The present invention relates to a frequency domain near infrared absorption device for assessing tissue damage in a wound without physically contacting the wound.
A variety of instruments based on the diffuse propagation of Near Infrared (NIR) photons due to multiply scattered light have been used in the prior art to obtain clinically meaningful information about living tissue, such as tissue oxygenation. Such devices rely on optical fibers to transport the incident and scattered lights; however, the fiber optical probe is in contact with the tissue under examination. One of the key advantages of these laser technologies is their non-invasive nature; however, this advantage is negated by the fact that the fiber optical probe contacts the tissue under examination.
The present inventors have previously described in an article entitled “Optical Properties of Wounds: Diabetic Versus Healthy Tissue,” IEEE Transactions on Biomedical Engineering, Vol. 53(6), pages 1047-1055, June, 2006, such a frequency domain NIR instrument with one source position, four detector channels, three wavelength diode lasers (λ=685 nm, 785 nm and 830 nm) and a source modulation frequency of 70 MHz. Such a device has been demonstrated by the inventors as useful in assessing the early healing process of wounds in healthy and diabetic animals. For example, the device incorporates the ability to assess the extent of hydration at the wound site in addition to the detection of oxygenated, deoxygenated hemoglobin and amount of blood. The wound healing assessment is further enhanced with the added capability to vary sensor penetration depth by adjusting the probe design. As illustrated in
However, the device of
Leonardi et al. describe in US 2006/0155193 another method for using a near infrared spectroscopy device to assess burn injuries. Leonardi et al. purport to use broadband white light and measure the intensity of the reflected light using a CCD. However, this device cannot obtain absolute values of absorption scattering coefficients but instead obtains relative changes. Moreover, the probe also must penetrate into the burned skin, which is generally undesirable.
There are many medical applications where it would be preferable or necessary not to touch the injury or wound site. Since the principle of operation of an fNIR device is to register the light scattered from the tissue, contact is not a limiting factor for the success so long as the light may be captured and its origin in the tissue accurately tracked. The present invention is directed to such a non-contact device.
Those skilled in the art will appreciate that in the field of NIR devices, the non-contact Continuous Wave (CW) method has been used for rapid and accurate acquisition of large data sets of tissue optical properties to reconstruct 2D or 3D images, for example, in breast imaging to detect tumors. Depending on the desired tissue volume to be covered (usually around 1 liter) and the required resolution (typically 0.2-1.0 cm), a very large number of measurements (from 103 to 105) are needed. A CCD camera is the most common device for reconstruction and is coupled with high quality lenses to achieve coverage of a substantial volume of tissue instead of an experimental probe with fibers, thus allowing for continuous wave (CW) measurements.
A frequency domain NIR device with a remote probe has been implemented for image reconstruction work and is based on a CCD camera coupled to a gain-modulated image intensifier with Fast Fourier Transform. This device is described in an article by Godavarty et al. entitled “Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera,” Physics in Medicine and Biology, Vol. 48, pages 1701-1720 (2003), and in an article by Gurfinkel et al. entitled “Determination or optical properties in semi-infinite turbid media using imaging measurements of frequency-domain photon migration obtained with an intensified charge-coupled device,” J. of Biomedical Optics, Vol. 9, pages 1336-1346 (2004). However, this device is very expensive and must be used on an optical table with very stable temperature and humidity conditions. As such, it is not suitable for clinical use.
A non-contact device having the same sensitivity and improved robustness compared to devices that must contact the wound is desired for many reasons. For example, a non-contact device may be used to obtain data from practically any wound and burn and, by not touching the injured skin, the measurements do not cause any pain or contamination of the wound. Other benefits of a non-contact device include the ability to maintain a sterile environment within measurements without a need for intermediate steps for sterilization, the elimination of operator variability due to differing contact pressures, and the ability to obtain measurements faster by a single operator. A non-contact device also may be mounted on a hyperbaric oxygen chamber for monitoring the status of a wound during and after treatments.
