactic acid bacteria that have been separated from yoghurt or fermented milk.
Originally, the number of microorganisms belonging to the genus Bifidobacterium in the human intestinal bacterial flora is larger than that of lactic acid bacteria, and it seems that polysaccharides produced by the microorganisms belonging to the genus Bifidobacterium in the intestine have some biological defense functions. However, reported examples of polysaccharides produced by the microorganisms belonging to the genus Bifidobacterium are limited to polysaccharides containing only glucose produced by Bifidobacterium longum (Japanese Laid-Open Patent Publications No. 7-255465) and polysaccharides containing glucose, galactose, uronic acid, and other sugars produced by Bifidobacterium longum (Appl. Microbiol. Biotechnol. vol. 43, pp. 995 to 1000). Furthermore, their functions are not clear.

Polysaccharide produced by microorganism belonging to genus

Osaka Prefecture University Public Corporation


A level-shifting amplifier is provided for level-shifting an input signal with a voltage magnitude that exceeds a supply voltage of the amplifier. In operation, the amplifier has an input impedance of greater than 100M Ohms.

Level-shifting amplifiers include a class of amplifiers which shifts an input signal by a predetermined voltage. In some situations, it is desirable to handle an input signal with a range that extends beyond a supply voltage (i.e. rail) of a circuit. As set forth below, various circuits exist for such level-shifting purposes.
Prior art FIG. 1 illustrates an exemplary level-shifting amplifier circuit 100, in accordance with the prior art. Such circuit 100 includes an inverting operational amplifier LM324 with a non-inverting input coupled to ground. In use, the circuit 100 serves as a single-supply device powered by a positive rail with a return to ground. Since an input signal is inverted at an output signal of the circuit 100, the input signal may range from ground down to a negative voltage. Further, the output signal may swing from ground up to some (other) positive voltage determined by a ratio of feedback resistors R1, R2. Of course, the input impedance of the circuit 100 is the value of the input resistor R1.
Prior art FIG. 2 illustrates another exemplary level-shifting amplifier circuit 200, in accordance with the prior art. As shown, the instant circuit 200 dangles an emitter and base of a first pair of NPN bipolar transistors Q1, Q2 from a positive rail. Since all junction-isolated nodes are biased near the positive rail, an input signal may range as high as the positive rail minus a couple of volts down below a negative rail (ground) until a break down occurs. Depending on the design of the circuit 200, either the first transistor pair Q1, Q2 or a second transistor pair Q3, Q4 will break down first. The present circuit 200 is typically used in instrumentation amplifiers and high-speed digital line receivers. Further, the input signal being sensed generally must provide bias current for an input stage of the circuit 200.
Prior art FIG. 3 illustrates yet another exemplary level-shifting amplifier circuit 300, in accordance with the prior art. Such circuit 300 may traditionally be found in adjustable voltage regulators. As shown, a bandgap reference voltage Adj dangles below a substrate, which is connected to an output Vout of the circuit 300. A user-supplied resistor divider 302 is provided from the output Vout to a bottom of the reference to ground. The regulated output Vout is set as a function of a ratio of the resistors of the divider 302 times a value of the bandgap reference voltage Adj. Generally, an impedance of the resistive divider 302 is chosen to be fairly low, thus a current of the resistor divider 302 typically swamps a 10-20 uA current from a bottom of the bandgap reference voltage Adj.
Prior art FIGS. 4A and 4B illustrates still yet another exemplary level-shifting amplifier circuit 400, in accordance with the prior art. Such circuit 400 receives an input current i_ref 401 from a bias current generator. The current passes through an n-channel FET NE3 which serves as a power down disconnect. The current also passes through a conventional P-channel cascode current mirror formed by P-channel FETs pe3, pe5, pe6, pe1, pm7 and pm0. It may be noted that the FETs pe5 and pm0 have the same W/L parameters (i.e. width/length dimensions for FET gate, etc.), but the m-numbers (i.e. number of FETs connected in parallel, etc.) are in the ratio of 4:1. Consequently, the current in the output section of the current mirror (source-drain of pm0) is four times that of the input current i_refp.
