CN111358473A - Tissue blood flow blood oxygen imaging device and method based on near infrared spectrum - Google Patents
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Abstract
The invention discloses a tissue blood flow and blood oxygen imaging device and method based on near infrared spectrum, which can realize detection and imaging of blood flow and blood oxygen at different depths of a detected tissue. The image forming apparatus includes: the light source is a near-infrared band wavelength coherent laser, the lasers with a plurality of wavelengths are respectively coupled with the multimode optical fiber, and then are sequentially irradiated to the surface of the measured tissue after being switched by the optical switch; the detector is a single-photon counter, the intensity of scattered light spots generated on the surface of the tissue after being irradiated by the light source is detected by using a single-mode optical fiber and converted into electric pulse signals to be sent to an upper computer, and the multi-channel detection optical fiber can realize detection at different positions; the upper computer realizes counting of the electric pulse signals and calculation of light intensity autocorrelation based on a software correlator, attenuation of light intensity with different wavelengths is used for calculating tissue blood oxygen, and meanwhile, the speed of the light intensity autocorrelation attenuation degree is used for calculating tissue blood flow; the position distribution of the light source optical fiber and the detection optical fiber is adjusted to realize the detection and imaging of blood flow and blood oxygen at different depths.
Description
Technical Field
The invention relates to the technical field of biomedical engineering, in particular to a tissue blood flow blood oxygen imaging device and method based on near infrared spectrum.
Background
The parameters of blood flow and blood oxygen of biological tissues are important indexes for measuring whether an organism is normal or not, and the realization of the imaging of the blood oxygen of the tissue blood flow has very important significance for the diagnosis and treatment of brain diseases, breast cancer, cardiovascular diseases and the like.
As the absorption of main chromophores of biological tissues such as water, hemoglobin and fat in a near infrared band is relatively weak, the near infrared spectrum (650nm-950nm) has good penetrability on the biological tissues, and hemoglobin (HbO) of deep biological tissues can be realized2) Deoxyhemoglobin (Hb) and blood oxygen saturation (StO)2) Is generally referred to as near infrared spectroscopy (NIRS). Diffusion Correlation Spectroscopy (DCS) utilizes near infrared Spectroscopy to illuminate the tissue surface by calculating the intensity autocorrelation function (g) of scattered spots on the tissue surface2And tau)), and estimating the motion state of the red blood cells in the tissue, thereby realizing the quantitative detection of the blood flow of the tissue. Among blood flow detection techniques, Laser Doppler (LD) has a low penetration depth, Magnetic Resonance Imaging (MRI) has a low time resolution, and cannot be used for long-term real-time bedside diagnosis, and Positron Emission Tomography (PET) has radiation damage. The diffusion related spectrum technology has the advantages of non-invasive, real-time and long-time bedside detection, low cost, easy operation and the like, and can realize the non-invasive detection of the blood oxygen of the tissue blood flow by combining the near infrared spectrum technology.
At present, the combination of the two technologies is mostly just integrated on a measuring device, and blood flow blood oxygen data of multiple position points is obtained at the cost of increasing the number of channels, so that the cost is high, and the time consumption is long.
Reference to the literature
[1]W.B.Baker,R.Balu,L.He,V.C.Kavuri,D.R.Busch,O.Amendolia,F.Quattrone,S.Frangos,E.Maloney-Wilensky,K.Abramson,E.Mahanna Gabrielli,A.G.Yodh,and W.Andrew Kofke,"Continuous non-invasive optical monitoring ofcerebral blood flow and oxidative metabolism after acute brain injury,"J.Cereb.Blood Flow Metab.39(8),1469–1485(2019).
[2]D.Wang,A.B.Parthasarathy,W.B.Baker,K.Gannon,V.Kavuri,T.Ko,S.Schenkel,Z.Li,Z.Li,M.T.Mullen,J.A.Detre,and A.G.Yodh,"Fast blood flowmonitoring in deep tissues with real-time software correlators,"Biomed.Opt.Express 7(3),776(2016).
[3]T.Dragojevic′,J.L.Hollmann,D.Portaluppi,M.Buttafava,D.Tamborini,J.P.Culver,F.Villa,and T.Durduran,"Compact,low power consumption and low costmulti-exposure speckle contrast optical spectroscopy(SCOS)device for real-time measurement of deep tissue blood flow,"Opt.InfoBase Conf.Pap.Part F91-T(1),798–808(2018).
[4]D.Tamborini,P.Farzam,B.Zimmermann,K.-C.Wu,D.A.Boas,andM.A.Franceschini,"Development and characterization of a multidistance andmultiwavelength diffuse correlation spectroscopy system,"Neurophotonics 5(01),1(2017).
