Photon Measurement Method and Apparatus
A system and method for measuring photons utilizing a low-power light source modulated with a code sequence to interrogate a sample of interest. Preferably a portion of the scattered light from the sample is detected by a photo-detector. A correlation of the photo-detector signal and the code sequence produces an estimate of the distribution of flight times for photons traveling from the source to the detector.
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This application is a continuation application claiming priority from the co-pending U.S. non-provisional patent application Ser. No. 11/381,450, entitled “Photon Measurement Method and Apparatus,” with filing date May 3, 2006, which is hereby incorporated by reference in its entirety.FIELD OF THE INVENTION
The field of the present invention pertains generally to systems and methods for detecting and measuring photons, including, more specifically, the measurement of the time-of-flight of photons traveling through a scattering media such as tissue.BACKGROUND
Diffuse optical imaging techniques are known in medical and biological applications. Overviews of diffuse optical imaging techniques can be found in “Recent Advances in Diffusion Optical Imaging” by Gibson, et al, Phys. Med. Biology, vol. 50 (2005), R1-R43 and in “Near-infrared Diffuse Optical Tomography,” by Hielscher, et al, Disease Markers, Vol. 18 (2002), 313-337. Briefly, diffuse optical imaging involves the use of near-infrared light incident upon a sample of interest. An example in the medical and biological field is optical mammography where near infrared light is used to illuminate breast tissue. A detector is placed on the opposite side of the breast from the incident light some distance away and collects scattered light from the breast tissue. The scattered light of interest that is detected may be directly scattered incident light or scattered fluorescence light caused by the excitation of an injected fluorescing material that fluoresces when exposed to the incident light. By measuring the amplitude of the light of interest at the detector and the distribution of photon arrival times at the detector for various source and detector positions, a reconstruction of the underlying tissue optical properties can be made. An overview of image reconstruction techniques can be found in the citations given in the aforementioned review articles.
Measurements of the photon flight-time distributions are typically carried out using either the time-domain or the frequency-domain technique. In the time-domain technique, the sample is excited with a pulse of light from a pulsed laser and the scattered light is measured using a detector with single-photon sensitivity. The detector measures the time delay between the excitation pulse and the first detected photon. The flight-time distribution is determined by using many repeated pulses and building up a histogram of the measured time delays. Unfortunately, the pulsed laser sources and single-photon detectors are relatively expensive. Because detection is typically done at the single-photon level, it can require a significant amount of time to build-up enough data to approximate the flight-time distribution. One disadvantage of the frequency-domain approach is that it is not a direct measurement of the photon flight time. Rather, it provides an estimate of the mean flight time based on the phase shift between a detected signal and the excitation signal. In some cases, more accurate image reconstructions can be obtained using more complete measurements of the flight-time distributions. This data is not readily obtained with frequency-domain instrumentation. A further disadvantage of the frequency-domain approach is the need for accurate high-frequency analog electronics. An overview of both the time-domain and frequency-domain techniques can be found in the above-referenced article by Hielscher, et al.
U.S. Pat. No. 5,565,982 discloses a time-resolved spectroscopy system using digital processing techniques and two low power, continuous wave light sources. The disclosed system requires two light transmitters of different wavelengths modulated with separate codes for interrogating a sample of interest. Properties of the sample are inferred by differential comparison of the return signals from each of the two light sources. It is undesirable to have two distinct light sources due to the cost and complexity involved. Furthermore, the noise level associated with a measurement made with two separate light sources will be higher than with a single source even if the codes used to drive the two sources are orthogonal.