Still referring to FIGS. 4A and 4B, current mirror output current (that is controlled primarily by FET pm0 and its cascode pm7) passes through a resistive load 421-424. In use, current passes through a source follower formed by a P-channel FET pf2 and an associated cascode device pif2. A voltage at node vout_p 460 is the sum of the input voltage vin_p (at node 470) plus offsets due to the resistive load 421-424 in addition to an offset due to the threshold of the source follower FET 451, and possibly other sources. As shown, gates of the FETs 451, 452 are tied together; this is operable because pif2 is a low threshold voltage type so that a constant 1.1V total appears across the source follower FET 451, thereby greatly increasing the linearity of the level-shifter across its full signal range.
With continued reference to FIGS. 4A and 4B, it should be appreciated that since a current through the resistive load 421-424 may need to generate a potential difference in the hundred(s) of millivolts, a bandwidth of the circuit 400 may become limited. Such an effect would be due to the time constant effect of the resistive load 421-424 working against the capacitance of the FETs 451, 452. In order to overcome excessive bandwidth limitation, an effectively high source impedance current source may formed by FET pair pe18 and pe19 to improve slew rate. This current source may be mirrored by a mirror circuit 485 from a supplied bias current ib using FETs pe30, pe22, pe23, pe24, pe25 working into FET pe18 and cascode FET pe19. It should also be appreciated that the action of the shifter in translating vin_p at node 470 to an offset vout_p at node 460 is for half (by convention the positive half) of a pair of differential signals. An entire duplicate shift arm of circuitry 490 exists for the negative signals vin_n to vout_n. That vin_p and vin_n are offset by a voltage which is set in both cases by current i_refp reflects the need for both signals to be offset by a near identical amount in order to avoid introducing error into the differential signal.
In use, the circuit 400 exhibits poor linearity with signals that exceed VTO beyond the rail. More information regarding such circuit 400 may be found with reference to U.S. Pat. No. 6,717,451.
Unfortunately, prior art amplifiers that level-shift a signal beyond a rail exhibit a low input impedance, or other characteristics that may potentially be undesirable. For example, some prior art amplifiers require a source to provide a significant bias current to power an input stage of the amplifier, etc. There is thus a need for overcoming these and/or other problems associated with the prior art.

High-impedance level-shifting amplifier capable of handling input signals with a voltage magnitude that exceeds a supply voltage


A roughened rubber bonding surface having a predetermined roughness of a rubber member and a roughened resin bonding surface having a predetermined roughness of a resin member made of a thermoplastic resin are connected to constitute a bonding interface, and ultrasonic vibrations are applied to the bonding interface from the rubber member side. Only the resin member is fused by friction heat generated in the bonding interface so as to force fused resin into the rubber member, and the fused resin that has been so forced into the rubber member is solidified therein, whereby both the rubber member and the resin member are mechanically bonded by virtue of an anchoring effect produced by the two members which are entangled together.

1. Field of the Invention
The present invention relates to a rubber/resin ultrasonic bonding method, and more particularly to a rubber/resin ultrasonic bonding method in which a bonding surface of a rubber member and a bonding surface of a resin member whose fusion point is lower than that of the rubber member are connected to constitute a bonding interface and the resin member is fused by friction heat generated by application of ultrasonic vibrations to the bonding interface from the rubber member side, so as to bond both the members.
2. Related Art
Conventionally, for example, when attaching a rubber member to a resin member, an affixing method using a pressure sensitive adhesive double coated tape and a resin pin crimping method in which a resin pin provided on a resin member is passed through a hole in a rubber member so as to be crimped at a distal end thereof have been in use.