Disclosure of Invention
The invention provides a tissue blood flow blood oxygen imaging device and method based on near infrared spectrum, and aims to provide a solution with reasonable design, low cost, convenience and quickness on the basis of combining diffusion related spectrum and near infrared spectrum technology. The device gives consideration to the number of channels and the measurement time, can flexibly change the arrangement distribution of the light source optical fibers and the detection optical fibers in the measurement probe, and can complete the simultaneous imaging of blood flow and blood oxygen parameters of tissues to be measured at different depths.
See the description below for details:
a tissue blood flow blood oxygen imaging device and method based on near infrared spectrum, the device comprises:
(1) the light source is a long coherent laser with near infrared band and different wavelengths, which is respectively coupled with multimode fibers by NA× 1 switching the wavelength of light source after the switch A, then passing through 1 × NBAnd the road light switch B is switched to different light source point positions on the measuring probe to complete the switching of the light source position points.
(2) The detector is a single photon counter, is used for receiving the scattered light spot intensity on the surface of the measured tissue body after being irradiated by the light source, is coupled with the single-mode optical fiber and passes through NC× 1 path optical switch C for counting photons at different positions and converting light intensity signal into light intensity signalAn electrical pulse signal.
(3) The upper computer realizes the counting of the electric pulse signals and the light intensity normalization autocorrelation (g) based on the software correlator2(τ)) and then normalizing the autocorrelation (g) based on the attenuation of the intensity of the light at different wavelengths and the intensity of the light2(τ)) to perform the computation and imaging of blood oxygen and blood flow parameters, respectively.
(4) The measuring probes are distributed with light source fiber probes and detecting fiber probes, and can realize the imaging of blood flow and blood oxygen parameters according to the distance of the probes and different depths.
The upper computer realizes counting of electric pulse signals and calculation of light intensity autocorrelation, the attenuation of light intensity with different wavelengths can be used for calculating the concentration of tissue oxyhemoglobin and deoxyhemoglobin, the blood oxygen saturation and the light intensity normalization autocorrelation (g)2(tau)) the speed of attenuation degree represents the dynamic characteristics of the medium in the tested tissue, and can be used for calculating the blood flow of the tissue and completing blood flow oximetry imaging.
Furthermore, the light source is a long coherent laser with different wavelengths in a near infrared band, the power is more than 50mW, the coherence length is more than 10m, the wavelength range is 650nm-950nm, the central wavelength can be 685nm, 785nm or 830nm, and the light is transmitted through the multimode fiber.
Furthermore, the light source optical fiber is a multimode optical fiber, and the core diameter is 50 μm, 62.5 μm, 100 μm or more.
Furthermore, the detection optical fiber is a single-mode optical fiber, and the core diameter is 5 μm or 9 μm.
Furthermore, the upper computer comprises a software correlator for counting and autocorrelation operation of the electric pulse signals input by the single photon counter, and the upper computer calculates the oxygen-containing hemoglobin concentration, the deoxyhemoglobin concentration, the blood oxygen saturation and the blood flow data according to the light intensity attenuation data obtained by counting the electric pulses and the light intensity normalized autocorrelation attenuation data, and finally completes the imaging of the blood oxygen parameters.
Further, the calculation formula of the blood oxygen saturation degree is as follows:
in the formula, CHbO2For oxyhemoglobin concentration, CHbIs the concentration of deoxyhemoglobin.
Further, the light intensity normalized autocorrelation (g) of the present invention2(τ)) the calculation formula is:
where I (t) represents the detected intensity at time t, τ is the delay time, and < > represents the time averaging.
Advantageous effects
The invention provides a tissue blood flow blood oxygen imaging device and method based on near infrared spectrum, which realize the switching of light source wavelength and light source position points by utilizing an optical switch, after a light source irradiates the surface of a measured tissue through the conduction of a multimode optical fiber, a scattered light spot on the surface of the tissue is detected through a single photon counter, an optical signal is converted into an electric pulse signal to realize the acquisition of light intensity and normalization autocorrelation, blood flow and blood oxygen data are obtained through conversion, and the imaging of blood flow and blood oxygen of different depths of the measured biological tissue can be realized according to the difference of the distances between a light source probe and a detection probe.
