CN110974205B - Large-field-of-view multi-modal imaging system - Google Patents
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Abstract
The invention provides a large-field-of-view multi-modal imaging system, which comprises: an illumination subsystem; an infinity relay imaging subsystem; and the data processing subsystem is used for calculating the blood flow velocity of the area to be measured according to the speckle signal received by the image sensor, calculating the hemoglobin concentration of the area to be measured according to the reflected light intensity signal received by the image sensor, and registering and calculating the relative oxygen metabolic rate according to the obtained blood flow velocity and the hemoglobin concentration. According to the large-view-field multi-modal imaging system, the infinite relay imaging subsystem is added, so that the light splitting component can be conveniently inserted into the relay subsystem, more imaging light paths are provided, the light source does not need to be switched, the data acquisition of the blood flow speed and the hemoglobin concentration is realized, and the real-time large-view-field multi-modal tissue hemodynamic parameter monitoring is facilitated.
Description
Technical Field
The invention relates to the technical field of medical equipment, in particular to a large-view-field multi-modal imaging system.
Background
Monitoring hemodynamic parameters of the tissue such as blood flow, blood oxygen, blood volume, etc. simultaneously has important clinical significance in assessing physiological or pathological conditions.
In the related technology, the fluctuation of a dynamic speckle pattern is analyzed by a laser speckle blood flow imaging technology to calculate the relative blood flow, so that the method has the advantages of real time, full field and non-contact, and has wide clinical application. There is a report in the literature that other technologies such as LSCI (Laser speckle signal), ois (optical internal signal imaging), and fluorescence imaging technology are combined to realize multi-modal monitoring of hemodynamic signals.
However, for obtaining clinical macroscopic information, most of the currently used large-field-of-view camera lenses have standard interfaces such as C port and F port, and since the working distance is short and is not enough to insert a light splitting or filtering element, most of the currently used camera lenses are realized by switching light sources, which greatly reduces the time resolution of an imaging system and is not beneficial to real-time large-field multi-modal tissue hemodynamic parameter monitoring.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. Therefore, an object of the present invention is to provide a large-field-of-view multi-modal imaging system, which has a large rear working distance of an objective lens, facilitates the insertion of a light splitting element, can improve the time resolution of the imaging system, and facilitates the real-time monitoring of the large-field-of-view multi-modal tissue hemodynamic parameters.
In order to achieve the above object, a large-field multi-modality imaging system according to an embodiment of a first aspect of the present invention includes: the illumination subsystem is used for providing a laser beam and an LED beam and coupling the laser beam and the LED beam into a detection beam, and the detection beam irradiates an area to be detected of a sample to generate a speckle signal and a reflected light intensity signal; the infinity relay imaging subsystem sequentially comprises an objective lens, a main relay lens group, a light splitting component, a plurality of auxiliary relay lens groups and image sensors which are respectively arranged corresponding to each auxiliary relay lens group; the primary relay lens group collects detection light beams carrying speckle signals and reflected light intensity signals through the objective lens; the detection light beam is split into a laser light beam carrying speckle signals and an LED light beam carrying reflected light intensity signals after passing through the light splitting assembly, and the laser light beam carrying the speckle signals and the LED light beam carrying the reflected light intensity signals are received by corresponding image sensors after passing through different secondary relay lens groups respectively; and the data processing subsystem is used for calculating the blood flow velocity of the area to be measured according to the speckle signal received by the image sensor, calculating the hemoglobin concentration of the area to be measured according to the reflected light intensity signal received by the image sensor, and registering and calculating the relative oxygen metabolic rate according to the obtained blood flow velocity and the hemoglobin concentration.
The large field of view multi-modality imaging system according to embodiments of the present invention, by adding an infinity relay imaging subsystem, a main relay lens group and a plurality of auxiliary relay lens groups are arranged between the objective lens of the subsystem and the image sensor, the working distance behind the objective lens can be increased, the light splitting component can be conveniently inserted, the system can be conveniently expanded, the laser beam carrying speckle signals and the LED beam carrying reflected light intensity signals can be obtained through the image sensor, the data processing subsystem calculates the blood flow velocity of the area to be measured according to the speckle signals received by the image sensor, and calculating the concentration of hemoglobin according to the received reflected light intensity signal, and obtaining the relative oxygen metabolic rate according to the registration calculation of the obtained blood flow velocity and the hemoglobin concentration, so that the detection of the blood flow velocity, the hemoglobin concentration and the relative oxygen metabolic rate is realized, and the real-time large-field multi-modal tissue hemodynamic parameter monitoring is facilitated.
In some embodiments, the image sensor used by the large-field-of-view multi-modal imaging system to acquire the speed of laser light carrying speckle signals is a monochrome camera.
In some embodiments, the data processing subsystem calculates the blood flow velocity of the region to be measured by using a laser speckle contrast imaging method, and a mathematical formula of a contrast K and the blood flow velocity v is as follows:
wherein, taucIs the electric field decorrelation time, T is the exposure time, beta is a quantity related to the detector size, the speckle size and the polarization, v is the blood flow velocity, and the relationship between the velocity v and the contrast K can be approximately expressed as v ^ 1/K2(ii) a The contrast K is calculated through a spatial sliding window:
In some embodiments, the LED light beams include a red light beam and a green light beam, and the image sensor for collecting the LED light beams carrying the reflected light intensity signals is a color camera.