In addition, a vulcanizing adhesion method is also known in which a bonding surface of a resin member is embossed when molding the resin member, so that a rubber member can be bonded to the bonding surface of the resin member so embossed when vulcanized (for example, refer to JP-A-5-99266).
On the other hand, although it is not a bonding method for bonding a rubber member and a resin member, an ultrasonic welding method is also known for welding a hard resin member and a soft member made of a thermoplastic elastomer of the same resin base as the hard resin member using ultrasonic vibrations (for example, refer to JP-A-2001-275751).
In this ultrasonic welding method, a bonding surface of a hard resin member made of polypropylene (PP) is connected to a bonding surface of a soft member made of a olefin based plastic elastomer having compatibility with PP and a Shore A hardness (JIS-A hardness) of 90 or greater so as to form a bonding interface, and both the members are fused by friction heat generated in the bonding interface by application of ultrasonic vibrations to the bonding interface from the oft member side, whereby both the members are fusion bonded by chemical bonding force generated by molecular bond.
The conventional methods have their respective problems as below.
Namely, in the affixing method using a pressure sensitive adhesive double coated tape, the production costs are increased by such an extent that the pressure sensitive adhesive double coated tape is used. In addition, since the adhesive double coated tape made of a different material remains on the bonding interface, there occurs a case to which this method cannot be applied.
In addition, in the resin pin crimping method, both the resin member and the rubber member need to be molded with high accuracy so that the thickness and position of the resin pin on the resin member can accurately match the diameter and position of the hole in the rubber member, this also leading to high costs.
Furthermore, in the rubber vulcanizing adhesion method, since the rubber member needs to be vulcanized for adhesion to the resin member while being vulcanized to be molded into a predetermined shape in such a state that the resin member, which has been molded into a predetermined shape in advance, is disposed at a predetermined position in a rubber vulcanizing and molding mold, a mold having a special and complex construction is necessary as the vulcanizing and molding mold, this also resulting in high mold fabricating costs.
On the other hand, in the ultrasonic welding method, this is really the method in which members of the same resin base which are compatible with each other are fused together so as to be fusion bonded by chemical bonding force, and a rubber member and a resin member cannot be bonded by this method.


The present invention relates to a pharmaceutical or dietary composition comprising deoxyuridine and a pharmaceutically or dietetically suitable carrier. Another aspect of the present invention relates to a method of supplementing the dietary needs of a subject. This method includes administering to the subject a dietary supplementing effective amount of deoxyuridine. Yet another aspect of the present invention relates to a method of treating cancer in a subject. This method includes selecting a subject having cancer and administering to the selected subject a therapeutically effective amount of uridine, thereby treating the cancer in the selected subject.

Folate-mediated one-carbon metabolism is a metabolic network of interdependent biosynthetic pathways required for the de novo biosynthesis of purines, thymidylate ("dTMP"), and the remethylation of homocysteine to methionine (FIG. 1) (Barry Shane, Folate Chemistry and Metabolism, in FOLATE IN HEALTH AND DISEASE 1-22 (Lynn B. Bailey ed., Marcel Dekker, Inc. 1995)). Methionine can be converted to S-adenosylmethionine ("AdoMet"), the major one-carbon donor for cellular methylation reactions including the methylation of DNA, RNA, phospholipids, proteins, and small molecules (Barry Shane, Folate Chemistry and Metabolism, in FOLATE IN HEALTH AND DISEASE 1-22 (Lynn B. Bailey ed., Marcel Dekker, Inc. 1995); Fox et al., "Folate-Mediated One-Carbon Metabolism," Vitam. Harm. 79:1-44 (2008)). Impairments in one-carbon metabolism due to nutrient deficiencies and/or single nucleotide polymorphisms diminish dTMP synthesis, leading to elevated deoxyuridylate ("dUTP") pools, increased rates of dUTP misincorporation into DNA, and consequently futile cycles of DNA excision repair and chromosomal strand breaks (James et al., "Diet-Induced DNA Damage and Altered Nucleotide Metabolism in Lymphocytes from Methyl-Donor-Deficient Rats," Carcinogenesis 10(7):1209-1214 (1989); Branda et al., "Folate Deficiency Increases Genetic Damage Caused by Alkylating Agents and Gamma-Irradiation in Chinese Hamster Ovary Cells," Cancer Res. 53(22):5401-5408 (1993); Duthie et al., "DNA Instability (Strand Breakage, Uracil Misincorporation, and Defective Repair) is Increased by Folic Acid Depletion in Human Lymphocytes in Vitro," Faseb. J. 12(14):1491-1497 (1998)).