Drawings
FIG. 1 is a schematic diagram of a tissue blood flow oximetry imaging device system based on near infrared spectroscopy;
FIG. 2 is a schematic diagram showing the arrangement and distribution of source fibers and detection fibers in a measurement probe;
in the drawings, the components represented by the respective reference numerals are listed below:
1: long coherent laser (685nm) 2: long coherent laser (785nm)
3: long coherent laser (830nm) 4: optical switch A
5: optical switch B6: measuring probe
7: the measured tissue 8: optical switch C
9: a single photon counter 10: photon correlator (software correlator)
11: an upper computer 12: light source optical fiber
13: the detection optical fiber 14: cable with a protective layer
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention are described in further detail below with reference to the accompanying drawings in conjunction with specific embodiments.
The invention provides a tissue blood oxygen imaging device based on near infrared spectrum, fig. 1 shows a system block diagram of the tissue blood oxygen imaging device based on near infrared spectrum, the device comprises:
long coherent lasers (1), (2) and (3) in the near infrared band, the central wavelength of which can be chosen between 650nm and 950nm, the coherence length being greater than 10m and the power being greater than 50 mW. In the embodiment of the present disclosure, the central wavelengths of the lasers are 685nm, 785nm and 830nm, and other wavelengths may be selected according to actual requirements, or the number of wavelengths may be increased.
The optical switch A (4) is NA× 1 route optical switch, wherein NAFor the number of lasers, satisfy NANot less than 2. The optical switch a completes the switching among the plurality of lasers, namely, the wavelength of the light source is switched, and a single-wavelength light source is output to the optical switch B.
The optical switch B (5) is 1 × NBRoad light switch, wherein NBThe number of the light source probes is 12 in the embodiment of the present disclosure, as shown in fig. 2, N may also be increased or decreased according to actual requirementsBThe number of (2).
The measuring probe (6) is used for arranging the distributed light source probe and the detecting probe, and the arrangement distribution schematic diagram is shown in figure 2, wherein
Representing a light source probe, ● representing a probe. In the embodiment of the present disclosure, the probing probes are distributed in a circle with the center as a specific embodiment, the probing probe located at the center has 6 light source probes distributed with a radius of 10mm, and has 6 light source probes distributed with a radius of 20mm, and the 6 light source probes in the latter also have a probing probe with a distance of 10mm from the paired probing probes. Namely, 6 light source probes with the distance of 10mm and 6 light source probes with the distance of 20mm are distributed around each probe. The arrangement of the probes in the embodiment of the disclosure is only used as a specific embodiment, and the number of the probes can be increased or decreased according to actual requirements, so as to increase or decrease the imaging range.
The biological tissue (7) to be tested is, but not limited to, a human body part such as a brain, a breast, a skeletal muscle, etc.
The optical switch C (8) is NC× 1 route optical switch, wherein NCIn the embodiment of the present disclosure, the number of the light source probes is 12 for detecting the number of the probes, as shown in fig. 2, N may be increased or decreased according to actual requirementsCThe number of (2).
And the single photon counter (9) is used for receiving the scattered light spot intensity on the surface of the detected tissue body after being irradiated by the light source, recording the photon number and converting the photon number into a TTL electric pulse signal.
A photon correlator (10) for performing light intensity normalized autocorrelation (g)2(τ)) is calculated.
An upper computer (11) for correlating the light intensity with the normalized autocorrelation (g)2And (tau)) converting to obtain blood flow and blood oxygen data, and realizing the imaging of blood flow and blood oxygen at different depths of the detected biological tissue according to the different distances between the light source probe and the detection probe.
The light source fiber (12) is a multimode fiber having a core diameter of 50 μm, 62.5 μm, 100 μm or more.
The detection fiber (13) is a single mode fiber, and the core diameter is 5 μm or 9 μm, but is not limited to the above two.
And a cable (14) for data transmission.
Furthermore, the invention also provides a tissue blood flow blood oxygen imaging method based on the near infrared spectrum, and the device can be used for completing the imaging of the blood flow blood oxygen of the tested tissue. The method comprises the following specific steps:
the method comprises the following steps: fixing the measuring probe on the surface of the measured tissue, determining the required position points of the light source probe and the detecting probe according to requirements, and setting the switching of the optical switch in the upper computer. And (3) turning on the laser, completing wavelength switching and position switching through the optical switch A and the optical switch B, and transmitting and irradiating to a position point required by the measured tissue through the optical source fiber.
Step two: and the single photon counter detects the intensity of the scattered light spot at the corresponding position point through the switching of the optical switch C, counts the scattered photons at the position point and outputs a TTL electric pulse signal.