A system and method capable of addressing these disadvantages while providing acceptable temporal information for whatever application the photon measurement is being used is needed.SUMMARY OF THE INVENTIONS
The inventions presented herein provide for direct measurements of photon flight-time using any single light source modulated with a known digital pattern. A preferred system uses information from a single low-power continuous-wave light source detected by a low-cost detector. Preferably the measurement system is implemented with digital electronics. One embodiment of the system and methods disclosed comprises an information from a single continuous-wave light source modulated with a digital waveform for interrogating a sample, a photo-sensitive detector for measuring the scattered light from the sample, and electronics for sampling the detector output and performing a correlation of the output signal with the modulation waveform. Other embodiments include electronics and software for determining the parameters of the flight-time distribution from the measured correlation.
A functional block diagram of a preferred photon measurement system 100 is depicted in
In the preferred photon measurement system 100, the detection optics 6 preferably include a second 3 mm diameter fiber bundle located between the optical filter and the optical detector 7. The optical detector 7 converts the scattered optical waves 21 to an electronic signal. In the preferred photon measurement system 100, the optical detector 7 is preferably a photomultiplier tube, model R7400U-20 from Hamamatsu Corp. In other embodiments, the optical detector 7 may be a PIN photodiode, an avalanche photodiode, a charge-couple device, or other suitable photosensitive element. As previously stated, the optical detector 7 preferably converts detected scattered optical waves 21 into an electronic signal which is communicated to the detected signal conditioner 8. The detected signal conditioner 8 preferably formats the signal so it may be converted to discrete samples by an Analog to Digital (A/D) converter 9. The A/D converter 9 outputs a detected response signal 19. The detected response signal 19 is communicated to a signal detector 10, where it is preferably correlated with the electronic reference signal 17 to extract a sample transfer characteristic.
Information about the temporal properties of the photons is preferably calculated from the sample transfer characteristic. This information preferably includes such properties as direct measurements of photon time-of-flight and the fluorescence lifetime. The estimate of photon times-of-flight is then preferably used to estimate characteristics of the tissue such as the absorption coefficient, scattering coefficient, or location of fluorescing material.
Another embodiment of the photon measurement system 100 includes an optical reference generator 22. The optical reference generator 22 preferably includes an optical splitter 12A or 12B that routes a portion of the modulated optical wave 20 to a secondary optical detector 13. The position of the optical splitter 12A or 12B can be either before or after the light delivery optics. The output of the secondary optical detector 13 is preferably routed to a secondary signal conditioner 14 whose output is communicated to a secondary A/D converter 15. The secondary A/D converter 15 preferably outputs a source reference signal 18 which can be correlated with the detected response 19 to extract the sample transfer characteristic. Using the source reference signal 18 as opposed to the electronic reference signal 17 allows the filtering of the temporal properties of the signal conditioner 2 and the modulated optical source 3 from the measured transfer characteristic.
The preferred hardware implementation of the A/D converter module and its interfaces to the signal detector 10 are shown in
The acquisition synchronizer 92 is preferably synchronized with an externally provided synchronization clock (SClk) 40 which is also preferably used to synchronize the signal generator 1. The signals CClk[1 . . . N] are preferably generated within the acquisition synchronizer 92 and preferably have the same frequency as SClk 40 but are offset in phase from SClk 40 in N fixed increments of (360/N)°, with the phase of CClk set to the fixed offset of Z°. In the preferred system the internal clock generation capabilities of the Xilinx FPGA are used to implement the acquisition synchronizer 92 directly. The A/D converters 90 preferably perform their conversions in sync with the conversion clocks 96 such that they generate samples at N discrete sample times spread evenly throughout the fundamental sample interval defined by the period of SClk 40. The effective sample rate for the array of converters is preferably N times the rate defined by SClk 40. This process of using multiple A/D converters sampling out of phase to increase the effective sample rate is what we call parallel over-sampling. In the preferred photon measuring system, parallel over-sampling results in an effective sample rate of 2 Gsamples/sec. The offset value Z allows the entire sample set to be offset by some phase from the synchronization clock 40. The acquisition synchronizer 92 preferably is configured such that the value of Z can be varied synchronously with the modulation frame, or with a block of frames called a frame block. This allows Z to follow a sequence of K values smaller than (360/N)° such that on successive modulation frames/frame blocks the effective sampling phases (relative to the synchronization clock) take on K values intermediate to those created by the N conversion clocks in any given frame. In this case preferably the input signal at any given A/D converter 90 will be sampled at K discrete phases over K blocks. The detected response 19 is preferably assumed to be stationary with respect to the start of the code pattern block over that time interval. The preferred K discrete sampling phases correspond to K discrete sample times and the effective temporal resolution of the sampling process is preferably increased by a factor of K. This process is referred to as temporal over-sampling.