Altered folate metabolism also influences chromatin methylation patterns, including genome-wide CpG hypomethylation and site-specific hypermethylation, and altered histone methylation, which modify gene expression patterns (Wainfan et al., "Methyl Groups in Carcinogenesis: Effects on DNA Methylation and Gene Expression," Cancer Res. 52(7 Suppl):2071s-2077s (1992); Friso et al., "A Common Mutation in the 5,10-Methylenetetrahydrofolate Reductase Gene Affects Genomic DNA Methylation Through an Interaction with Folate Status," Proc. Natl. Acad. Sci. U.S.A. 99(8):5606-5611 (2002); Gaudet et al., "Induction of Tumors in Mice by Genomic Hypomethylation," Science 300(5618):489-492 (2003)).
Therefore, the loss of DNA integrity due to increased genome instability and/or changes in gene expression due to altered genome methylation are candidate causal pathways for folate-mediated pathology. Population and clinical studies have established that impairment of folate-mediated one-carbon metabolism, due to nutritional deficiencies and/or variations in one-carbon metabolism genes increases risk for birth defects including neural tube defects ("NTDs"), chronic diseases including cardiovascular disease, and certain cancers. However, molecular mechanisms have not been established, and biomarkers that predict disease risk have not been established.
For instance, during embryogenesis, the neuroepithelium bends and fuses to form the embryonic neural tube through the process of neurulation. Failure of neurulation results in a spectrum of developmental anomalies collectively referred to as neural tube closure defects. Worldwide prevalence of human NTDs ranges from <1-30 per 10,000 births (INTERNATIONAL CLEARINGHOUSE FOR BIRTH DEFECTS MONITORING SYSTEMS, WORLD ATLAS OF BIRTH DEFECTS (World Health Organization, 2d ed. 2003)). One of the strongest environmental determinants of NTD risk is low maternal folate status (Kirke et al., "Maternal Plasma Folate and Vitamin B12 are Independent Risk Factors for Neural Tube Defects," Q. J. Med. 1993; 86:703-8 (1993)), which interacts with specific gene variants to confer NTD risk (Relton et al., "Low Erythrocyte Folate Status and Polymorphic Variation in Folate-Related Genes are Associated with Risk of Neural Tube Defect Pregnancy," Mol. Genet. Metab. 81:273-81 (2004); Christensen et al., "Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Methionine Synthase, Folate Levels in Red Blood Cells, and Risk of Neural Tube Defects," Am. J. Med. Genet. 84:151 7 (1999)).
