Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1999-12-10
2002-07-23
Smith, Ruth S. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S407000, C600S437000, C600S473000, C424S009600, C424S009510, C424S009610
Reexamination Certificate
active
06424857
ABSTRACT:
This invention relates to a method of diagnostic imaging of a human or animal subject, in particular a method in which the image is generated from detected light generated by or characteristically affected by ultrasound irradiation of the subject.
Optical imaging, also called light imaging, is perhaps one of the oldest of medical tools for screening and diagnosis. However, even now, optical imaging is largely limited to body surfaces. The primary advances in optical imaging have served essentially only to expand the range of body surfaces accessible to optical imaging techniques. Thus for example endoscopic techniques have made it possible to image from within the gastrointestinal tract, the cardiovascular system, the bladder, the vagina and uterus as well as the external surface of almost any internal organ. However, the deep interior of most organs, several centimeters beneath the surface, remains almost inaccessible to optical imaging.
There are two primary difficulties associated with subsurface optical imaging. These arise from light absorption and light scattering.
Naturally occurring substances in the body strongly absorb most visible light before it has travelled through typical tissue to any significant extent. Thus by way of example the absorption coefficient for light of 515 nm wavelength by human liver is 18.9 cm
−1
which means that on average a photon at 515 nm travels only about 0.5 mm in the liver before it is absorbed.
Because the photon follows a non-linear path within the tissue as a result of scattering, the actual depth of penetration before absorption is less than the pathlength of 0.5 mm.
Fortunately there is a wavelength “window” at 600 to 1300 nm in the red to near infrared region in which light absorption by the body is relatively weak. Thus for liver and breast tissue the absorption coefficients for light of wavelength 635 nm are only 2.3 cm
−1
and 0.2 cm
−1
giving mean pathlengths before absorption for photons at 635 nm of about 4.3 mm and 50 mm respectively. At these wavelengths, bone and brain are also relatively transparent so that absorption alone is not a barrier to light imaging with red to near infrared light. Thus, the penetration depth of light at 635 nm is an order of magnitude greater than that of light at 515 nm.
Light scattering however remains a major obstacle to light imaging of subsurface structures. Thus while light of wavelengths 600 to 1300 nm may pass through tissues and organs, the scattering that occurs means that the information on subsurface structures that would be extractable from the detected transmitted or reflected light is largely lost and small or deeply buried structures are not detectable distinctly by eye. At 635 nm, the scattering coefficient for human breast tissue is 395 cm
−1
meaning that while on average a photon will travel several centimeters before being absorbed it is constantly diverted by scattering events which occur on average every 2 &mgr;m. In other tissues, the scattering may be less severe but it is still substantial. The typical photon will travel only 16 &mgr;m between scattering events in brain grey matter for example.
While light scattering in the body is random, it is also highly anisotropic—the paths of the photon before and after a scattering event are not on average highly divergent. This scattering type is typical of Mie scattering.
To take account of the anisotropy of scattering, the reduced scattering coefficient &mgr;
s
′ is used in place of the simple scattering coefficient &mgr;
s
in certain mathematical models. &mgr;
s
′ is related to &mgr;
s
by the equation &mgr;
s
′=&mgr;
s
(1−g) where g is the average cosine of the angle between the photon's incoming and departing paths for scattering events. For human grey matter &mgr;
s
′ is only 7.22 cm
−1
meaning that light travels about 0.1 mm before its direction of propagation is significantly altered. This means that even after passing through several centimeters of breast or other tissue a light beam may still have a significant component which is travelling in substantially the same direction as the incident light beam. This component is often referred to as the quasi-ballistic component and it is this component which is of particular utility in light imaging of subsurface structures.
Thus, since the flight path of the quasi-ballistic photons through tissue is shorter than the path of the more highly scattered photons, the diffuse component, it is possible to separate out the transmitted light into its quasi-ballistic and diffuse components. This may be done for example by using a pulsed light source and detecting the leading edges of the transmitted pulsed light.
Despite its technical difficulties, light imaging has important advantages over other medical imaging modalities in that it can provide functional information as well as spatial information about the body. Thus with suitable modification it may be used for example to measure pH, oxygen content, metal concentration, etc.
Acousto-optical imaging is a modified approach to light imaging in which focused ultrasound is used to isolate optical signals from the body. Several mechanisms of interaction are possible. In one of these the acoustic wave sets up moving regions of different pressure, density and refractive index that interact with the light in much the same way as a diffusion grating. The movement of the sound waves moreover induces a Doppler shift of the sound frequency into the light frequency making it possible to identify that portion of the light that has actually interacted with the sound wave. Thus the light that has passed through the focused ultrasound region may be separated from other components of the detected light because it is shifted in frequency and wavelength. Acousto-optic imaging is described for example in U.S. Pat. No. 5,171,298, and by Wang et al.
Optics Letters
20: 629-631 (1995), Wang et al.
Proc. Opt. Soc. Amer.
ATuB3-1: 166-168 (1996), and Brooksby et al.
Proc. Soc. Photo
-
Opt. Instr. Engin.
2389: 564-570 (1995).
Acousto-optic imaging actually expands the ability of light imaging to provide functional imaging since the degree to which the focused sound waves interact with the light will depend upon the mechanical properties of the body at the focus site. The ability to measure tensile modulus and other mechanical properties of a suspicious lesion greatly facilitates identification of the lesion as malignant or benign.
Thus, in acousto-optic imaging the detected light signal carries a record of the interaction of ultrasound on the test object. Other phenomena also have this characteristic. In the phenomenon known as sonoluminescence, light is generated by the action of ultrasound on certain materials (see Suslick, “Ultrasound, its chemical, physical and biological effects”, VCH, New York 1988). Modulation of the frequency or amplitude of the ultrasound may impart a modulation to the sonoluminescence, and detection at the modulation frequency provides a means of separating out from the background the signal due to the ultrasound irradiation.
The present invention is directed at improvements in light imaging procedures where the detected light signal is affected by ultrasound irradiation of the human or animal body under study and in particular to the use of contrast agents in such imaging procedures. These contrast agents are materials which scatter, emit or absorb (or do two or more of these) light in the 300 to 1300 nm wavelength range, preferably the 600 to 1300 nm wavelength range, whereby the detected light signal is affected or generated by the ultrasound irradiation of the body, by the presence in (or absence from) the ultrasound irradiated portion of the body of the contrast agent and optionally by the selective sensitivity of the contrast agent to differences in its microenvironment within the body.
Thus viewed from one aspect the invention provides a method of generating information from (e.g. an image of) an animate human or non-human (e.g. mammalian; avian
Henrichs Paul Mark
Wolfe Henry Raphael
Amersham Health AS
Bacon & Thomas
Smith Ruth S.
LandOfFree
Use of acousto-optical and sonoluminescene contrast agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of acousto-optical and sonoluminescene contrast agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of acousto-optical and sonoluminescene contrast agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2918811