In the preferred photon measuring system the value of Z is always zero and temporal over-sampling is achieved by adjusting the phase of the modulation as described below rather than by adjusting the phase of the A/D converter sampling. Preferably the FIFOs latch input data to the A/D converters 90 synchronously with the corresponding conversion clock 96. The FIFO 91 output data is preferably provided to the internal components of the signal detector 10 synchronously with the synchronization clock 40 such that all further processing is synchronized with the synchronization clock 40.
The preferred implementation of the Temporal Response Analysis Engine 11 are shown in
The functional blocks of the preferred signal generator 1 are shown in
The modulation signal 16 for both the LFSR 30 or pattern memory implementation is preferably buffered by an output buffer 35 to make the signals 16 more robust when driving external components. Timing for presentation of the code pattern bits is preferably controlled by a generation synchronizer 34 which preferably generates the master clock (MClk) 38 for the LFSR 30 and the address sequencer 33. The master clock 38 is preferably synchronized to a system synchronization clock (SClk) 40 which preferably controls both code pattern generation and response signal acquisition. MClk 38 preferably operates at the same frequency as SClk 40 but is preferably offset in phase by an amount specified by the phase input 39, which is preferably an externally programmable parameter. This phase offset allows the relative phase between the modulation signal 16 and the detected response 19 to be adjusted. If the phase is adjusted by some increment, (360/K)°, at the end of each code pattern block or set of blocks the detected response resulting from the modulation signal will preferably be sampled at K discrete phases over K blocks. In this embodiment of the photon measuring system as with the preferred embodiment, the detected response 19 is assumed to be stationary with respect to the start of the code pattern block over that time interval so that the K discrete sampling phases correspond to K discrete sample times and the effective temporal resolution of the sampling process is increased by a factor of K.
This temporal over-sampling is functionally equivalent to the technique described for temporal over-sampling in the A/D converter embodiment. In other embodiments the external phase specification may represent the phase increment rather than the absolute phase, and the generation synchronizer 34 may increment the phase internally.
The preferred implementation of the LFSR 30 is shown in
The preferred functional blocks for the signal detector 10 are shown in
The details of the preferred frame accumulator 50 or 51 are shown in
The details of the preferred frame correlator 55 are shown in
The geometric relationship between the light delivery optics 4, the sample 5, and the detection optics 8 of the preferred photon measurement system 100 depicted in
1. A cost-effective and accurate photon measurement system for human tissue comprising:
- a memory device configured to store a plurality of values corresponding to a plurality of pseudorandom binary code patterns wherein said plurality of values is located by a plurality of cell addresses;
- a code selector configured to select a pseudorandom binary code pattern from said plurality of pseudorandom binary code patterns during operation of said photon measurement system;
- an address sequencer coupled to said memory device and said code selector configured to provide a cell address from said plurality of cell addresses corresponding to said selected pseudorandom binary code pattern;
- a pseudorandom binary code signal generator coupled to the code selector configured to generate a pseudorandom binary code output in accordance with said selected pseudorandom binary code pattern;
- a continuous wave light source coupled to the pseudorandom binary code signal generator configured to generate a pseudorandom binary modulated optical wave modulated in accordance with said pseudorandom binary code output from the pseudorandom binary code signal generator;
- delivery optics coupled to the continuous wave light source to direct the pseudorandom binary modulated optical wave at a human tissue translucent material;
- an optical splitter coupled to the delivery optics between the delivery optics and the translucent material; the optical splitter coupled to an optical detector configured to direct the pseudorandom binary modulated optical wave to the optical detector; the optical detector configured to generate a pseudorandom binary optical reference signal; the optical detector coupled to a signal detector such that when the pseudorandom binary optical reference signal is generated it is communicated to the signal detector;
- a corresponding detector configured to detect scattered optical waves from the translucent material; the corresponding detector having as an output a signal indicative of a characteristic of the detected scattered optical wave; the corresponding detector output signal communicated to the signal detector;
- the signal detector configured to generate and provide an output indicative of a characteristic of the translucent material, based in part on the pseudorandom binary optical reference signal;
- a correlator coupled to the signal detector configured to generate a correlation of said signal indicative of said characteristic of the detected scattered optical wave with said pseudorandom binary optical reference signal; and
- a processor coupled to said correlator configured to calculate photon time-of-flight information of said scattered optical wave based on said correlation.