In some embodiments, the extinction ratio and hemoglobin concentration difference between time 0 and time t are related according to lambert beer's law as:
log(R0/Rt)＝(εHbO(λ)ΔcHbO+εHbR(λ)ΔcHbR)Da(λ)；
wherein R is0,RtTissue reflection light intensity at 0 moment and t moment respectively; epsilonHbO(λ),εHbR(λ) are molar extinction coefficients of HbO (oxygenated Hemoglobin concentration) and HbR (oxygenated Hemoglobin concentration), respectively, at a wavelength λ; Δ cHbOAnd Δ cHbRIs the concentration difference between the time t and the time 0; da(λ) is a differential path factor, obtainable by monte carlo simulation in combination with the optical properties of biological tissue; the data processing subsystem collects a reflected light intensity signal V in a red channel or a blue channel of the color camera, substitutes the reflected light intensity signal V into the following formula, and calculates r (lambda) and L (lambda): v ═ m ═ R (λ) L (λ) d λ; wherein R (lambda) is the spectral response of the channel, R (lambda) is the tissue reflected light intensity, L (lambda) is the light source spectral distribution, and m is the proportionality coefficient; and calculating the hemoglobin concentration by the following formula:
cHbT＝cHbO+cHbR(ii) a Wherein, VB,0,VB,tThe reflected light intensity signals V and V measured by the blue channel at the time 0 and the time t respectivelyR,0,VR,tThe reflected light intensity signals epsilon measured by the red channels at the time 0 and the time t respectivelyHbO(λ),εHbR(λ) are the molar extinction coefficients of the oxygenated and deoxygenated hemoglobin concentrations, respectively, at a wavelength λ; Δ cHbOIs the difference in oxygenated hemoglobin concentration between time t and time 0, Δ cHbRIs the difference in the concentration of deoxygenated hemoglobin between time t and time 0; da(λ) is the differential path factor, mB,mRThe proportionality coefficients for the blue and red channels, respectively, can be calculated from the baseline conditions in combination with Lambert beer's lawB(λ),rR(λ) is the spectral response of the blue and red channels, respectively; l isg(λ),Lr(lambda) spectral distributions of the green and red beams, CHbTAs total hemoglobin concentration, CHbOIs the concentration of oxygenated hemoglobin, CHbRIs the deoxyhemoglobin concentration.
In some embodiments, the baseline for oxygenated hemoglobin concentration is set at 60Um and the baseline for deoxygenated hemoglobin concentration is set at 40 Um.
In some embodiments, the data processing subsystem calculates the relative oxygen metabolism rate by the formula:
wherein, rMRO2Is the relative oxygen metabolic rate, gammaR,γTFor the vessel weighting factor, set to 1, v for simplified calculationBF,0、ΔvBFBlood flow velocity and amount of change in blood flow velocity at time 0, cHbR,0、ΔcHbRThe respective amounts of change of the deoxyhemoglobin concentration and the deoxyhemoglobin concentration at 0 time, cHbT,0、ΔcHbTThe total hemoglobin concentration and the amount of change in the total hemoglobin concentration at time 0.
In some embodiments, the illumination subsystem comprises: a laser light source for providing the laser beam; an LED light source for providing the LED light beam; a dichroic mirror for coupling the laser beam and the LED beam into a detection beam; and the beam expander is arranged on the light emergent path of the dichroic mirror and used for increasing the irradiation area of the detection light beams.
In some embodiments, the large field of view multi-modality imaging system further comprises: and the liquid focusing lens is arranged between the objective lens and the main relay lens group and is used for adjusting a relay imaging focal plane of the main relay lens group.
In some embodiments, the light splitting assembly comprises: the multi-path light splitting lens group is arranged between the main relay lens group and the auxiliary relay lens group, is arranged at a preset angle, and is used for splitting the detection light beams into multiple paths to be transmitted to different auxiliary relay lens groups; and the filter is arranged between the auxiliary relay lens group and the multi-path light splitting lens group and used for filtering stray light.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a schematic diagram of a large field of view multi-modality imaging system, according to one embodiment of the present invention;
FIG. 2 is a schematic diagram of a relay imaging subsystem according to one embodiment of the present invention;
FIG. 3 is a schematic diagram of RGB channel spectral response curves and LED light, e.g., distribution curves, according to one embodiment of the present invention;
FIG. 4 is a schematic diagram of the basic flow of data processing by the data processing subsystem according to one embodiment of the present invention;
FIG. 5 (a) is a schematic diagram showing a hemoglobin drop-wise addition result of a phantom experiment according to an embodiment of the present invention;
FIG. 5 (b) is a graph showing the results of an experiment in which the oxygen content of the mimetibody is changed;
FIG. 6 (a) is a schematic diagram of a cuff-pressurized forearm experiment showing two-dimensional plots of the relative changes in rBF, HbO, HbR, HbT, rMRO2 at different times in accordance with one embodiment of the present invention;
FIG. 6 (b) is a graph showing the time-dependent profiles of rBF, HbO, HbR and HbT in the ROI region;
FIG. 6 (c) is a schematic of a plot of rMRO2 over time within the ROI area;
FIG. 7 (a) is a graphical representation of the results of the PBV and SPG monitoring experiments tested in accordance with one embodiment of the present invention;
fig. 7 (b) is a schematic diagram of signal amplification for one cycle;
fig. 7 (c) is a schematic diagram of a time delay histogram distribution in 40 s;
FIG. 7 (d) is a diagram illustrating the mean statistics of the 4 tested time delays;
fig. 7 (e) shows a schematic diagram of a local picture and ROI acquired by the system.