Low maternal folate status is one of the strongest environmental determinants of neural tube defect risk (Kirke et al., "Maternal Plasma Folate and Vitamin B12 are Independent Risk Factors for Neural Tube Defects," Q. J. Med. 86(11):703-708 (1993)) and interacts with specific gene variants to confer NTD risk (Relton et al., "Low Erythrocyte Folate Status and Polymorphic Variation in Folate-Related Genes are Associated with Risk of Neural Tube Defect Pregnancy," Mol. Genet. Metab. 81(4):273-281 (2004); Christensen et al., "Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Methionine Synthase, Folate Levels in Red Blood Cells, and Risk of Neural Tube Defects," Am. J. Med. Genet. 84(2):151-157 (1999)). Periconceptional folic acid intake at a level of 400 μg per day is recommended to all women of childbearing age to reduce the occurrence of NTDs (CDC, "Recommendations for the Use of Folic Acid to Reduce the Number of Cases of Spina Bifida and Other Neural Tube Defects," MMWR Recomm. Rep. 41(1-7) (1992)). Furthermore, food folic acid fortification has been introduced in the US, Canada, and Chile (Honein et al., "Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects," JAMA 285(23):2981-2986 (2001)) and has significantly reduced rates of neural tube defects (Czeizel et al., "Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation," N. Engl. J. Med. 327(26):1832-1835 (1992); Medical Research Council "Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group," Lancet 338:131-7 (1991)). However, the folate-dependent metabolic pathway(s) that affect neural tube closure are unknown. It is estimated that only 70% of NTDs are responsive to dietary folic acid (Berry et al., "Prevention of Neural-Tube Defects with Folic Acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention," N. Engl. J. Med. 341(20):1485-1490 (1999)). Other risk factors for NTD affected pregnancies include environmental and food-based toxins (Bhatt, "Environmental Influence on Reproductive Health," Intl. J. Gynecology & Obstetrics 70(1):69-75 (2000); Hutz et al., "Environmental Toxicants and Effects on Female Reproductive Function," Trends Rep. Biol. 2:1-11 (2006)), and obesity (Leddy et al., "The Impact of Maternal Obesity on Maternal and Fetal Health," Rev. Obstetrics & Gynecology 1(4):170-178 (2008)) and maternal diabetes (Hendricks et al., "Effects of Hyperinsulinemia and Obesity on Risk of Neural Tube Defects Among Mexican Americans," Epidemiology 12(6):630-635 (2001)). It is not known what fraction of the 30% of NTDs that are not folic acid responsive result from impairments in folate-mediated one-carbon metabolism, including metabolic disruptions resulting from vitamin B12 deficiency. Although it has been appreciated that genetic variants interact with folate status to influence NTD risk (Wlodarczyk et al., "Spontaneous Neural Tube Defects in Splotch Mice Supplemented with Selected Micronutrients," Toxicol. Appl. Pharmacol. (2005)), the vast majority of the genetic risk has yet to be identified (Beaudin et al., "Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview," Birth Defects Res. A Clin. Mol. Teratol. 85(4):274-284 (2009)).
As noted above, the causal metabolic pathways underlying folic acid-responsive NTDs have not been established. Further, folic acid supplementation has been linked to cancer prevalence (Ebbing et al., "Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12," JAMA 302(19): 2119-2126 (2009)). Thus, there is a great need for understanding the mechanisms underlying occurrence and recurrence of folate-deficiency related birth defects, as well as alternatives to folic acid supplementation.
The interactions among nutrients and genetic factors also play an important role in the development of numerous cancers including colorectal cancer ("CRC"). A strong, inverse association of folate status and CRC has been demonstrated; individuals with lowest dietary folate intake show a 40% to 60% increase in CRC risk when compared with individuals with highest folate intake (Giovannucci et al., "Folate, Methionine, and Alcohol intake and Risk of Colorectal Adenoma," J. Natl. Cancer Inst. 85:875-84 (1993); Ma et al., "Methylenetetrahydrofolate Reductase Polymorphism, Dietary Interactions, and Risk of Colorectal Cancer," Cancer Res. 57:1098-102 (1997); Kim et al., "Folate Intake and the Risk of Colorectal Cancer in a Korean Population," Eur. J. Clin. Nutr. 63:1057-64 (2009)). Genetic variation that alters folate metabolism and utilization also influences cancer risk (Ma et al., "Methylenetetrahydrofolate Reductase Polymorphism, Dietary Interactions, and Risk of Colorectal Cancer," Cancer Res. 57:1098-102 (1997)). The mechanism by which folate metabolism alters CRC risk is not known, which has led to concerns regarding the potential impact of elevated dietary folate intake and folate fortification initiatives on CRC incidence (Cole et al., "Folic Acid for the Prevention of Colorectal Adenomas: A Randomized Clinical Trial," JAMA 297:2351-9 (2007); Logan et al., "Aspirin and Folic Acid for the Prevention of Recurrent Colorectal Adenomas," Gastroenterology 134:29-38 (2008)).
