Sound Light: photoacoustic imaging of cancer

Transcription

1 Sound Light: photoacoustic imaging of cancer Wiendelt Steenbergen MIRA institute / Biomedical Photonic Imaging Group Biomedical Photonic Imaging group

2 Geography Twente Amsterdam Enschede (55000 inhabitants) Enschede

3 Enschede 5 Photoacoustic Imaging p = Γμ a Φ ( x, y, z) Absorption Temperature rise Thermal expansion Stress Sound 6

4 Overview of tumor imaging studies Animals: Vascularisation during tumor growth Humans: PA Mammography 7 Detection geometries Wide angle detection - Reconstruction needed + Can be made into array Focussed detection + No reconstruction needed - Cannot be made into array 8 4

5 Photoacoustic imaging of subcutaneous tumor Lewis rat (male, 50 g) 8 x 0 6 pancreas tumor cells injected subcutaneously in hind limb Measurements on day, 7, 8 and 0 (tumor injected on day ) Wavelength 064 nm Pulse duration 4 ns Pulse energy mj Focussed and unfocussed detector 9 day 8 day day 7 Lewis rat (male, 50 g) Subcutaneous pancreas tumor Wavelength 064 nm Focused detector day 0 0 5

6 Maximum intensity projections 0 x (mm) unfocussed sensor y (mm) day day 7 day 8 day 0 focussed sensor Thumma et al., Optics Express (005) 6

7 Overview of tumor studies Animals: Vascularisation during tumor growth Humans: PA Mammography The Photoacoustic Mammoscope (PAM) ultrasound detection array, MHz Phys. Med. Biol. (005) ND-YAG laser, 064 nm, pulse energy 60 mj 4 7

8 panel panel panel panel 4 5 Photoacoustic mammography pilot study Inclusion criteria Palpable lump X-ray and US: high suspicion for malignancy Pre-selected by clinician for high probability of detection Subjects in good general health (45 minutes exam) Of legal age; fully competent to give informed consent etc Exclusion criteria Patients with history of surgical biopsies Manohar et al., Optics Express (007) 6 8

9 Case 57 year, Caucasian Palpable lump central in right breast Carcinoma with neuroendocrine differentiation ROI photoacoustic scan: 4x46 mm Breast thickness in scanner: 59.5 mm 7 Case (#066665) 8 9

10 Optics Express (007) MIP image top view Carcinoma Pathology: tumor size = 6 mm Photoacoustics: tumor size = 5 x mm 9 X-ray Photoacoustics Steps of ¼ mm, from 0 to 5 mm depth 0 0

11 Slices starting at 7 mm in steps of mm Slices starting at mm in steps of mm

12 Photoacoustics, current status Capabilities of PA shown in vivo for Imaging of implanted subcutaneous tumors Resolution: μm Measurement depth: 5 mm Breast imaging Instrumental resolution mm Measurement depth 5-0 mm (8 averages) Needs for better photoacoustics faster imaging Parallel signal acquisition (money) more quantitative imaging More signals for better image reconstruction Cope with acoustic tissue inhomogeneities Measure absolute concentration of substances 4

13 PAM: from flat plate to tomography 5 Needs for better photoacoustics faster imaging Parallel signal acquisition (money) more quantitative imaging More signals for better image reconstruction Cope with acoustic tissue inhomogeneities Measure absolute concentration of substances 6

14 Imaging of acoustic parameters Speed of sound and attenuation 7 PVA inclusion in an agar phantom 8 4

15 Effect of assumed speed of sound on PA image Assumed SOS=490 m/s Using measured SoS map 9 Effect of assumed speed of sound on PA image 0 5

16 Water 490 m/s % agar 494 m/s 8 mm Agar, milk, indian ink 508 m/s 0. Np/cm 5.5mm PA Image SOS Attenuation Needs for better photoacoustics faster imaging Parallel signal acquisition (money) more quantitative imaging More signals for better image reconstruction Cope with acoustic tissue inhomogeneities Measure absolute concentration of substances 6

17 Photoacoustic Imaging p = ΓμaΦ( x, y, z) Absorption Temperature rise Thermal expansion Stress Sound Tissue is a pinball machine BSc thesis H.E. van Herpt 4 7

18 The quantification problem of photoacoustics Initial pressure in absorbing volume after laser pulse: Ρ = Γμ Φ 0 a ( x, y, z)? Γ: Grueneisen coefficient Φ(x,y,z): Fluence Can we estimate absolute absorption coefficients without using a light transport model? μ a Yes 5 Principle : labeling of light acousto-optic modulation tissue light in ultrasound source photon in Δp, Δρ, Δn<0 Δp, Δρ, Δn>0 Labeled photon out 6 8

19 Step : PA excitation in point and μ a p p Φ = ΓμaΦ = fluence p μ a p = ΓμaΦ 7 Step : label the light inject in, label in, detect in p L μ a Amount of labeled light detected in : p L Pr(,,) Pr(,) Pr(,) Pr(,) Pr(,) Φ Φ 8 9

20 Step : combining measurements p p p L = Γμ Φ a = ΓμaΦ Φ Φ equations, unknowns μ = c a p p pl 9 Verification with Monte Carlo 0 mm z μ s =0.4 mm- x D slab, thickness 0 mm Single absorbing inclusion: μ a =0.05, 0.05 and 0. mm - Position variations for the absorbing inclusion: At fixed x=y=0: 4<z<6 mm 40 0

21 Ρ0 = Γμa Φ( x, y, z) Verification with Monte Carlo varying z-position #absorbed photons pressure=μ a φ 0.0 E Real μ a of inclusion (mm - ) μ a measured with Sound Light (mm - ) Sound Light μ a =real μ a Real μ a (mm - ) 4 SOUND LIGHT: PRELIMINARY EXPERIMENTAL RESULTS PA pressure P PA pressure P Abs Abs Abs Abs Abs Abs US-labeled light P L Pa a μ P = 0.09 a P La, Pa a μ P a = P La, 4

22 SOUND LIGHT IN ONCOLOGY PAM, PAM Research: quantification of neovascularisation smart contrast agents local drug delivery molecular processes Clinical: mammography screening diagnosis monitoring of therapy 4 Acknowledgments University of Twente: Srirang Manohar Sanne Vaartjes Erwin Hondebrink Johan van Hespen Jithin Jose Kiran Kumar Thumma Raja Gopal Rayavarapu Roy Kolkman Rene Kroes Heike Faber Gerbert ten Brinke Khalid Daoudi Alex Bratchenia Rob Kooyman Ton van Leeuwen External: Ronald Siphanto (Erasmus Medisch Centrum) Han van Neck (Erasmus Medisch Centrum) Joost Klaase (Medisch Spectrum Twente) Frank van den Engh (Medisch Spectrum Twente) 44