Detailed Description
Embodiments of the present invention will be described in detail below, the embodiments described with reference to the drawings being illustrative, and the embodiments of the present invention will be described in detail below.
A large field of view multi-modality imaging system in accordance with an embodiment of the first aspect of the invention is described below with reference to fig. 1.
According to the large-view-field multi-modal imaging system, the infinite relay imaging subsystem is added, so that light splitting or filtering elements are added in a relay light path, an imaging light source does not need to be switched, the time resolution of the imaging system is high, real-time monitoring of multi-modal hemodynamic parameters is facilitated, expansion of the system is facilitated, and more diverse hemodynamic parameters are facilitated to be monitored.
Fig. 1 is a schematic diagram of a large-field multi-modality imaging system according to an embodiment of the present invention, and as shown in fig. 1, a large-field multi-modality imaging system 20 of an embodiment of the present invention includes an illumination subsystem 30, an infinity relay imaging subsystem 40, and a data processing subsystem (not shown).
The illumination subsystem 30 is configured to provide a laser beam and an LED beam and couple the laser beam and the LED beam into a detection beam, and the detection beam irradiates an area to be detected of a sample and then generates a reflected light, where spatial distribution and temporal change of the reflected light are used as speckle signals, and wavelength change of the reflected light is used as a reflected light intensity signal; the infinity relay imaging subsystem 40 comprises an objective lens 410, a primary relay lens group 420, a light splitting assembly 430, a plurality of secondary relay lens groups 440 and 450, and image sensors 460 and 470 respectively corresponding to each secondary relay lens group, wherein the primary relay lens group 420 collects detection light beams carrying speckle signals and reflected light intensity signals through the objective lens 410; the detection light beam is split into a laser light beam carrying the speckle signal and an LED light beam carrying the reflected light intensity signal after passing through the light splitting assembly 430, and the laser light beam carrying the speckle signal and the LED light beam carrying the reflected light intensity signal are received by the corresponding image sensors after passing through different secondary relay lens groups respectively. The data processing subsystem is used for calculating the blood flow speed of the area to be measured according to the speckle signals received by the image sensor, calculating the hemoglobin concentration of the area to be measured according to the reflected light intensity signals received by the image sensor, and registering and calculating the relative oxygen metabolic rate according to the obtained blood flow speed and the hemoglobin concentration.
Specifically, fig. 2 illustrates the infinity relay imaging subsystem 40, which sequentially includes a camera lens 410, a primary relay lens group 420, a light splitting assembly 430, a plurality of secondary relay lens groups 440 and 450, and image sensors 460 and 470 corresponding to each of the secondary relay lens groups; any one of the secondary relay lens groups 440, 450 is parallel to the primary relay lens group 420 and forms a relay imaging lens group. The primary relay lens group and the secondary relay lens group respectively comprise a tri-cemented lens 110 and 130 and a negative meniscus lens 120 and 140 from the mirror image side to the outer side, the tri-cemented lens comprises a double convex lens and meniscus lenses symmetrically arranged at two sides of the double convex lens, and the negative meniscus lens protrudes towards one side far away from the tri-cemented lens.
The negative meniscus lens 120 is disposed on the incident path of the triplet 110, the concave surface of the negative meniscus lens 120 adjacent to the primary relay lens group faces the triplet 110 side, and the negative meniscus lens 140 adjacent to the triplet 130 is disposed on the light exit path of the secondary relay lens group 130. And, the tri-cemented lens 110,130 may be composed of one or more achromatic lenses, for example, the focal lengths of the tri-cemented lens 110 and the tri-cemented lens 130 are both 50mm, and the focal lengths of the two negative meniscus lenses are-150 mm. And the primary relay lens group 420 and the secondary relay lens groups 440 and 450 are symmetrically arranged to form a 1:1 relay imaging subsystem.
The parameters of the primary relay lens group are shown in table 1, and the parameters of the secondary relay lens group are symmetrical to the parameters.