Several different types of frequency domain near infrared (fNIR) devices are known in the art. Currently three major experimental methods are used in the NIR range to measure absorption and scattering coefficients μα and μ′s in multiply scattering tissues. The key difference among the various techniques lies in the source of incident light. The simplest and easiest method uses constant power lasers as, for example, in continuous wave (CW) devices. Since the power source for this method is constant, it is only possible to measure one parameter, the intensity of scattered light. Changes in this light intensity are measured as a function of source-detector separation ρ. In the case of CW devices, however, difficulties emerge when trying to separate absorption attenuation from scattering effects. CW methods give a composite “picture” of light intensity changes and cannot distinguish scattering from absorption. It is however possible to distinguish scattering from absorption phenomena using the following equation:
Equation (1) represents a solution of the diffusion equation for infinite homogeneous highly scattering media where Φ(r, t) is the photon fluence, ν is the speed of light in turbid medium, D=ν/3μ′s is the photon diffusion coefficient, μ′s=μs(1−g) is the reduced scattering coefficient, g=<cos θ> is the mean cosine of the photon scattering angle, and μs is the reciprocal of the scattering length. The complex diffuse wave wavenumber is a very important parameter=kr+kt. The square of the wave number k2=(−3μαμ′s+iωtμ′s) is an expression where both coefficients μα and μ′s. are represented in an almost symmetrical expression and contribute in a similar way on the measured photon fluence Φ(r,t).
Both time resolution spectroscopy and the frequency domain technique are able to determine μα and μ′s simultaneously. In the case of time resolved spectroscopy, a sequence of very short light pulses falls on the tissue under investigation and the broadening and shape of light impulses scattered from the tissue is analyzed. Although a wealth of information can be obtained, this method is complex and expensive and is difficult to implement in a routine clinical setting.
Time resolution spectroscopy (TRS) instruments also are able to obtain high quality information about the optical properties of the tissue from the broadening of very short light pulses after their propagation in tissue. Although rich in information obtained, this method is complex and expensive and difficult to implement in a routine clinical setting.
The frequency domain technique with single modulation radio frequency RF of the incident light and variable source-detector separations can be used to simultaneously assess μs′ and μα of tissue, with a simpler and more cost effective device. Frequency domain devices measure directly two parameters: a) the intensity I(r,t) of scattered light, as in the case of CW methods, and b) the value of the phase shift Δφ, a parameter not obtained in CW methods. The phase shift is a result of the light modulation in that there is a shift between the RF of modulated scattered light compared to the phase of the RF oscillator which is used for modulation. The phase shift Δφ occurs because of the diffusive aspects of light propagation in tissue representing multiple light scattering phenomena. For typical optical measurements where light enters the tissue through the skin and leaves the tissue at distance ρ from the entry point, the real path of light R in the tissue is R˜(10-20)*ρ by reason of the diffusion propagation of light. Fitting the experimental values of intensity and phase shift to the solution of the diffusion equation allows simultaneous determination of μs′ and μα in tissues. For these reasons, the inventors believe that the frequency domain technique will provide the most suitable non-contact device.
The invention provides a system for providing non-contact measurements of wounds using a frequency domain NIR device. In particular, a frequency domain technique with single modulation frequency and variable source-detector separations is used to calculate μs′ and μα from the surface of wounds and tissues in vivo. The in vitro calibration of the device and the semi-infinite medium approximation to the diffusion equation then may be employed to extract optical coefficients from amplitude and phase measurements. In turn, the progress of the healing of the wound may be determined from the values of these optical coefficients.
A frequency domain modification of an fNIR device calculates tissue optical properties (scattering coefficient μs′ and absorption μα) from the measured amplitude and phase of scattered light. The amplitude of the diode laser radiation is modulated at RF frequencies. Measured data shows that, in the NIR region, the change of the absorption coefficient μα reflects the variation in oxygenated and deoxygenated hemoglobin concentration because hemoglobin is the main absorption chromophore in the wavelength range 680-850 nm along with water and lipids.
A device for measuring the progress of healing of a wound over time in accordance with a first embodiment of the invention includes at least one diode laser source that provides respective input wavelengths into one of at least two source fibers, a first optical switch that sequentially switches wavelengths among the respective input wavelengths into the one source fiber, a second optical switch that changes the at least one source between the at least two source fibers, a probe that does not touch the wound during use, the probe including the at least two source fibers and first and second detectors spaced thereon, and a processing unit that provides at least four independent measurements for calculation of an absorption coefficient μα and a scattering coefficient μ′s, whereby the progress of the healing of the wound over time may be determined from changes in the absorption coefficient μα and the scattering coefficient μ′s.