The present invention is directed to overcoming these and other deficiencies in the art.

Use of uridine and deoxyuridine to treat folate-responsive pathologies


Apparatus and method for monitoring a prostate in a human body in which a fluid flows and which is characterized by a change in the prostate with time in space for the purpose of diagnosing a prostate condition, particularly cancer. A preselected place in the prostate is monitored to collect data at two or more time points correlated to a prostate event. The data is indicative of a prostate parameter that varies with time as a function of at least two variables related to prostate wash-in and wash-out behavior. A calibration map is made on a calculated basis with each pixel or voxel representative of a color hue indicative of wash-out behavior and a color intensity indicative of wash-in behavior. When a satisfactory map is obtained, the collected data is processed on the basis of the map to obtain an image of the preselected place with each spatial unit thereof correlated with a color hue and a color intensity. Software and a data processing system are provided to develop the calibration map. The calibration map and image of the preselected place are also novel implementations.

Presently apparatuses are known for monitoring testing or measuring a system in which a fluid that is flowing or substances in the fluid will dissipate in part as it traverses the system or will require regeneration. For example, MRI machines are used today to create images with or without administration of a tracer-contrast agent. Customarily, the machine is controlled to take a series of images at discrete time intervals and the images are then dynamically analyzed to obtain an output result. For example, dynamic studies of contrast enhancement in breast tumors have demonstrated that the rate of change in signal intensity is an important parameter for the distinction of breast masses, leading to pharmacokinetic studies. However, it is known that as a result of tumor heterogeneity, there are significant local variations in the time evolution of contrast enhancement, and, therefore, maintaining high spatial resolution in both the recording and analysis steps is very important. In a standard clinical MRI of the breast, it is difficult to achieve high spatial resolution and also maintain high temporal resolution. In most dynamic studies performed previously, the emphasis was on high temporal resolution (at the expense of spatial resolution) monitoring the equilibration in the intravascular space and early diffusion into the extracellular space of the tissue. As a consequence, in standard MRI machines the output results are sometimes inconclusive.
Prostate cancer is the leading form of cancer diagnosed in males and the second leading cause of cancer-related death in men in the USA, as well as in many other Western countries. One out of every six men is at lifetime risk for prostate cancer. This high prevalence, and a rising age-adjusted mortality rate, makes prostate cancer a major socioeconomic problem. In 2001 alone, an estimated 198,000 men in the United States were diagnosed with prostate cancer and 31,500 succumbed to it.
In the past, prostate cancer was only diagnosed when symptoms of advanced disease appeared. Currently, the best way to detect prostate cancer is to measure the level of the serum prostate specific antigen (PSA) in a blood test and to use a digital rectal examination (DRE) to feel for lumps on the prostate. Additional important tests used to diagnose prostate cancer include: (i) urine test for blood or infection; (ii) transrectal ultrasonography using a probe inserted into the rectum, which creates a picture based on the detection of the echoes of sound waves; (iii) intravenous pilogram of a series of X-ray pictures of the organ and the urinary tract; (iv) cytoscopy inspection of the urethra and the bladder via a thin lighted tube; and (v) biopsy—removing tissue, usually with a hollow needle, for pathologic examination.