TABLE 1
| Noodle | Radius of curvature (mm) | Thickness (mm) | Refractive index | Coefficient of dispersion | ||
| Negative meniscus | S1 noodle | 100 | 3 | 1.5168 | 64.1673 | |
| S2 noodle | 43.1 | 22 | ||||
| Triple cemented lens | S1 noodle | 31.25 | 6.4 | 1.8011 | 34.9739 | |
| S2 noodle | 18.47 | 13 | 1.5168 | 64.1673 | ||
| S3 noodle | -18.47 | 6.4 | 1.8011 | 34.9739 | ||
| S4 noodle | -31.25 |
The distance between the two negative meniscus lenses is 19-35 mm, and 22mm can be selected in consideration of the flange distance and the resolution capability of the C-port lens as the objective lens. The distance between the main relay imaging lens and the auxiliary relay imaging lens can be adjusted as required, but the relay distance is mainly limited by the aperture of the lens, and according to the simulation result, if a lens with the aperture of 25.4mm is used, the longest relay distance can reach 180 mm. As the relay distance continues to increase, vignetting occurs, resulting in a decrease in imaging distance, and in order to achieve high imaging quality, a relay distance of 60mm, for example, may be selected, and the relay imaging lens only uses two lenses, which facilitates processing and adjustment.
In some embodiments, the negative meniscus lens has a refractive index of 1.5168 and an abbe number of 64.1673, the double convex lens has a refractive index of 1.5168 and an abbe number of 64.1673, the meniscus lens has a refractive index of 1.8011 and an abbe number of 34.9739, and good-quality imaging can be achieved.
In some embodiments, the negative meniscus lens has a radius of curvature of 100mm for the S1 face and 43.1mm for the S2 face; the radius of curvature of the S3 surface of the tri-cemented lens is 31.25mm, the radius of curvature of the S4 surface is 18.47mm, the radius of curvature of the S5 surface is-18.47 mm, and the radius of curvature of the S6 surface is-31.25 mm.
The primary relay lens group 420 of the infinity relay imaging subsystem 40 collects the detection light beam carrying the speckle signal and the internal source detection signal through the objective lens 410, the detection light beam is divided into two paths after passing through the light splitting assembly 430, an image sensor 460 corresponding to the secondary relay lens group 440 receives the laser beam carrying the speckle signal, the image sensor 470 corresponding to the other set of secondary relay lenses 450 receives the LED light beam carrying the reflected light intensity signal, the data processing subsystem calculates the blood flow velocity of the region to be measured according to the speckle signal received by the image sensor 460, and calculating the hemoglobin concentration of the region to be measured according to the reflected light intensity signal received by another image sensor 470, obtaining the blood flow velocity and the hemoglobin concentration, registering to obtain the relative oxygen metabolic rate, therefore, the blood flow speed and the hemoglobin concentration are monitored in real time, and data support is provided for the evaluation of the physiological or pathological state of the sample.
According to the large-view-field multi-modal imaging system 20 provided by the embodiment of the invention, by adding the infinite relay imaging subsystem 40 and arranging the main relay lens group 420 and the plurality of auxiliary relay lens groups between the objective lens 410 and the image sensor of the subsystem, the light splitting component 430 is convenient to insert, laser beams and LED beams carrying reflected light intensity signals are obtained through the image sensor, the blood flow speed of the region to be detected is calculated according to speckle signals received by the image sensor, the hemoglobin concentration is calculated according to the received reflected light intensity signals, the data acquisition of the blood flow speed and the hemoglobin concentration is realized, and the real-time large-view-field multi-modal tissue hemodynamic parameter monitoring is facilitated.
In some embodiments, as shown in fig. 1, the illumination subsystem 30 includes: the laser light source 310 is used for providing a laser beam; an LED light source 320 for providing the LED light beam; dichroic mirror 330 is used to couple the laser beam and the LED beam into a detection beam; the beam expander 340 is disposed on the light exit path of the dichroic mirror 330, and is configured to increase the irradiation area of the detection light beam.
Specifically, the laser light source 310 is selected from many, for example, the laser light source 310 may be a near-infrared laser. In order to reduce crosstalk between channels, the LED light source 320 may select a mixed light source including a red light beam and a green light beam, and the image sensor 470 may select a blue channel value and a red channel value having smaller spectral response curve aliasing for calculation, as shown in fig. 3, and a white disc is used as a sample to test the system crosstalk, and when the red light beam is irradiated, the ratio of the red channel value to the blue channel value is 13.94, and when the green light beam is irradiated, the ratio of the blue channel value to the red channel value is 7.66. At this time, after the laser light source 310 and the LED light source 320 are coupled through the first dichroic mirror 330, and then pass through the beam expander 340, the beam expander 340 makes the coupled detection light beam sufficiently cover the field of view.
In some embodiments, as shown in fig. 2, the large field of view multi-modality imaging system 20 further includes a liquid focus lens 160, the liquid focus lens 160 being disposed between the objective lens 410 and the primary relay lens group 420 for adjusting the relay imaging focal plane of the primary relay lens group 420. Specifically, in order to realize rapid electric focusing, the liquid focusing lens 160 is further added in the infinity relay imaging subsystem 40, the first imaging information enters the infinity relay imaging subsystem 40 to perform relay imaging, the imaging light firstly passes through the liquid focusing lens 160, the liquid focusing lens 160 changes the focal length by changing the curvature of the liquid with the liquid as a lens, the liquid focusing lens 160 which is mature at present can change the shape of a liquid drop through an external voltage, thereby achieving the purpose of changing the focal length, and most of the liquid focusing lens can realize automatic focusing and zooming at present.
