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1Copyright ©2011 MicroPhotoAcoustics, Inc.
COMPANY PROFILEMicroPhotoAcoustics, Inc. (MPA)—a spin-off from Advanced Optowave Coporation—was founded in 2010 with the inventors of three-dimensional photoacoustic microscopy. Multiple patents have been licensed from Dr. Lihong Wang’s lab, Optical Imaging Laboratory at Washington University in St. Louis. MPA provides commerical photoacoustic microscopy (PAM) systems at both optical resolution (OR-PAM) and acoustic resolution (AR-PAM) worldwide.
TECHNOLOGY OVERVIEWPhotoacoustic microscopy is the fastest growing biomedical imaging technology, which affords high-resolution sensing of rich optical contrast in vivo at super-depths—depths beyond the optical transport mean free path (~1 mm in the skin). Although commercially available high-resolution three-dimensional optical imaging modalities—including confocal microscopy, two-photon microscopy and optical coherence tomography—have fundamentally impacted biomedicine, none can reach super-depths in tissue. In PAM, short-pulsed laser light is absorbed by biological tissue and converted to transient heating, which is subsequently converted into an ultrasonic wave due to thermoelastic expansion. Detection of the ultrasonic wave yields a tomographic image. Taking advantage of low ultrasonic scattering, PAM equivalently improves tissue optical transparency by a factor of 1000 and consequently enables super-depth penetration at high resolution. As a unique feature, PAM is exquisitely sensitive to optical absorption, most sensitive among all imaging modalities. PAM enables in vivo imaging of the smallest blood vessels (i.e., capillaries) and single cells with intrinsic tissue contrast (i.e., no exogenous contrast agent injected into the tissue). Both functional and molecular imaging based on optical contrast have been achieved by PAM.
PHOTOACOUSTIC MICROSCOPY SYSTEM
2Copyright ©2011 MicroPhotoAcoustics, Inc.
Comparison of Optical Microscopy Technologies
Imaging Capability Confocal Microscopy
Two-photon Microscopy
Optical Coherence
Tomography
Photoacoustic Microscopy
Depth 0.2 mm 0.5 mm 1 mm1 mm by OR-PAM3 mm by AR-PAM (50 MHz)
Contrast Fluorescence, scattering Fluorescence Scattering,
polarization Absorption
Resolution ~Depth/200 ~Depth/100 ~Depth/100 ~Depth/100
Multiscale imaging N N N Y
Sensitivity to absorption Low (6%) None Low (0.4%) High (100%)
Doppler sensing N N Y Y
Speckle artifact N N Y N
Oxygen saturation of hemoglobin N N N (poor
sensitivity) Y
Intrinsic-contrast melanin imaging N N N Y
Molecular imaging Y Y N (poor sensitivity) Y
Reporter gene imaging Y Y N Y
Imaging of metabolic rate of oxygen N N N Y
3Copyright ©2011 MicroPhotoAcoustics, Inc.
SYSTEM LAYOUT
4Copyright ©2011 MicroPhotoAcoustics, Inc.
APPLICATIONS
1) Highresolution(5μmlateralresolution)mousebrainimagingwithskullintact.
500 µm
5Copyright ©2011 MicroPhotoAcoustics, Inc.
2) Capillaryandsingleredbloodcellimaging in a mouse ear in vivo.
RBC
Capillary bed
500 µm
50 µm
6Copyright ©2011 MicroPhotoAcoustics, Inc.
0.4
sO2
1
3) Oxygenationsaturation.StructuralandfunctionalmicrovascularimagingofanudemouseearinvivobyOR-PAM.Upperleft:structuralimageacquiredat570nm;upperright:vessel-by-vesseloxygenationsaturation(sO2)mappingbasedondual-wave-lengthmeasurements.ThearteriesandveinscanbeidentifiedbasedonthesO2map.A1,arepresentativearteriole;V1,arepresentativevenule;lower:wholeearsO2map.
500 µm
100 µm
sO2
1
0
100 µm
7Copyright ©2011 MicroPhotoAcoustics, Inc.
4) Contrastagents.IntravitalPAMofamyloidplaqueswithCongoRedDye.
