Optical imaging using time gated scattered light

Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation

Reexamination Certificate

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Details

C250S358100, C250S458100

Reexamination Certificate

active

06321111

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates to medical and diagnostic imaging systems and procedures. Clinical procedures currently employ a number of systems for locating, imaging and diagnosing various structures within the human body. These include x-ray computer tomography, ultrasound, and magnetic resonance imaging, among others. These systems are used to detect morphologic abnormalities associated with specific diseases or conditions in various body organs.
In the case of x-ray computer tomography, for example, a number of projection data are taken sequentially at different angles and the data are used to reconstruct an image of the object being scanned in three dimensions. Thus, an x-ray tomography system solves an inverse problem for the x-ray opacity of body tissues using measurements of the amount of radiation absorbed from many beams transmitted at a variety of angles. This procedure is based on a number of assumptions including that the intensity of the x-rays diminishes across the distance traversed at a rate proportional to the intensity of the beam, that the absorption coefficient depends on the type of tissue along the various beam paths and that this non-linear problem can be solved based upon certain approximations including that a linear set of equations is an accurate representation of the problem. Of critical importance to x-ray tomography is that corrections for scattering are relatively simple.
Others have sought to use the “diffusion approximation” to represent the scattering of optical radiation for medical imaging applications. The diffusion approximation involves the detection of incoherent photons and the analysis of the resulting spectrum. The main problem with this approach is poor spatial resolution which limits the usefulness of this method in medical imaging applications. Others have sought to use so-called “ballistic” photons which travel the shortest path through the medium and are, for the purposes of this application, “non-scattered” photons.
A continuing need exists, however, for further improvements in the field of tomographic imaging for medical applications including enhanced resolution, reduced cost and complexity, and improved diagnostic capability.
SUMMARY OF THE INVENTION
The present invention relates to the use of time resolved elastic and inelastically scattered light for locating, imaging and diagnosing structures within organs of the human body. In particular time-resolved photon migration is used for medical imaging, including optical methods for localizing lesions within the body. Since biological tissue is highly scattering, the problem is one of imaging an object embedded in a turbid medium. Most existing techniques use differences in the absorption or elastic scattering properties between the embedded object and its surroundings. In many cases of medical interest, however, the resulting contrast is relatively small, which severely limits the sensitivity and resolution.
Fluorescence spectroscopy studies of human tissue indicate that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. Thus, intrinsic tissue fluorescence can provide enhanced contrast, as well as diagnostic-histochemical information. In addition, exogenous dyes, many of which are known to fluoresce with high quantum yield, have been shown to exhibit selective uptake in neoplastic lesions. Use of such agents provides fluorescent markers with high quantum yields, and are used to locate embedded lesions in the breast, brain and other organs.
In a preferred embodiment of the present invention time-resolved optical tomography, and fluorescence and Raman spectroscopy, can be used separately or in combination to provide both spatial and chemical information about embedded objects in tissue. By measuring and analyzing the early portion of the fluorescence signal from embedded lesions for example, which rises rapidly and is not sensitive to fluorescence lifetime, precise timing information and hence accurate spatial resolution of embedded lesions can be obtained. The rising edge of the fluorescence signal is generally over a period of 100-200 picoseconds or less. The rising edge of the Raman signal is less than 100 picoseconds. A streak camera can be used as a multichannel time-resolved detector to measure both the rising and decaying periods of the spectrum and to obtain images of embedded fluorescent objects in a single measurement or in a sequence of measurements at one or more angles relative to the tissue.
More specifically, a preferred embodiment collects scattered radiation in the interval between 0 and 1500 picoseconds, and preferably in the range of 0 to 500 picoseconds after irradiation of the tissue, and based upon a comparison of this data with a non-diffusion representation of light which has been scattered by the tissue. This non-diffusion representation emphasizes the “almost straight” trajectories of early arriving photons to provide images of internal bodily structures with improved spatial resolution in the range of 1-3 mm or less. This representation can include a diffusion component for later arriving photons in each collection period which exhibit characteristics more accurately represented by both diffusion and non-diffusion characteristics.
Time resolved Raman scattering of tissue involves the detection of early arriving photons arising from molecular vibration in the objects being measured. The vibrational bands can be assigned to individual molecular groups so that information about molecular content as well as position can be provided.
Optical collectors positioned about the object to be imaged are used to collect fluorescence and/or Raman light scattered by the tissue in response to laser irradiation. The fluorescence and Raman data can be used to locate and image embedded lesions in three dimensions as well as provide information regarding the chemical composition of such lesions. This information can be used to identify such lesions as normal or abnormal, cancerous or precancerous etc. Further details regarding the use of induced fluorescence of tissue to diagnose cancer or precancerous lesions can be found in U.S. Ser. No. 08/219,240 filed on Mar. 29, 1994, now U.S. Pat. No. 5,421,337, the entire contents of which is incorporated herein by reference. The use of laser induced Raman spectroscopy of tissue for diagnosing various diseases and conditions is described in greater detail in U.S. Ser. No. 08/107,854 filed on Aug. 26, 1993 and having an international filing date of Jan. 17, 1992, and entitled Systems and Methods of Molecular Spectroscopy To Provide For The Diagnosis of Tissue, the entire contents of which is incorporated herein by reference.
Another preferred embodiment utilizes back-scattered fluorescent and/or Raman data to provide measurements of depth and lateral position of lesions in tissue. Fiber optic probes used for back scattering measurements are described in conjunction with the above referenced incorporated applications. The time resolved methods can be used or, alternatively, frequency domain analysis of the acquired spectrum can also be employed. In this embodiment, it is desirable to modulate the laser above 100 MHZ, and preferably between 500 MHZ and 1000 MHZ to provide the temporal resolution for accurately imaging embedded objects. A computer is programmed to transform the data using known transformation techniques and the data can be represented in three dimensions with amplitude plotted as a function of frequency and time.
A preferred method of using the invention to diagnose tissue involves the insertion of a fiber optic probe into a body lumen, collecting data, determining the location of material to be biopsied, and performing a biopsy on the identified material. Additionally, biopsied samples can also be measured and analyzed using the methods described herein. Alternatively, an optical biopsy can be performed in vivo without the need for tissue removal using the methods set forth herein.
The above and other features of the invention including various nov

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