In the first embodiment of a non-contact probe configuration, the probe receives beams of input wavelengths from the at least one diode laser source via at least one of the at least two source fibers. The probe comprises a cube beamsplitter and a relay lens that together focus the beams on the wound. The relay lens and the cube beamsplitter are preferably configured such that scattered light from the wound returns to the first and second detectors through the relay lens and the cube beamsplitter. A CCD camera may be positioned to image the incident light on the surface of the wound through the relay lens and cube beamsplitter.
In a second embodiment of a non-contact probe configuration, the at least one diode laser source provides respective input wavelengths into a single source fiber and a single optical switch sequentially switches wavelengths among the respective input wavelengths into the single source fiber. In this embodiment, the non-contact probe includes the source fiber and four detectors spaced thereon, where the probe receives beams of input wavelengths from the at least one diode laser source via the source fiber. As in the first embodiment, the probe comprises a cube beamsplitter and a relay lens that together focus the beams on the wound.
Applications of such a non-contact device includes assessment of wound healing, pressure sores, ischemia for various diseases and their complications. The device also may be used for chronic wound healing and burn treatment, to evaluate the efficiency of hyperbaric oxygen treatments, or to evaluate the effectiveness of wound and burn gels, scaffolds, and other treatment modalities.
A detailed description of illustrative embodiments of the present invention will now be described with reference to
The inventors have found that the method of Diffuse Near Infrared Spectroscopy (DNIS) allows the determination of the optical properties, specifically the absorption coefficient (μa) and scattering coefficient (μs′) of non homogeneous, strong light scattering media. Human and animal tissues can be analyzed quite accurately using the diffusion approximation of DNIS. Several non-invasive optical experimental techniques widely used for medical applications differ mainly by the type of incident light that illuminates the human or animal tissue. If frequency domain devices are considered where the incident light of NIR lasers is modulated by only one radio (RF) frequency, the absorption coefficient may be determined by measuring how the intensity of light scattering and the phase of registered light changes as a function of the distance between the light sources (mostly source fibers) and the detector fibers. The source and detector fibers are inserted in fixed positions on an experimental probe, usually made from a plastic semi-flexible material. A number of different combinations in source-detector distances is possible and gives rise to different device configurations, for example, 1 source—4 detectors, or 2 sources—2 detectors. In both of these cases, four experimental points are measured at four distinct source-detector separations. Typically, the probe is placed in full contact with the surface of tissue under investigation, which is illuminated through the source fibers. The required condition is that all fibers must be in contact with the tissue. The light registered by the detectors fibers consists of light that underwent multiple light scattering and as a result is propagating back to the surface; this corresponds to the semi infinite geometry of the diffusion approximation.
The typical experimental setup is shown in
However, as noted above, in several medical applications full contact between a probe and the surface of tissue is not a preferred mode of application, for example, in infectious wounds, in burns, or for measurements in during open surgery. The inventors have therefore developed a geometry for the Frequency Domain Device of DNIS where any contact between the fiber probe and the tissue is absent.
To design such a non-contact device, it is first desirable to accurately assess using non-contact optics the source/detector distance. In medical applications, the dependence of amplitude and phase on the source-detector separation ρ is fitted to theoretical formulas for calculating μs′ and μα. The accuracy of the determined optical properties depends on the precision of ρ. In traditional probes, the source/detector separation can be measured easily by different methods. In non-contact methods, on the other hand, the optical system transfers the image of skin to the plane of the detector fibers and also focuses the incident light on the skin surface. In order to overcome this problem, the detector fibers are placed in a special holder similar to the probe of
A non-contact device also needs a method for capturing true scattered light while minimizing artifacts such as stray beams. This is the case because the power of scattered light is very small and any stray beam can insert serious error into any results. Reflected beams from the skin surface can practically go in any direction because the surface of the skin is a rough surface and diffuse reflection with a range of reflection angles close to 180 degrees may be obtained.
In most clinical applications, the gap between the traditional probe and the skin is very small because the probe presses onto the skin with small pressure. Therefore, the light reflected from the spot of incident light cannot go back to the detector fibers. In order to minimize stray beams, the relay lens must be used as the main element of the optical system because lens construction limits and attenuates the stray beams stronger compared to usual lens systems.
Frequency Domain Device with Two Sources—Two Detectors
Current trends in creating new electronics and optoelectronics devices focus on the design and assembly of more compact yet highly reliable instruments as compared to ones available in the market several years ago. As particular optoelectronic elements become rather inexpensive and miniaturized, the cost effectiveness of such small devices is now attractive for mass deployment.
