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1
Photonic Remote and Continuous Photonic Remote and Continuous Biomedical DiagnosticsBiomedical Diagnostics
Zeev ZalevskyZeev Zalevsky1,21,2
1Faculty of Engineering, Bar-Ilan University, Israel2SAOT, Friedrich-Alexander Universität Erlangen-Nürnberg,
Germany
2
Main collaborators: Main collaborators:
Yevgeny Beiderman1 Javier Garcia2
Vicente Mico2 Israel Margelith1
Asaf Shahmoon1
Alexander Douplik3
Dan Cojoc4
1Faculty of Engineering, Bar-Ilan University, Israel2Departamento de Óptica, Universitat de València, Spain3Ryerson University, Toronto, Canada4Trieste, Italy
3
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
4
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
5
Any visible distance
Imaging module
Invisible Laser projection
CameraSensor
Laser
Any visible distance
Imaging module
Invisible Laser projection
CameraSensor
Laser
Any visible distance
Imaging module
Invisible Laser projection
CameraSensor
Laser
Opto-Phone: Hearing with Opto-Phone: Hearing with LightLight
6
Hearing with Light:Hearing with Light: FeaturesFeatures
•The ultimate voice recognition system compatible to “hear” human speech from any point of view (even from behind).
•There is no restriction on the position of the system in regards to the position of the sound source.
•Capable of hearing heart beats and knowing physical conditions without physical contact for measuring.
Opto-Phone: Hearing with Opto-Phone: Hearing with LightLight
7
Features- cont.Features- cont.
•Works clearly in noisy surroundings and even through vacuum.
•Allows separation between plurality of speakers and sounds sources.
•Works through glass window.
•Simple and robust system (does not include interferometer in the detection phase).
Opto-Phone: Hearing with Opto-Phone: Hearing with LightLight
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LetLet’’s listens listen……from 80mfrom 80m
Heart beat pulse taken from a throat
Cell phone
Counting…1,2,3,4,5,6
Face (profile)
Counting…5,6
Back part of neck
Counting…5,6,7
All recordings were done in a very noisy constriction site at distance of more than 80m.
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-0.5
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Results: Detection of Results: Detection of occluded objects Ioccluded objects I
(a). Camouflaged object. (b). Camouflage without the object. (c). The object (upper left part) and the low resolution camouflaged scenery.
(a). (b). (c).
(d). The spectrogram of the camouflaged object with its engine turned on. (e). The spectrogram of the object with its engine turned on and without the camouflage. (f). The spectrogram of the camouflaged object without turning on its engine.
Spectrogram
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Time [sec]
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(d). (e). (f).
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Results: Detection of Results: Detection of occluded objects IIoccluded objects II
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(a). The scenario of the experiment. (b). Experimental results: upper recording is of the camouflaged subject. Lower recording is the same subject without the camouflage.
(a). (b).
11
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
12
Technological DescriptionTechnological Description
•Unique technological platform allows remote and continuous wearable monitoring of many biomedical parameters simultaneously.
•It is based upon inspection of secondary speckle pattern back reflected from skin near main blood artery, after properly adjusting the imaging optics.
•The biomedical monitoring capabilities include: heart beats, breathing, blood pulse pressure, glucose concentration, alcohol level, IOP, blood coagulation (INR), oximetry, ICP etc.
•Unique patented IP and know how.
•Part of the applications have already been commercialized.
13
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
14
Detected rat’s breathing beating at frequency around 1.87Hz.
Reflected speckle pattern.
Noise level
Measuring of breathing from Measuring of breathing from rat’s cornea reflectionsrat’s cornea reflections
15
Detected heart beating of humans at frequency of around 1.5Hz.
Subject #1 (measurement taken while subject was holding his breath)
Subject #2 (measurement taken while subject was holding his breath)
Reference noise level (detected reflection from a wall)
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X: 1.502Y: 33.65
Frequency [Hz]
Am
plit
ud
e
(Abs) Spectrum
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X: 1.522Y: 19.96
Frequency [Hz]
Am
plit
ud
e
(Abs) Spectrum
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X: 3.078Y: 11.68
Frequency [Hz]
Am
plit
ud
e
(Abs) Spectrum
Noise level
Noise level
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Reflected speckles pattern.