The maximum beam aperture angle in the infinity relay imaging subsystem 40 is about 4.2 deg., with little effect on the optical characteristics of the elements. The system has stronger expansibility, and can be compatible with filter elements with larger volume and higher requirement on an incidence angle, such as a Liquid Crystal Tunable Filter (LCTF) and the like. The minimum working distance of the infinity relay imaging system is 70mm and can be adapted to 1/2 inches and less of imaging element. The combination of the liquid lens 160 can realize rapid electric focusing and has good imaging quality in the whole working range.
In some embodiments, as shown in fig. 1, light splitting assembly 430 includes: the multi-path beam splitting lens group is arranged between the primary relay lens group 420 and the secondary relay lens group 440, is arranged at a preset angle, and is used for splitting detection light beams into multiple paths to be transmitted to different secondary relay lens groups; the filter 480 is disposed between the secondary relay lens group and the multi-path beam splitter lens group for filtering out stray light.
Specifically, light splitting assembly 430 includes dichroic mirror 490 and laser filter 480, and the formation of image light through light splitting assembly 430 is divided into two the two ways by dichroic mirror 490, and wherein the formation of image light of one way gets into vice relay mirror group 440, owing to be provided with laser filter 480 before vice relay mirror group 440, therefore laser filter 480 can filter unnecessary formation of image light, comes the collection relay imaging information through image sensor 460 to acquire laser speckle data. And the other path of imaging light enters the image sensor 470, and then the imaging light reaches the secondary relay lens group 450 to realize relay imaging.
In summary, the large field-of-view multi-modality imaging system 20, in accordance with an embodiment of the present invention, by adding an infinity relay imaging subsystem 40, a primary relay lens group 420 and a plurality of secondary relay lens groups are arranged between the objective lens 410 and the image sensor, the back working distance can be increased, the light splitting component can be conveniently inserted, the system can be conveniently expanded, the laser beam carrying speckle signals and the LED beam carrying reflected light intensity signals can be obtained through the image sensor, the data processing subsystem calculates the blood flow speed of the area to be measured according to the speckle signals received by the image sensor, and calculating the concentration of hemoglobin according to the received reflected light intensity signal, and obtaining the relative oxygen metabolic rate according to the registration calculation of the obtained blood flow velocity and the hemoglobin concentration, so that the detection of the blood flow velocity, the hemoglobin concentration and the relative oxygen metabolic rate is realized, and the real-time large-field multi-modal tissue hemodynamic parameter monitoring is facilitated. In some embodiments, the image sensor 460 used by the large field of view multimodal imaging system 20 to capture the speed of laser light carrying speckle signals is a monochrome camera, for example, a monochrome camera CCD1 can be used to receive near-infrared laser speckle signals and calculate blood flow speed.
Further, in some embodiments, the data processing subsystem calculates the blood flow velocity of the region to be measured by using a laser speckle contrast imaging method, and a mathematical formula of the contrast K and the blood flow velocity v is as follows:
wherein, taucIs the electric field decorrelation time, T is the exposure time, beta is a quantity related to the detector size, the speckle size and the polarization, v is the blood flow velocity, and the relationship between the velocity v and the contrast K can be approximately expressed as v ^ 1/K2；
The contrast K is calculated through a spatial sliding window:
In some embodiments, the LED beams include red and green beams, the image sensor for collecting the LED beams carrying the reflected light intensity signal is a color camera, the image sensor 470 is a color camera, such as CCD2, for receiving the reflected light intensity signal and calculating hemoglobin concentration of the region to be measured, and each collection of CCD1 and CCD2 is synchronized, and the collected images are registered. The imaging system field angle is approximately 52.
Specifically, as shown in fig. 4, a schematic diagram of a basic flow of data processing performed by the data processing subsystem is shown, an RGB camera is used in cooperation with a multicolor LED to perform blood oxygen imaging, and a laser speckle technique is used to perform blood flow imaging, so as to simultaneously measure a relative blood flow, an oxygenated hemoglobin concentration, a deoxygenated hemoglobin concentration, a total hemoglobin concentration, and a relative oxygenated metabolic rate.