Prostate specific antigen (PSA) is an enzyme produced by the epithelial cells of the prostate. Small amounts normally leak into the circulation with reported concentrations of less than 4 ng/ml. However, normal PSA levels may vary with age, for example, from 2.4 ng/ml for men aged 41-50 years to 6.5 ng/ml for men aged 71-80 years. Routine PSA tests are extremely valuable for monitoring for prostate cancer recurrence. A fall in PSA values indicates a favorable response to primary treatment. PSA is not cancer specific, and certain disorders and interventions such as benign prostatic hyperplasia, prostatitis, prostatic infraction, prostate surgery, and a prostate biopsy also elevate the PSA level. The reported sensitivity of the PSA test is 43-81%, and its specificity is 59-93%. Since 25% of men with PSA levels between 4-10 ng/ml have malignant disease, a biopsy is usually recommended for these patients. Of the 15 million men tested in 1998, 15% or 2.25 million men had PSA levels considered higher than normal and thus faced the prospect of biopsy. Because the lesion is difficult to visualize on transrectal ultrasound (TRUS), male prostate biopsies are performed "blindly", without regard to what may be localized areas. Sampling becomes a key issue in such situations, and over the last years there has been a shift from limited sampling (2 cores on each side), to increase sampling (3 cores on each side or 6 cores on each side and separate sampling of the seminal vesicles). Even with 13 cores, however, it is still possible to completely miss areas of carcinoma, and hence, understage the disease.
The introduction of the FDA-approved PSA serum test in 1987 was followed by a dramatic increase in the findings of new prostate cancers in the USA. Previously, when cancers were largely being diagnosed based on symptoms alone, the detection rate with DRE was only 1%, and 30% of patients had a clinically localized, potentially curable disease. In the PSA screening tests of men without symptoms, detection rates are as high as 5%, and 70%-98% of the patients have a potentially curable disease. The improvement in biopsy techniques with respect to technology and method of sampling the prostate has resulted in an improved early detection of smaller tumors.
Staging and grading of prostate cancer are vital for the management of the disease. Staging is a careful attempt to find out whether the cancer has spread and, if so, what parts of the body are affected. The results of staging are useful for selecting the appropriate therapy for the patient. The stages are characterized as follows. In stage I, the cancer cannot be detected by a rectal examination and causes no symptoms. Stage I tumors may be in more than one area of the prostate, but with no evidence of spread outside the prostate. In stage II, the tumor is felt by DRE or detected by the PSA test, but there is no evidence of spread outside the prostate. In stage III, the cancer has spread to nearby tissues, and in stage IV, to the lymph nodes or to other parts of the body.
Grading determines the pathologic nature of the cancer with reference to normal prostate tissue, primarily in relation to the state of aggressiveness and growth capacity of the cancer. The Gleason system is the predominant system used in describing prostate carcinoma grade. It is based on the assessment of two properties: differentiation and likelihood for the prostate cancer to spread, i.e., the tumor metastatic capacity.
Prediction of disease stage from preoperative information is possible, especially in the extremes. Several models were developed based on preoperative features such as: (i) PSA serum level (a PSA value between 4 and 10 ng/ml detects organ confined disease in 75% of cases, but this proportion decreases to 48% if the PSA value is greater than 10 ng/ml; a PSA value greater than 40 ng/ml is generally indicative of metastatic disease); (ii) the prostate gland volume as measured by ultrasound; (iii) the tumor volume as measured by DRE; (iv) the tumor length and volume on core biopsy; (v) biopsy sampling methods; (vi) PSA density; (vii) microvessel density; and (viii) histologic grade, as measured by the Gleason method.
The three most used method for the diagnosis of prostate cancer are computed tomography (CT), TRUS and MRI. All these methods have been evaluated as tools for staging prostate cancer. Of the three, MRI appears to have the greatest potential utility in providing diagnostic information, i.e. detection, staging and biopsy guidance. CT has reported accuracies ranging from 47%-75% for local staging of prostate cancer. Even though at the higher accuracies CT could compete with TRUS, it is generally not used for local staging of prostate cancer. Even though the accuracy of TRUS in staging prostate disease has been reported to be as high as 86% and as low as 38%, most reports indicate the TRUS is not as valuable as MRI in local staging. The major role of TRUS is in guiding needle biopsies. In addition, TRUS has been the modality of choice in determining prostatic volumes, even though there is some reader variability reported for these volume measurements.