Measuring of heart beating from Measuring of heart beating from human’s cornea reflectionshuman’s cornea reflections
16
Measuring breathing of pigsMeasuring breathing of pigs
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Breath Breath measured
Bre
ath
s p
er m
inu
te
Experiment
Statistical breathing experiment
The non-visible
laser system
The swine's
location
40 m
Laser beam
17
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
18
Remote heart beats Remote heart beats monitoringmonitoring
Hand
CameraLaser
50 cm
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plitu
de
[p
ix]
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Am
plitu
de
[p
ix]
Temporal plot of the outcome from the system used in the clinical trials for two different participants.
The implemented optical configuration for remote measuring of heart beats and blood pulse pressure from subject’s hand
19
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
20
Temporal plot of the outcome from the system used in the clinical tests with the graphical description of the observed parameters.
Glucose level monitoringGlucose level monitoring
21
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plit
ud
e [s
amp
];
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cose
[ml/d
l/10
]
Time [min]
Glucose /10
Param.6
Stability of the system: constant glucose level in blood (denoted by blue line with triangles) and the estimated parameter 6 (denoted by magenta line with rectangles). Glucose level is given in units of 0.1[ml/dl] (representing a constant level of 100 [ml/dl), while the estimated optical values are given in pixels.
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time [minutes]
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g/d
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,
Data of subject #1: Glucose level in blood and amplitude of positive peak (parameter #1). Glucose level is denoted by blue line with triangles and the optically measured parameter is denoted by magenta line with rectangles.
Glucose level monitoringGlucose level monitoring
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Data of subject #1: Glucose level in blood and amplitude of positive peak (parameter #1). Glucose level is denoted by blue line with triangles and the optically measured parameter is denoted by magenta line with rectangles.
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Data of subject #3: Glucose level in blood and amplitude of positive peak (parameter #1). Glucose level is denoted by blue line with triangles and the optically measured parameter is denoted by magenta line with rectangles.
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Data of subject #4: Glucose level in blood and amplitude of positive peak (parameter #1). Glucose level is denoted by blue line with triangles and the optically measured parameter is denoted by magenta line with rectangles.
Glucose level monitoringGlucose level monitoring
23
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
24
Blood pulse pressure Blood pulse pressure measurementmeasurement
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Time [sec]
Am
plitu
de
[m
mH
g]
M , Corr(M , ) = 0.99507SystolicDiastolic = S-D
An example of the obtained remote blood pulse pressure measurement using the proposed device for one subject participating in the clinical test group. The reference pulse pressure is shown by the green curve (denoted as ) was obtained using manual sleeve based reference measurement device. The blue curve (denoted as M) is the measurement obtained using the proposed optical technique. The time duration of the measurement was 350sec. The sampling of the camera was performed at 300Hz. One may see that strong correlation exists between the green (reference) curve and the blue curve obtained by the developed approach.
25
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
26
The proposed experimental configuration for remote continuous monitoring of the IOP.
Remote IOP monitoringRemote IOP monitoring
Changing IOP via modifying the height of an infusion bug.
Changing IOP via applying mechanical pressure on the sclera.
27
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plit
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Data amp: 8.017 10.7025 11.2649 11.6035 9.3484 7.2619 7.2177 6.4588
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Data amp: 7.3465
Data amplitude: 8.02 10.7 11.27 11.6 9.35 7.26 7.22 6.46
Experimentally extracted readout obtained when changing the height of the infusion bag every 500 samples.
Remote IOP monitoringRemote IOP monitoring
6.872
3.54042.9932
2.145 1.76402
0123456789
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plitu
dePressure (mm/Hg)
amp/pressure (mmHg)
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3.54042.9932
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0123456789
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de
Pressure (mm/Hg)
amp/pressure (mmHg)
1501
With infusion bagWith applied pressure
Experimentally extracted readout compared to absolute reference IOP measurement obtained with Goldmann tonometer.
28
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
29
Detection of malariaDetection of malaria
An example of one out of the 20 relevant inspected parameters. Left: Healthy RBC. Right: Infected RBC.
30
Detection of malariaDetection of malaria
Separation between infected and healthy cells. Plotting the length of the vectors versus cells’ index.
31
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
32
Remote alcohol level Remote alcohol level monitoringmonitoring
Green laser
Camera(a). (b).
(a). The side (left) and top (right) view of the experimental setup. (b). Typical temporal beating signals extracted using the proposed remote optical sensing device, before (left) and after (right) the effect of alcohol obtained over the same subject.