Fluorescence
OR-PAM
TPM100 µm
100 µm
8Copyright ©2011 MicroPhotoAcoustics, Inc.
5) Label-freePAMofocularmicrovasculatureinvivo.
200 µm
(µm)
9Copyright ©2011 MicroPhotoAcoustics, Inc.
6) Tumorangiogenesismonitoring.Longitudinalmonitoringofdoxycycline-regulatedHIF-mediatedneovascularization ina mouseear.
Non-transgenic mouse Transgenic HIF mouse
500 µm
Stage 1: D
evelopment
Stage 2: M
aintenance
d0
d1
d3
d14
d30
d60
10Copyright ©2011 MicroPhotoAcoustics, Inc.
7) Humanfingercuticle.
200 µm
500 µm
HighsO2
LowsO2
11Copyright ©2011 MicroPhotoAcoustics, Inc.
(a)
(b)
(c)
8) Transversebloodflow.Simultaneousphotoacousticimagingofoxygensaturationandbloodflow.(a)MAPofstructuralimage.(b)MAPofoxygensaturationimagemeasuredbytwowavelengths560nmand570nm.(c)BloodflowimagemeasuredbytheDopplerbandwidthbroadening.Theflowdirectionwasdeterminedbyabidirectionalmotorscanning.(d)Thevasculartraceswiththeoxygensaturation,averagedalongthesegmentsofthevessels.(e)Thevasculartraceswiththebloodflowvelocity,inmillimeterspersecond,averagedalongthesegmentsofthevessels.(f)Thetransversevelocityprofileofthebloodflowindicatedbythedashedlinein(c).Scalebar=250μm.
Min
4
2.
0
-2
-4
1.0
0.9
0.8
0.7
0.6
velo
city
(mm
/s)
Flow
vel
ocity
(mm
/s)
Oxy
gen sa
tura
tion
Opt
ical
abs
orpt
ion
(d)
(e)
(f)
6
4
2
0
-2
-4
-60 200 400 600 800 1000
Position (µm)
M
ax
12Copyright ©2011 MicroPhotoAcoustics, Inc.
9) Monitoringofmelanomagrowthonanudemouseear.(a)PAMimageofbloodveselsintheearacquiredbeforeinjectionofmelanomacells.(b)PAMimagewhereinvivoredbloodcells(RBCs)canbeidentified(theclose-upimageindicatesthebiconcavestructureofRBCs).(c)PAMimageofbloodvesselsandmelanomatakenfourdaysafterinjectingmelanomacells.ThemelanomaimageisextractedbytakingthedifferenceofthetwoPAMimages[(a)and(c)]andisplottedingray:MT,melanomatumor.(d)Opticalmicroscopyimage(0.057NA)ofthesameareain(a)and(c).
a) b)
c)
Vasculature
Melanoma
max
min
d)
200 µm 20 µm
5 µm
MT
RBC
13Copyright ©2011 MicroPhotoAcoustics, Inc.
10) Imageofsmallintestine.
25 µm
25 µm
PAM image of section without staining.Section thickness: 6 µm.
Optical micrograph (20X, 0.45 N.A.) of the section stained by hematoxylin and eosin.
14Copyright ©2011 MicroPhotoAcoustics, Inc.
OR-PAM Systems
In vivo imaging at tissue depths up to 1.2 mm
Lateral resolution down to 5 µm
Axial resolution down to 15 µm
Integrated, KHz tunable laser
AR-PAM Systems
In vivo imaging at tissue depths up to 3 mm
Axial resolution down to 15 µm
Lateral resolution down to 45 µm
Integrated, KHz tunable laser
TECHNICAL SPECIFICATIONS
15Copyright ©2011 MicroPhotoAcoustics, Inc.
MicroPhotoAcoustics Inc113 Comac Street
Ronkonkoma, NY 11779, USA
Tel : 1-631-974-6268,
Fax : 1-631-389-2554
Web : www.biompa.com
MicroPhotoAcoustics Inc. follows a policy of continuous product improvement. Specifications are subject to change without notice.
MicroPhotoAcoustics Inc offers a limited warranty for its products. For full details on warranty coverage, or for further product information,
please contact MicroPhotoAcoustics Inc.