Photoacoustic Imaging of Blood Vessels in Tissue

Transcription

1 of Blood Vessels in Tissue F.F.M. de Mul (University of Twente, Enschede, the Netherlands) FdM [µm] Imaging methods for hidden structures in turbid media (tissue) OCT/ OPS (C)M TOF / FM NIR green C(M) : (confocal) microscopy OCT: optical coherence OPS: orthogonal polarization spectral imaging photoacoustics TOF: time-of-flight FM: frequencymodulated Depth [µm] Depth FdM Optical properties of tissue and blood piezodetector Pulsed laser beam Scattering and absorption (Reduced) Scattering coefficient: λ = 8 nm: tissue surface Perfused tissue blood cell acoustic shock wave Dermis: mm - Blood: λ = 8 nm: Dermis: Blood:. light pulse is absorbed in blood cell Depth: adiabatic heating Green light: - 9 mm pressure pulse emerging ( m/s) Near-infrared: mm detection at tissue surface : µm FdM Available windows: FdM 4 c p,β,v E a,τ l Photoacoustic Signal Generation r Bipolar PA-signal generated by a spherical Gaussian Source τ a = ( t τ ) t τ P( r, t) = Pmax ( r) e exp τ e τ e r τ = ν Rσ ν τ t β Ea Pmax( r) = R / σ e(π ) c pτ e r FdM e a τ = τ + τ l Hydrophone output [mv] Time [µs] erythrocytes µmsphere Diameter: µm (compared with a µm blue polystyrene sphere) detection distance:.7 mm ( =. µs x m/s) medium: water/pbs FdM - Hydrophone output [mv] Two erythrocytes

2 Gold top layer (ground) PVdF Fiber Double-Ring Detector One-fiber illumination Directional Sensitivity Housing (brass) Ground Electrodes (cylindrical) Disk-shaped Detector Ring illuminator Dielectric Housing (brass) Ground Gold top layer (ground) PVdF Fiber Electrode FdM Diam.. mm Dielectric 7 Disk Detector: FWHM : Depth : Ring Detector: FWHM : Depth : 7 FdM 8 PA signal [mv] 9 hair in water chicken breast (no hair) A human hair in chicken breast tissue. hair in chicken breast Depth: mm ( 4 µs x - Large ring det. m/s) Average 8 x FdM Time (µs) 9 mm mm Z = 4. mm mm Z =. mm Vessels in chicken breast tissue Sample : mm thick chicken breast tissue in water Image : mm, inside sample, % isosurface threshold Vessels : Nylon capillaries,.8.4 mm diameter Absorber : Evans Blue, flowing, a = cm- Detection : at Z = mm, points,. mm spacing FdM Reconstruction of hidden objects mm mm..7 Depth mm Material: carbon threads ( µm) on transparent sheets, mm in % Intralipid-% (resembles human tissue scattering).7 mm FdM : µ m FdM

3 PA-imaging of blood vessels in tissue Live Albino Wistar Rat: Epigastric artery branching Z = 7. mm 7. mm. mm Z =. mm 7. mm Photograph Depth Vascular tree from a branching epigastric artery of a rat. Ex-vivo; medium: intralipid % ( tissue). Depth (Z-coord.) mm : indicated in figure. Laser power nm, mj/pulse through fiber µm. / lateral resolution: / µm respectively. FdM 7. x 7. x 7. mm FdM 4 PA-imaging of blood vessels in tissue Albino Wistar Rat: Brain Perfusion Alive Rat Slices of µm Area: 4 mm x 4 mm Depth: mm PA-image of Vessels in Rabbit Ear Blood in the cartilage scalp, in the upper part of the occipital bone Double-ring detector. Dead Perfused Rat Area: mm x mm mm x mm Depth: mm FdM Figures are made out of scan steps in X-direction, with a step size of. mm. Y-Scan consists of 9 lines, separated. mm Signal processing: summing the data of the separate rings, FdM after correction for the time delay. mm 8 mm Y scan (mm) Double-ring detector. Figures are made out of scan steps in X-direction, with a step size of. mm. Y-Scan consists of 9 lines, separated. mm (figure -9). Signal processing: summing the data of the separate rings, after correction for the time delay. Bipolar shape: front and backside Depth 9.. (mm) X scan (mm) FdM 7 8 mm PA-image of Vessels in Rabbit Ear Depth PA-imaging of blood vessels in rabbit ear Scan Direction 7-7 Time [µs] PA signals: capillaries in % IL-% FdM 8 PA Signal ( ) [mv] x.7 mm tubing Front and backside of the vessel.7 x.94 mm tubing PA Signal ( ) [mv]