An exemplary embodiment of a 2×2 non-contact device in accordance with the invention is illustrated in
Necessary changes of the two source-two detector device versus the device of
The measured light amplitude and phase shift consist of both instrument and sample contributions. The amplitude obtained in each channel depends on the transmission of the optical fibers, the sensitivity of the avalanche photodiode, the gain of each detector block and the coupling of the fibers. The phase shift may be different in each channel because the optical and electrical signal delay depends on fiber length and coupling, length of RF coaxial cables, and delays in the detector circuits. Instrument calibration is designed to allow for separate variability due to the instrument hardware components from sample and measurement variability.
The probe 32 shown in
The non-contact theory derives an expression for the fluence Φ({right arrow over (r)}) as a function of effective distances rb and r1, which depend on the Fresnel reflection at the tissue-air interface, the transport mean free path l* and the source-detector separation ρ along the sample surface.
where k=kreal+ikimag is a complex diffuse wavenumber. For measurements on tissue surfaces, r1 and rb can be written as:
Here ρ is the distance between the source (at ρ=0) and the detector position. In the semi-infinite geometry, when the detector is not close to the isotropic point source ρ>3*l*, a simple linear relation can be written:
Aatt(ρ) is the experimental intensity of scattered light measured in mV (millivolts), Θlag(ρ) is the experimentally measured change of phase relative to the phase of the 70 MHz generator, and V is the velocity of light in the medium (tissue). The corrected (using the calibration coefficients) experimental values of amplitude and phase are fitted to equation (4) and allow calculation of kreal,kimag. The algebraic relations (5) allow the calculation of the absorption coefficient r1α and the scattering coefficient μ′s.
A detailed drawing of the optical parts of a first embodiment of a non-contact probe is shown in
Scattering from the tissue 5 returns to the detection system through the relay lens 50. The Field Of View (FOV) of the relay lens 50 determines the size of the area that can be registered by the non-contact probe. The cube beam splitter 52 allows the light to be sent to the detector fibers 37, 38 that are placed in the focal plane of the relay lens 50. Using a CCD camera 54, the position of the incident light on the surface of the tissue 5 to be imaged can be followed along with the location of the image registration by the detector fibers 37, 38. During system calibration, silicone phantoms are used to determine the exact positioning of the optical components. All detector fibers 37, 38 can be placed in a common holder like that of
Those skilled in the art will appreciate that this machine vision measurement system offers a versatile solution for the non contact probe device. All optical elements can be designed and assembled by movable mounting flanges in one compact and reliable integrated system.
As noted above, in a non-contact probe the power of scattered light is very small and any stray beam can insert serious error in the obtained results. The existence of stray light in a contact probe is checked by measuring phantoms and volunteers, with and without a thin layer of immersion gel between the probe and the sample (phantom or skin). The immersion gel provides a medium of matching refractive index to the skin and is expected to decrease the intensity of reflected light by 20-40 times. In experiments, the obtained values of μα and μ′s were identical, within experimental error±3-5% in the presence or absence of the immersion gel. This proves that the contact probe has minimal influence of stray beams because the intensity of reflected light depends strongly on Δn—the difference between the refraction indexes of both media at the boundary of incident light, Ireflec˜(Δn)2 (Fresnel formulas). The immersion gel has a refractive index very close to the refractive index of skin and optical fibers. In order to minimize stray beams, a relay lens as the main element of the optical system should be used because lens construction limits and attenuates the stray beams stronger compared to usual system of objectives and lens systems.
In the optical embodiment of
As illustrated in
In the non-contact embodiment of
Those skilled in the art also will readily appreciate that many additional modifications are possible in the exemplary embodiment without materially departing from the novel teachings and advantages of the invention. For example, the embodiments above contemplate 1 source—four detector and 2 source—2 non-contact detector configurations. Those skilled in the art that other configurations are certainly possible with appropriate adjustments in the optical system. Accordingly, any such modifications are intended to be included within the scope of this invention as defined by the following exemplary claims.
The present application claims priority to U.S. Provisional Patent Application No. 61/111,924, filed Nov. 6, 2008. The contents of that application are hereby incorporated by reference.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US09/63564 | 11/6/2009 | WO | 00 | 5/10/2011 |
Number | Date | Country | |
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61111924 | Nov 2008 | US |