Step three: the upper computer calculates the electric pulse signals transmitted in the second step to obtain light intensity normalized autocorrelation (g)2(τ)), the attenuation of the light intensity at different wavelengths can be used to calculate oxyhemoglobin concentration and deoxyhemoglobin concentration, thereby calculating blood oxygen saturation, the light intensity normalized autocorrelation (g)2(τ)) may be used to calculate the Brownian scattering coefficient (D)b) And calculating the blood flow parameters. After the data detection processing of all the measuring positions is completed, the upper computer realizes the imaging of the blood flow blood oxygen of different depths of the measured biological tissue according to the different distances between the light source probe and the probe.
Further, the tissue blood flow blood oxygen imaging device and method based on near infrared spectrum of the invention utilize the double wavelength near infrared light to the oxygen-containing hemoglobin concentration, the deoxyhemoglobin concentration, the blood oxygen saturation and the blood flow to calculate specifically as follows:
for the electric pulse signals obtained in the step three, namely the light intensity signals I (t) at different moments, the oxyhemoglobin concentration is adjusted according to the modified Lambert beer law
And deoxyhemoglobin concentration (C)Hb) The variation calculation formula is as follows:
wherein the content of the first and second substances,
for oxyhemoglobin concentration change, Δ CHb(t) is the change in the concentration of deoxyhemoglobin,
respectively represents oxyhemoglobin and deoxyhemoglobin at wavelength lambda1And λ2The lower corresponding molar extinction coefficient, I (. lamda.)1T) and I (λ)2And t) respectively represent at a wavelength of λ1And λ2Light intensity at time t, Lλ1(t) and
respectively represent the wavelength lambda1And λ2The corresponding path difference factor.
Therefore, the blood oxygen saturation (StO)2) Is calculated by
Can be converted into:
in the formula (I), the compound is shown in the specification,
for oxyhemoglobin concentration, CHbIn order to obtain the concentration of the deoxygenated hemoglobin,
and CHb(0) Respectively representing the oxyhemoglobin concentration and the deoxyhemoglobin concentration at the initial time (i.e., when t is 0), which can be calculated by the absorption coefficient of the human body.
Meter for blood flowHowever, intensity normalized autocorrelation (g) has been introduced above2(τ)) the calculation formula is:
wherein I (t) represents the detected light intensity at time t, τ is the delay time,<>the representations are averaged over time. DbDependent on the correlation function g for the Brown scattering coefficient2Blood Flow factor (BFI) BFI ≡ α DbWherein α is between 0 and 1 and represents the proportion of the moving scattering particles to all particles in the biological tissue.
The relationship between Blood Flow (BF) and blood flow factor (BFI) is as follows:
BF＝γBFI
wherein BF is a blood flow and is expressed as mL 100mL-1·min-1(ii) a BFI is a blood flow factor in cm2S; gamma is a proportionality constant in units of (mL 100 mL)-1·min-1)/(cm2/s)。
The formula for calculating relative blood flow (rBF) is as follows:
wherein, BF0And BFI0Representing blood flow and blood flow factors, respectively, at the initial time.
When the light source wavelength is three or more, the oxyhemoglobin concentration
And deoxyhemoglobin concentration (C)Hb) The variation calculation formula is as follows:
wherein the content of the first and second substances,
for oxyhemoglobin concentration change, Δ CHb(t) is the change in the concentration of deoxyhemoglobin,
respectively represents oxyhemoglobin and deoxyhemoglobin at wavelength lambda1And λnThe lower corresponding molar extinction coefficient, I (. lamda.)1T) and I (λ)nAnd t) respectively represent at a wavelength of λ1And λnThe light intensity at the time t,
and
respectively represent the wavelength lambda1And λnThe corresponding path difference factor.
The rest steps are completely the same as the calculation of the dual-wavelength light source, and the calculation result can be more accurate through the calculation of the multi-wavelength light source.
The probe of the device can be used for measuring at different positions to be measured, and calculating and imaging the blood flow blood oxygen of different areas of a human body.
Finally, it should be noted that although the present invention has been described with reference to the preferred embodiments, it should be understood by those skilled in the art that the above-mentioned preferred embodiments are merely illustrative of the present invention and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and scope of the present invention should be included in the scope of the present invention.