4 E-.E E-.E PA-imaging of blood vessels: image correction.e-.e+ mm diameter rubber tube, filled with human blood, in 7.% Intralipid-% dilution. Image A : D image, from measured time signals (D-depth images), plotted as lines in the D image next to each other. PA-imaging of blood vessels: image correction A: originally measured time signals.e- B: after multiplication with autocorrelation (STEP ).E A B.E-.E+ Image B : D image, after correction by multiplication with the zero-time crosscorrelation function, (C ) : STEP FdM 9 Cross correlation (normalized) [-] C C.E+ C: after fit to bipolar signal (STEP ) Upper/lower image: pos./neg. peak signal (here absolute value plotted) FdM D.E+ D: after running integration over depth (STEP ) PA-imaging of blood vessels in rabbit ear PA-imaging of blood vessels in rabbit ear: occlusion 4 Y sca n 7 8 (m m) Left: before corrections De mm 9.. Right: after corrections. pth.. - (m m) X scan 8 mm FdM (mm) Time [µs] A maxtime mintime Occlusion Occlusion Peak - peak time [µs]..4 Occlusion Occlusion During occlusion: A: Time between max / min peak reduced (. µs. mm) B: Peak-peak time delay reduced => vessel thinner C: Peak-peak amplitude reduced => amount of blood lower FdM B peak-peak value [mv] 4 C Occlusion Occlusion PA-imaging of blood vessels in rabbit ear: flushing with saline In vivo Scan: Human Blood Vessels Amplitude [mv] Time (µs) Blood in vessel Flushing with Saline Amplitude [mv] Peak - peak value Max value - Min value - - FdM FdM 4 4

5 PA-imaging of blood vessels in human arm Photoacoustic Mammography Depth - mm Stepper motor fibre x-y scanning system Transmission mode Top compartment Transparent glass plate FdM Acoustic wave PVDF film Compressed breast Tumour site Display Detector matrix Multiplexers & amplifiers Bottom compartment Data acquisition FdM system cards The detector matrix Image reconstruction algorithm.7.7 sensor array plane of detection voxel synthetically scanned volume in sample P: pressure transient F: filter δ: delay w: weight factor H: transfer function of transducer S: detector output T: time window arranged in a cartesian grid elements size: x mm separation:.7 mm element accessed at a time 9 element microphone matrix active area: 9 x 8 mm FdM 7 S δ, T, P H F w δ S, T, w P H F S n δ n T, Analysis Source P H n F w n n n Intensity FdM 8 Σ Phantom: mm, 7x sphere at depth mm 9 7 isometric view Absorption contrast Sphere : medium = 7 : side view FdM 9 Absorption coefficient [/mm] Scattering coefficient (reduced) [/mm] Absorption Contrast Penetration into tissue Applications Green nm dermis blood. Cutaneous perfusion Wound healing Diabetes Vascular malformations Skin tumours NIR 8-4 nm dermis blood... Cerebral perfusion Muscular perfusion Mammography Angiogenese FdM

6 Imaging methods for hidden structures in turbid media (tissue) [µm] OCT/ OPS (C)M TOF / FM NIR green C(M) : (confocal) microscopy OCT: optical coherence OPS: orthogonal polarization spectral imaging photoacoustics TOF: time-of-flight FM: frequencymodulated Depth [µm] Depth FdM Of Blood Vessels in Tissue The end FdM