2. The system of claim 1 further comprising:
- an acquisition synchronizer coupled to the corresponding detector to control acquisition of said signal indicative of said characteristic of the detected scattered optical wave; and
- a synchronization clock coupled to said acquisition synchronizer to control phase of said acquisition synchronizer and wherein the optical splitter is positioned between the continuous wave light source and the delivery optics.
3. The system of claim 1 wherein a first analog to digital converter is positioned between the optical detector and the signal detector to convert the optical reference signal into a digital signal;
- a second analog to digital converter is positioned between the corresponding detector and the signal detector to convert the corresponding detector output signal into a digital detector signal; and
- the signal detector configured to use digital processing techniques to generate the output indicative of the characteristic of the translucent material, based in part on the digitized optical reference signal.
4. The system of claim 1 wherein the signal detector is configured to employ temporal over-sampling to generate and provide the output indicative of the characteristic of the translucent material.
5. The system of claim 1 wherein the pseudorandom binary code pattern represents a single code pattern.
6. The system of claim 1 wherein the pseudorandom binary code pattern represents multiple repeats of a same pattern.
7. The system of claim 1 wherein the pseudorandom binary code pattern is a Gold code pattern.
8. The system of claim 1 wherein the pseudorandom binary code pattern is a Kasami code pattern.
9. The system of claim 1 wherein the pseudorandom binary code pattern is a Walsh code pattern.
10. The system of claim 1 wherein said characteristic of the translucent material is an absorption coefficient.
11. The system of claim 1 wherein said characteristic of the translucent material is a scattering coefficient.
12. The system of claim 1 wherein said characteristic of the translucent material is an absorption coefficient and a scattering coefficient.
13. The system of claim 1 wherein said pseudorandom binary code signal generator comprises a linear feedback shift register.
14. The system of claim 13 wherein said pseudorandom binary code signal generator comprises a gain code input.
15. The system of claim 14 wherein said pseudorandom binary code signal generator comprises a gain code memory.
16. The system of claim 1 further comprising:
- a linear feedback shift register coupled to said memory device.
17. The system of claim 16 further comprising:
- a gain code input coupled to said linear feedback shift register.
18. The system of claim 17 further comprising:
- a gain code memory coupled to said gain code input.
19. The system of claim 1 further comprising:
- a state machine coupled to said memory device.
20. The system of claim 1 wherein said pseudorandom binary code signal generator comprises a state machine.
Filed: Aug 29, 2012
Publication Date: Dec 20, 2012
Applicant: NELLCOR PURITAN BENNETT LLC (Boulder, CO)
Inventors: John F. Heanue (San Jose, CA), Joseph A. Heanue (Oakland, CA), Brian P. Wilfley (Los Altos, CA), Augustus P. Lowell (Durham, NH)
Application Number: 13/598,324
International Classification: A61B 6/00 (20060101);