Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1999-12-10
2003-12-09
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S407000, C600S410000, C600S436000, C600S437000, C600S473000, C600S476000, C424S009200, C424S009300, C424S009520, C424S009600
Reexamination Certificate
active
06662040
ABSTRACT:
The present invention relates to the use of contrast agents to achieve contrast enhancement in in vivo photoacoustic imaging of human or non-human animal subjects.
Energetic radiation incident on certain materials is absorbed. When absorption results in heat output, there is a local rise in temperature. The temperature returns to that of the surroundings after the irradiation ceases. If the incident radiation is a sharp pulse, heat propagates from the absorption site as a thermal wave, which may be converted into a pressure pulse on contact with a suitably expanding medium (for example, a gas at the surface of the sample). When the incident irradiation varies in intensity at a characteristic frequency, there is periodic heating and cooling at the absorbing site that translates to periodic heating and cooling at the surface accompanied by periodic pressure changes at the surface. These can be detected as sound that has a fundamental frequency equal to that of the intensity variation of the incident radiation.
Whether the thermal wave reaches the surface after a pulse of light is determined by the thermal diffusivity and thickness of the sample. The detection of. sound waves actually generated at the sample surface is therefore generally only suitable for very thin samples. However, if the absorbing site expands sufficiently following light absorption, sound can also be produced directly at the interface between the absorbing site and the surrounding medium. When the incident radiation is a sharp pulse, the pressure increase produced by expansion of the absorbing site is temporary, but nevertheless a pressure disturbance propagates at the speed of sound from the absorbing site following the pulse. This can be detected with a transducer at some distance from the absorbing site as a time-dependent change in pressure. The elapsed time between the initial irradiation and the arrival of the pressure disturbance at the detector provides an indication of the distance of the absorbing site from the transducer. The shape of the detected pressure disturbance provides information about the shape of the incident pulse and the shape of the absorbing site. The time-domain signal is equivalent to a distribution of sound waves of different frequencies in the frequency domain. The shape of the distribution and the phases of the individual frequencies in the distribution are determined by the length of the irradiating pulse, the shape of the absorbing site, its distance from the point of detection, and the sonic properties of the medium.
When the intensity of the incident radiation varies periodically with a characteristic frequency, there is a corresponding rise and fall in the pressure imposed on the surrounding medium by the absorbing site. The pressure changes radiate throughout the sample as sound with fundamental and harmonic frequencies equal to those of the incident radiation. Detection at the frequency at which the incident radiation varies permits direct determination of one point in the frequency domain. In principle, the entire distribution in the frequency. domain can be found by making measurements at many different frequencies.
The generation of sound waves by incident radiation is known as the “photoacoustic” or “optoacoustic” effect and is reviewed by Tam (Reviews of Modern Physics, 1986, 58(2), p381-431). We use the two words interchangeably to refer to this phenomenon.
The incident radiation may be any type of energetic radiation, including electromagnetic radiation from radiofrequency to X-ray, electrons, protons, ions, and other particles. For simplicity, all of the above will be referred to herein as “radiation”. The word “light” will be used specifically to denote electromagnetic radiation of any wavelength or frequency.
Photoacoustic spectroscopy has been used as a sensitive means of detecting trace impurities in gases, and has developed into a useful analytical tool for the sensitive detection of chemical species in liquids and solids, within powders, or in highly turbid liquids, where severe light scattering would interfere with direct methods of spectroscopy (for example, see Rosencwaig, 1975, Anal. Chem., 47(6), p592A-604A; Karabutov et al., 1995, SPIE, 2389, p209-216).
Photoacoustic methods can be used for the determination of both the optical and physical properties of materials. The efficiency with which radiation is converted into heat and pressure within the material depends on its optical properties. The propagation of thermal, pressure or sound waves depends on the mechanical and physical properties. Thus, the photoacoustic signals carry information about the elasticity, density, thickness of component regions, thermal conductivity and specific heat, as well as the optical properties of the material in which they are generated. They can also provide data about the crystallinity of solid and semi-solid samples and can be used to detect phase transitions and discontinuities. When the light beam is focused, some of these properties can be measured locally. Localization of properties in a lateral plane, across a sample, is the basis of photoacoustic microscopy.
Photoacoustic depth profiling can be performed when the measured sound wave is analysed in terms of transit time from the site of light absorption back to the detector. Signals from deep within a sample take longer to reach the detector than those from regions near the surface. For pulsed irradiation the longer transit time translates into a larger separation between the time of arrival of the pulse and the arrival of the signal at the detector. For amplitude-modulated irradiation, the longer transit time translates into a phase change in the detected sound wave. Together photoacoustic microscopy and photoacoustic depth profiling constitute photoacoustic imaging.
The use of short bursts of light (chopped light) rather than continuously applied light is especially helpful for photoacoustic depth profiling. In this case, the absorption of each light pulse and subsequent heating of the various regions of the sample produces one or more positive or negative pressure waves that propagate radially from the site of absorption after each pulse. For very short light pulses, the shape of the pressure pulses generated by the light pulses is determined by the optical and thermal properties, sizes and shapes of the different regions of the sample, as well as by the speed of sound within the sites and the surrounding medium (see for example, Karabutov et al., 1996, Appl. Phys., 63, p545-563; Hutchins, 1986, Can. J. Phys., 64, p1247-1264).
For example, in an absorbing sample measuring 5 mm, the stress (pressure wave) signal persists at the detector for several microseconds. Mathematically, a single sharp pulse that is several microseconds broad in time can be decomposed through Fourier transformation into a continuous distribution of multiple sine waves ranging in frequency from 0 to megahertz. Even though sound in the form of a sinusoidal time dependent pressure wave is absent, detection of the pressure pulses still requires ultrasound transducers. The term “photoacoustic” and its synonym “optoacoustic” are still appropriate because the detected signals are a composite of normal sound waves.
Photoacoustic spectroscopy has also been applied to clinical and biological analysis. For example, cancerous cells have been detected in urine (Huang et al., 1990, J. Biomed. Eng., 12, p425-428). Depth profiling has also been performed. For example, studies have been made of the retina (Boucher et al., 1986, Applied Optics, 25(4), p515-520), skin (Giese et al., 1986, Can. J. Phys., 64, p1139-1141), the cockscomb of a rooster (Oraevsky et al., 1995, SPIE,-2389, p198-208), leaves (Nery et al., 1987, Analyst, 112, p1487-1490; Kirkbright et al., 1984, Analyst, 109, p1443-1447), lichen (O'Hara et al., 1983, Photochemistry & Photobiology, 38(6), p709-715) and on tissue equivalents (Kruger & Liu, 1994, Am. Assoc. Phys. Med., 21(7), p1179-1184; Esanaliev et al., 1996, SPIE, 2676, p84-90; Oraevsky et al., 1996, SPIE, 2676, p22-31). In eac
Coffey Steven Blair
Eriksen Marten
Gunther Wolfgang Hans Heinrich
Henrichs Paul Mark
Hollister Kenneth Robert
Amersham Health AS
Bacon & Thomas
Lateef Marvin M.
Lin Jeoyuh
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