Claims (10)
1. A tissue blood flow blood oxygen imaging device based on near infrared spectrum is characterized by comprising: the device comprises a light source, an optical switch A (4), an optical switch B (5), a measuring probe (6), an optical switch C (8), a detector (9), a photon correlator (10), an upper computer (11), a light source optical fiber (12) and a detection optical fiber (13);
the light source is a plurality of long coherent lasers with different wavelengths in near-infrared wave bands, is coupled with a light source optical fiber (12), is connected with a measuring probe (6) after being switched by an optical switch A (4) and an optical switch B (5) in sequence, and irradiates the surface of the tissue body;
the optical switch A (4) is used for completing the switching among the plurality of long coherent lasers, namely the wavelength switching of a light source; the optical switch B (5) is used for switching the light source with a certain wavelength screened by the optical switch A (4) to different position points on the surface of the tissue, namely switching the position of the light source;
the measuring probe (6) is placed on the surface of the tissue body and used for arranging and distributing the light source probes and the detecting probes, and different probes are arranged and distributed and used for measuring blood flow and blood oxygen data at different depths;
the optical switch C (8) inputs the detector optical fibers (13) with different position points, and outputs the detector optical fibers to be connected with the detector (9) to realize detection of different position points on the surface of the tissue body, namely detection position switching;
the detector (9) is a single photon counter, is used for receiving the scattered light spot intensity on the surface of the detected tissue body after being irradiated by the light source, is coupled with the detection optical fiber (13), and realizes photon counting on different position points through the optical switch C (8);
the photon correlator (10) is a software module of an upper computer and completes light intensity normalization autocorrelation (g) according to the output of the detector (9)2(tau)) and converting the signals into electric pulse signals to be transmitted to an upper computer;
the upper computer (11) realizes counting of the electric pulse signals and light intensity normalization autocorrelation (g) based on a software correlator2(τ)) and blood flow oximetry imaging.
2. The near infrared spectroscopy-based tissue blood flow oximetry imaging device according to claim 1, wherein the long coherent laser has a coherence length of 10m or more, a wavelength range of 650nm to 950nm, and a center wavelength of 685nm, 785nm or 830 nm.
3. The near infrared spectroscopy-based tissue blood flow oximetry imaging device of claim 1, wherein optical switch A (4) is NA× 1 route optical switch, wherein NA≥2。
4. The near infrared spectroscopy-based tissue blood flow oximetry imaging device of claim 1, wherein optical switch B (5) is 1 × NBRoad light switch, wherein NBThe number of the light source probes.
5. The near infrared spectroscopy-based tissue blood flow oximetry imaging device of claim 1, wherein the optical switch C (8) is NC× 1 route optical switch, wherein NCThe number of the probe heads is adopted.
6. The device as claimed in claim 1, wherein the light source fiber (12) is a multimode fiber with a core diameter of 50 μm, 62.5 μm, 100 μm or more.
7. The device as claimed in claim 1, wherein the detection fiber (13) is a single mode fiber with a core diameter of 5 μm.
8. The tissue blood oxygen imaging method based on the near infrared spectrum is the tissue blood oxygen imaging device based on the near infrared spectrum, and is characterized by comprising the following steps of:
(1) multiple near infrared band long coherent laser and N through light source optical fiberA× 1 the optical switches A are connected to complete the wavelength switching, and then the wavelength is switched through 1 × NBThe path light switch B completes the switching of the position points of the light source probe and finally irradiates the surface of the tissue to be measured in sequence;
(2) after the light source in the step (1) irradiates, the detector detects the intensity of scattering light spots on the surface of the detected tissue, converts the intensity into an electric pulse signal and transmits the electric pulse signal to an upper computer;
(3) the upper computer performs light intensity normalization autocorrelation (g) by counting the electric pulse signals2(τ)) and the attenuation of the light intensity at different wavelengths is used to calculate oxygenated hemoglobinWhite concentration and deoxyhemoglobin concentration, thereby calculating blood oxygen saturation, and light intensity normalization autocorrelation (g)2(τ)) may be used to calculate the Brownian scattering coefficient (D)b) The calculation of blood flow parameters is realized, and blood flow blood oxygen imaging is finally completed;
wherein the light intensity normalizes the autocorrelation (g)2(τ)) is:
in the formula, I (t) represents the detected light intensity at t moment, tau is delay time, and < > represents the average of time;
(4) the distance between the light source probe and the detection probe is changed to realize detection of different depths.
9. The method of claim 8, wherein the Blood Flow (BF) is calculated by the following formula:
BF＝γBFI
wherein BF is a blood flow and is expressed as mL 100mL-1·min-1(ii) a BFI is a blood flow factor in cm2S; gamma is a proportionality constant in units of (mL 100 mL)-1·min-1)/(cm2S), Blood Flow factor (BFI) BFI ≡ α DbWherein α is between 0-1 and represents the ratio of the moving scattering particles to all particles in the biological tissue, DbDependent on the correlation function g for the Brown scattering coefficient2(τ) exponential decay rate.
10. The method of claim 8, wherein the blood oxygen saturation level (StO) is based on near infrared spectroscopy2) The calculation formula of (2) is as follows:
in the formula，
For oxyhemoglobin concentration, CHbIs the concentration of deoxyhemoglobin.
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