According to the Lambert beer law, the extinction ratio and the hemoglobin concentration difference between the 0 moment and the t moment are in a relation:
log(R0/Rt)＝(εHbO(λ)ΔcHbO+εHbR(λ)ΔcHbR)Da(λ)；
wherein R is0,RtTissue reflection light intensity at 0 moment and t moment respectively; epsilonHbO(λ),εHbR(λ) are the molar extinction coefficients of HbO and HbR, respectively, at a wavelength λ; Δ cHbOAnd Δ cHbRIs the concentration difference between the time t and the time 0; da(λ) is a differential path factor, which can be obtained by monte carlo simulations in conjunction with the optical properties of biological tissue. The data processing subsystem collects the reflected light intensity signal V in the red channel or the blue channel of the color camera, substitutes the reflected light intensity signal V into the following formula, and calculates r (lambda) and L (lambda): v ═ m ═ R (λ) L (λ) d λ. Wherein R (lambda) is the spectral response of the channel, R (lambda) is the tissue reflected light intensity, L (lambda) is the light source spectral distribution, and m is the proportionality coefficient; the integration was performed in the 400-650nm range, taking into account the spectral distribution of the light source and the starting wavelength of the dichroic mirror. Therefore, the calculation formula of hemoglobin concentration based on the RGB camera can be approximately expressed as:
cHbT＝cHbO+cHbR；
wherein, VB,0,VB,tThe reflected light intensity signals V and V measured by the blue channel at the time 0 and the time t respectivelyR,0,VR,tRespectively at time 0 andreflected light intensity signal, epsilon, measured by red channel at time tHbO(λ),εHbR(λ) are the molar extinction coefficients of the oxygenated and deoxygenated hemoglobin concentrations, respectively, at a wavelength λ; Δ cHbOIs the difference in oxygenated hemoglobin concentration between time t and time 0, Δ cHbRIs the difference in the concentration of deoxygenated hemoglobin between time t and time 0; da(λ) is the differential path factor, mB,mRThe proportionality coefficients for the blue and red channels, respectively, can be calculated from the baseline conditions in combination with Lambert beer's lawB(λ),rR(λ) is the spectral response of the blue and red channels, respectively; l isg(λ),Lr(lambda) spectral distributions of the green and red beams, CHbTAs total hemoglobin concentration, CHbOIs the concentration of oxygenated hemoglobin, CHbRIs the deoxyhemoglobin concentration. Wherein the baseline of HbO concentration was set at 60uM and the baseline of HbR concentration was set at 40 uM.
To verify the effectiveness of the infinity relay imaging subsystem 40 and the multi-modality imaging system 20, experiments are required to test the effectiveness of the system. For example: the effectiveness of the system was tested using a yeast-fat emulsion mimetic experiment, first, a Hemoglobin Titration experiment (Hemoglobin Titration) was performed. 0.5mL of pig blood was added as an active substance to 80mL of phosphate buffer solution, at which time the hemoglobin concentration was about 14.2uM [30 ]. Then 2mL of 20% fat emulsion solution (final concentration 0.5%) was added as scattering agent. 0.8g yeast was added for oxygen consumption. The replica was then placed on a Magnetic stirrer (Magnetic stirrer) and mixed well. A peristaltic pump (BT100-2J LongerPump) pumps the phantom cyclically into an acrylic tube placed over the light absorbing material. Each 0.1mL drop of pig blood was added to the mimetibody to change the blood volume (increase in concentration of about 2.84 uM).
Then, an experiment of change in the oxygen content of the phantom was performed. Mock preparation was similar to before, except that swine blood was increased to 2 mL. The phantom was allowed to stand for 10 minutes before the experiment was started. We aerated the solution to change the blood oxygen content, which lasts 8 minutes. After that, the aeration was stopped and the image was taken for 8 minutes.
As shown in fig. 5, fig. 5 shows the results of the yeast-fat emulsion experiment, and (a) in fig. 5 shows the results of the Hemoglobin drop experiment (Hemoglobin Titration). The system response is approximately linear and the measured hemoglobin concentration has a good agreement with the actual hemoglobin concentration. FIG. 5 (b) shows the results of the mock oxygen content change experiment. After the air was introduced, the HbO concentration increased and the HbR concentration decreased, and then the concentration reached equilibrium. After the aeration was stopped, HbO decreased slowly and HbR concentration increased slowly due to the oxygen consumption of yeast. The HbT (total hemoglobin concentration) concentration remains constant throughout the process. This set of experimental results indicates that the system measurements are valid.
Further, to verify the effectiveness of the infinity relay imaging subsystem 40 and the multi-modality imaging system 20, an arterial occlusion experiment can be performed, wherein an adult healthy subject is selected to be tested and a six-minute cuff compression forearm ischemia experiment is performed. A cuff was attached to the upper arm of the subject, and after two minutes of rest, pressure was applied to 220mmHg for two minutes, followed by two minutes of rest. The system continuously shoots the tested hand, and the sampling speed is 1 fps. We reconstructed rBF (relative blood flow), HbO, HbR, HbT, rMRO2 (central metabolic rate for oxygen) two-dimensional maps. And a region of interest (ROI) is taken to analyze Time-series data.
Please refer to 4 healthy people aged 24-26 years as the test subjects. The subject places the hand in the imaging area and holds it still. We extract the signal of the area of the finger nail cover of the right hand being tested. Each shot lasts 40s and the sampling rate is 50 fps. We averaged the obtained blood flow values and hemoglobin concentration values within a ROI and performed time series analysis and filtered the signal with a 0.8-6Hz Butterworth band-pass filter.