The soft tissue contrast of MRI and the ability of MRI to acquire multi-planar images have increased its ability to evaluate the internal pelvic structures. T1-weighted images maximize the contrast between fat and solid organs or viscera and have been used to evaluate lymphadenopathy. T2-weighted images characterize the internal structure of solid organs and provide a high contrast between tumor and normal muscular tissue. However, this distinction is often lost in the prostate and depends on the location of the pathologic changes within the prostate. Due to similarities between tumor and central gland tissues, poor discrimination results, particularly in the presence of coexisting benign disease. No significant improvement in the detection of extra-capsular extension was reported when fat-suppressed T2-weighted images were applied.
Pelvic MRI based on relaxation weighted imaging did not show a marked improvement in prostate cancer staging. As a result of this low accuracy, investigators have turned to use endorectal MRI coils in order to increase the sensitivity and specificity of MR imaging. The staging accuracy for endorectal coil MRI in preliminary studies varied between 68% and 82%. Staging of local disease was considerably poorer at 57%. The utility of endorectal imaging for prostate cancer has not been universally accepted. Yet, multivariable analysis has shown that endorectal MRI findings of extracapsular extension is the single most significant predictor of pathology at radical prostatectomy when compared with clinical staging, serum PSA level, or the Gleason score on biopsy. Most researchers believe that endorectal imaging may be especially useful for the determination of seminal vesicle involvement, though extra-capsular extension can often be detected as well.
The use of contrast-enhanced MRI to diagnose prostate diseases has so far been limited. Recently, the ability of dynamic contrast-enhanced MRI to differentiate benign from malignant prostatic disease has been evaluated (Liney G P, Turnbull L W and Knowles, 1999, In vivo magnetic resonance spectroscopy and dynamic contrast enhanced imaging of the prostate gland, NMR in Biomedicine, 12, pp. 39-44; Turnbull L W et al., 1999, JMRI 9, pp. 311-316). The first study included 20 patients, and the second 13 patients who were candidates for radical prostatectomy based on transrectal ultrasound findings and negative radioisotope bone scans. Maps at pixel resolution of the maximum enhancement factor value and of the time taken to reach maximum enhancement were calculated. Significant contrast-uptake was observed with faster enhancement in tumor regions than in benign prostatic hypertrophy (BPH) regions. Considerable discrimination between the different regions was obtained, emphasizing the potential of contrast enhanced MRI in staging prostate cancer patients. In both studies, high temporal resolution (11 sec.) and low spatial resolution (6-7 mm slice thickness) were applied. It was indicated that the low spatial resolution in these studies is a serious limiting factor, especially when dealing with heterogeneous lesions.
Accepted standard treatments for prostate cancer include careful observation, surgery (radical prostatectomy, transurethral resection of the prostate), radiotherapy and hormone therapy. Many men, mostly elderly, whose prostate cancer is progressing slowly and is detected at an early stage, may not need treatment and undergo careful observation. For these patients, the possible risk and side-effects of surgery and treatment may outweigh the possible benefits of treatment. The decision as to who will benefit from a prostatectomy is a major issue. Clearly, some of these men die before their prostate carcinoma causes significant problems and such tumors have been described as "insignificant." Others undergo a radical prostatectomy only to discover that their tumors have grown beyond the prostate, and 50% of these men will suffer a recurrence. Finally, there are patients who will most likely benefit from radical prostatectomy.
The staging and prognosis of patients at the lower and upper ends of the Gleason score spectrum are more readily predicted. However, most patients today are found initially with these parameters in an intermediate range. Additional information about disease extent is needed for early and accurate staging and treatment, as well as to determine a better means to follow patient progress.
Currently, however, there is no precise clinical method for the reliable assessment of local extent of prostate cancer. This is a major drawback in the treatment of localized disease.

Apparatus for monitoring a system with time in space and method for diagnosing a condition of a prostate