33
Remote alcohol level Remote alcohol level monitoringmonitoring
Definition of the Ratio wid (through the ratio between the main and the secondary negative peak’s temporal positions), Main sec peak ratio (through the ratio between the main negative peak amplitude and the secondary positive peak’s amplitude), and Standard deviation of background noise (STD) parameters.
STD of background noises: long duration test with error bars representing the std values of the measured data.
34
Remote alcohol level Remote alcohol level monitoringmonitoring
Time [min]
Pul
se s
ize
[mse
c]
Time [min]
Posit
ive
pulse
size
[mse
c] (a). (b).
Time [min]
Peak
dis [
mse
c]
Time [min]
Ratio
wid
(c). (d).
Time [min]
Mai
n se
c pe
ak ra
tio
Time [min]
Std
[mse
c]
(f).(e).
Summary:
(a). Pulse size, (b). Positive pulse size, (c). Peakdis, (d). Ratio_wid, (e). Main_sec_peak ratio, (f). Std of background noises.
35
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
36
Oximetry and coagulation of Oximetry and coagulation of bloodblood
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Oximetry experiment Blood coagulation experiment
37
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
38
The edge of the fabricated micro probe having approximately 5,000 cores while each one of them is being used as light transmitting channel (each core is a single pixel in the formed image). In this image each core transmits red channel of light at wavelength of 632nm.
Multi-Functional ProbeMulti-Functional Probe
50m
Object ImageMulti core probeInput plane Output plane
U1 U2 V
F
1 2
1 1 1
U U V F
Laser (632nm) Beam Expander Mirror
Beam Splitter
Objective LensProbe Location
CameraLaser Controller
Sample Location
39
Multi-Functional Probe- Multi-Functional Probe- experimentsexperiments
5m
2m
Experimental results of images transmitted backwards by the proposed micro probe. The scanned objects are as follows; From left to right: black vertical lines, black rectangles, horizontal black lines, black lines and black rectangle appearing in the left side of the backwards transmitted image.
Experimental results of images with Fe beads having diameter of 1m imaged through an agar solution.
40
(a) Fabricated phantom. (b) shows a 3D view sketch of the phantom having two drilled channels with diameter of 400µm each. One longitudinal channel (along the x axis) while another angled channel was made making both channel crossed inside the phantom. The openings indicated as “in” and “out” enable the connection of microfluidic system. (c) shows a cross-sectional schematic view of the fabricated phantom.
(a) (b) (c)
Phantom fabricationPhantom fabrication
41
Experimental results of Fe micro particles imaged inside a drilled phantom
Imaging of a manipulated micro wire (indicated by the solid arrows) inside an hemoglobin mixture.
Experimental results with Experimental results with phantomphantom
Imaging of fluorescence protein. HEK 293 cells transfected with pEGFP-N3. Left: Top view microscope image. Right: Imaging using the microendoscope device. Scales bar of left and right image are 50 and 20 µm, respectively.
(a) Top view microscope image of the resolution target. (b) imaging of the resolution target using the microendoscope device. Inset. Zoom image of the encompass area. Scales bar of (a) and (b) are 10 µm and 20 µm, respectively.
42
Monitoring different hemoglobin concentrations inside the phantom.
Experimental results with Experimental results with phantomphantom
43
Imaging along a blood vein of a chicken wing. The solid arrows indicate the blood vein, while the dashed arrows as well as the labeling letter indicate the cascading point between the images for constructing an image with a larger field of view
In-vivo experimental resultsIn-vivo experimental results
44
Imaging of blood vessel inside the rat’s brain using the micro endoscope
In-vivo experimental resultsIn-vivo experimental results
45
In-vivo experimental resultsIn-vivo experimental results
46
Outline•“Hearing” with light – Introduction
•Biomedical monitoring:•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
47
Conclusions:• A new technology for accurate remote and continuous sensing
of movements was developed.
• The technique is based upon processing of back reflected secondary speckles statistics.
• We demonstrated remote estimation of breathing, heart beating, blood pulse pressure, alcohol and glucose concentration in the blood stream, intra-ocular pressure measurement, oximetry, coagulation of blood etc.
• To extract precise absolute value for the measured biomedical parameters periodic personalized calibration is needed every 2-3 years.
• Ultra thin and multi-functional micro endoscope for minimally invasive medical treatment and diagnostics was presented