As shown in fig. 6, fig. 6 shows the results of the cuff-pressurization forearm experiment. Fig. 6 (a) is a two-dimensional graph showing relative changes of rBF, HbO, HbR, HbT, and rMRO2 at different times, fig. 6 (b) is a graph showing changes of rBF, HbO, HbR, and HbT with time in the ROI region, and fig. 6 (c) is a graph showing changes of rMRO2 with time in the ROI region. After pressurization, blood flow is rapidly blocked, rMRO2 rapidly decreases, HbR continues to increase, HbO continues to decrease, and HbT slightly increases. After pressure release, blood flow and rMRO2 rise rapidly and then gradually fall back to baseline. HbO, HbR quickly fell to baseline. The sudden increase in HbT of about 10% falls back to the baseline value. And the profiles of the rMRO2 and rBF curves are relatively similar.
Fig. 7 shows the results of 4 PBV (Pulse volume change) and SPG (Speckle volume description signal) monitoring experiments tested. Fig. 7 (e) shows the local picture and ROI acquired by the system. Fig. 6 (a) is a waveform diagram of the SPG signal and the PBV signal in 10s, and both the SPG signal and the PBV signal fluctuate with the heartbeat cycle. We plot the signal amplification for one cycle, as in (b) of fig. 7. The PBV signal has a time delay compared to the SPG signal. We take the time difference between the signal peaks to calculate the time delay. We counted the histogram distribution of time delays within 40s for a single test, and as a result, the time delays of this test were concentrated in 40-100s, as shown in (c) of fig. 7. In the figure, (d) is the statistics of the mean time delay of 4 tested subjects, the mean is distributed in 57-137ms, and the mean time delay of 4 tested subjects is about 90 ms.
The above phantom experiment verifies the validity of the system measurement results. In a hemoglobin dripping experiment, the measured hemoglobin concentration keeps good linear response within a certain concentration range; however, as the concentration of hemoglobin in the solution increases, the measured hemoglobin concentration tends to be lower. This is because as the concentration of hemoglobin in the solution increases, the absorption coefficient of the solution changes, but the differential path factor used in the calculation is modeled as the initial concentration. Adjusting the monte carlo simulation parameters in time based on the measured hemoglobin concentration may solve this problem.
The speed and sensitivity of the system are verified by PBV and SPG monitoring experiments. The pulsatility of the PBV signal is due to changes in the concentration of the absorbing bolus caused by vasoconstriction and dilation, whereas the pulsatility of the SPG signal is due to changes in the dynamic scattering factor associated with blood flow. The SPG changes precede the PBV changes, probably because the blood flow velocity changes precede the dilation and contraction of the vessels. In previous studies, it has been reported that SPG signals have higher signal-to-noise ratio and robustness compared to pulse volume changes, where robustness refers to maintaining some of their performance under changes in system parameters. But the SPG signal appears to be more chaotic in this study. Since LSCI (Laser speckle signal) is very sensitive to motion information, it may be caused by motion artifact. Clinical applications also cannot ignore the effects of motion artifacts. There are some studies on the speckle image motion artifact removal, and further improvements can be made based on these studies.
In summary, according to the effectiveness of the yeast-fat milk phantom experiment and the artery occlusion experiment, it is demonstrated that the multi-modality imaging system 20 can be used in cooperation with the infinity relay imaging subsystem 40 to accurately measure the changes of blood flow and blood oxygen. The multi-modality imaging system 20 is used to monitor the body pulse total hemoglobin variation and speckle plethysmography Signal (SPG), which are indicative of body pulse blood volume variation (PBV) and pulse blood flow variation, respectively. The results show that there is a time delay of about 90ms between the SPG signal and the PBV signal.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example," or "some examples" or the like mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims (9)
1. A large field of view multi-modality imaging system, comprising:
the illumination subsystem is used for providing a laser beam and an LED beam and coupling the laser beam and the LED beam into a detection beam, and the detection beam irradiates an area to be detected of a sample to generate a speckle signal and a reflected light intensity signal;
the infinity relay imaging subsystem sequentially comprises an objective lens, a main relay lens group, a light splitting component, a plurality of auxiliary relay lens groups and image sensors which are respectively arranged corresponding to each auxiliary relay lens group;
the primary relay lens group collects detection light beams carrying speckle signals and reflected light intensity signals through the objective lens;
the detection light beam is split into a laser light beam carrying speckle signals and an LED light beam carrying reflected light intensity signals after passing through the light splitting assembly, and the laser light beam carrying the speckle signals and the LED light beam carrying the reflected light intensity signals are received by corresponding image sensors after passing through different secondary relay lens groups respectively;
the data processing subsystem is used for calculating the blood flow velocity of the region to be measured according to the speckle signal received by the image sensor, calculating the hemoglobin concentration of the region to be measured according to the reflected light intensity signal received by the image sensor, and registering and calculating the relative oxygen metabolic rate according to the obtained blood flow velocity and the hemoglobin concentration, wherein,
according to the Lambert beer law, the extinction ratio and the hemoglobin concentration difference between the 0 moment and the t moment are in a relation:
log(R0/Rt)＝(εHbO(λ)ΔcHbO+εHbR(λ)ΔcHbR)Da(λ)；
wherein R is0,RtTissue reflection light intensity at 0 moment and t moment respectively; epsilonHbO(λ),εHbR(λ) are the molar extinction coefficients of HbO and HbR, respectively, at a wavelength λ; Δ cHbOAnd Δ cHbRThe concentration difference of the hemoglobin at the time t and the time 0; da(λ) is a differential path factor, obtainable by monte carlo simulation in combination with the optical properties of biological tissue;
the data processing subsystem collects a reflected light intensity signal V in a red channel or a blue channel of the color camera, substitutes the reflected light intensity signal V into the following formula, and calculates r (lambda) and L (lambda): v ═ m ═ R (λ) L (λ) d λ;
wherein R (lambda) is channel spectral response, R (lambda) is tissue reflection light intensity, L (lambda) is light source spectral distribution, and m is a proportionality coefficient;
and calculating the hemoglobin concentration by the following formula:
cHbT＝cHbO+cHbR；
wherein, VB,0,VB,tThe reflected light intensity signals V measured by the blue channel at the time 0 and the time t respectivelyR,0,VR,tThe reflected light intensity signals epsilon measured by the red channels at the time 0 and the time t respectivelyHbO(λ),εHbR(λ) are the molar extinction coefficients of the oxygenated and deoxygenated hemoglobin concentrations, respectively, at a wavelength λ; Δ cHbOIs the difference in oxygenated hemoglobin concentration between time t and time 0, Δ cHbRIs the difference in the concentration of deoxygenated hemoglobin between time t and time 0; da(λ) is the differential path factor, mB,mRThe proportionality coefficients for the blue and red channels, respectively, can be calculated from the baseline conditions in combination with Lambert beer's lawB(λ),rR(λ) is the spectral response of the blue and red channels, respectively; l isg(λ),Lr(lambda) spectral distributions of the green and red beams, CHbTAs total hemoglobin concentration, CHbOIs the concentration of oxygenated hemoglobin, CHbRIs the deoxyhemoglobin concentration.
2. The large-field-of-view multimodal imaging system according to claim 1, wherein the image sensor for capturing the speed of laser light carrying the speckle signal is a monochrome camera.
3. The large-field-of-view multi-modal imaging system according to claim 2, wherein the data processing subsystem calculates the blood flow velocity of the region to be measured by using a laser speckle contrast imaging method, and the mathematical formula of the contrast K and the blood flow velocity v is as follows:
wherein, taucIs the electric field decorrelation time, T is the exposure time, beta is a quantity related to the detector size, the speckle size and the polarization, v is the blood flow velocity, and the relationship between the velocity v and the contrast K can be approximately expressed as v ^ 1/K2；
The contrast K is calculated through a spatial sliding window:
4. The large field of view multi-modality imaging system of claim 3, wherein the LED beams include red and green beams, and the image sensor for collecting the LED beams carrying the reflected light intensity signals is a color camera.
5. The large field-of-view multimodal imaging system according to claim 1, wherein the baseline of oxygenated hemoglobin concentration is set at 60Um and the baseline of deoxygenated hemoglobin concentration is set at 40 Um.
6. The large field of view multimodal imaging system of claim 5, wherein the data processing subsystem calculates the relative oxygen metabolism rate by the formula:
wherein, rMRO2Is the relative oxygen metabolic rate, gammaR,γTFor the vessel weighting factor, set to 1, v for simplified calculationBF,0Blood flow velocity at time 0,. DELTA.vBFIs the amount of change in blood flow velocity from 0 to t, cHbR,0Is the deoxyhemoglobin concentration, Δ c, at time 0HbRIs the amount of change in the deoxyhemoglobin concentration from time 0 to time t, cHbT,0Is the total hemoglobin concentration, Δ c, at time 0HbTThe amount of change in the total hemoglobin concentration from time 0 to time t.
7. The large field-of-view multimodal imaging system of claim 1, wherein the illumination subsystem comprises:
a laser light source for providing the laser beam;
an LED light source for providing the LED light beam;
a dichroic mirror for coupling the laser beam and the LED beam into a detection beam;
and the beam expander is arranged on the light emergent path of the dichroic mirror and used for increasing the irradiation area of the detection light beams.
8. The large field-of-view multi-modality imaging system of claim 1, further comprising a liquid focus lens disposed between the objective lens and the primary relay lens set for adjusting a relay imaging focal plane of the primary relay lens set.
9. The large field-of-view multimodal imaging system of claim 1, wherein the spectroscopy assembly comprises:
the multi-path light splitting lens group is arranged between the main relay lens group and the auxiliary relay lens group, is arranged at a preset angle, and is used for splitting the detection light beams into multiple paths to be transmitted to different auxiliary relay lens groups;
and the filter is arranged between the auxiliary relay lens group and the multi-path light splitting lens group and used for filtering stray light.
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Application publication date: 20200410 Assignee: Xinjingjie (Xiangtan) Medical Technology Co.,Ltd. Assignor: HUST-SUZHOU INSTITUTE FOR BRAINSMATICS Contract record no.: X2023980041687 Denomination of invention: Large Field of View Multimodal Imaging System Granted publication date: 20220422 License type: Exclusive License Record date: 20230914 |