Scanning Acoustic Microscopy for Medical and Biological Applications

Transcription

1 anning Aousti Mirosopy for Media and Bioogia Appiations Naohiro Hozumi Toyohashi University of Tehnoogy Kazuto Kobayashi Honda Eetronis Co., Ltd. JAPAN 1 A inia need. Optia ampe tain Observe OK! 2 > 1 hour ampe Utrasoni Observe OK! 1 2 min 1

2 3 ound peed Mirosope Aousti Impedane Mirosope 4 anning ound peed Mirosopy 2

3 Basi idea. 5 Transduer Mehania san Abnorma Water Norma Gass ubstrate Tissue 1 m Visuaize sound speed and attenuation. Comparison of two types of measurement. 6 3

4 The system is simpe. 7 Deveopment of proto-type. 8 Conventiona Proposed 4

5 Waveforms. 9 Anaysis in the frequeny domain. 1 5

6 Observation of a rat ardia aograft mode. 11 Comparison with optia mirosopy. 12 Massive hyainization in the endoardia side (eft side of the figure) assified as severe aograft rejetion. 6

7 Waveforms before and after the proessing. 13 Anaysis for separated waveforms. 14 7

8 Cauation for speifi parameters. 15 ome other parameters I (at 12 MHz). 16 8

9 ome other parameters II (at 12 MHz). 17 Commeriaized system. 18 Honda Eetronis HM one minute vasuar wa with aifiation 9

10 ummary 19 Puse driven utrasoni mirosope. Quik, Preise, Easy, Compat. Prototype: 1 x 1 resoution within 9 min. Commeria type: 3 x 3 resoution within1.5 min. Rat mioadium was suessfuy observed. 2 anning Aousti Impedane Mirosopy 1

11 Additiona needs. 21 Non-sied speimen Diret probing This presentation Future? ystem setup. 22 Intensity Time (ns) Referene Target Interna bus GPIB igna A/D board Trigger tage Driver Contro Pusar-reeiver Mehania stage Transduer 11

12 Waveforms. 23 Intensity (arb. unit) Referene Target 5 1 Time (ns) 1..5 Normaized intensity. 1. Cross-power Frequeny (MHz) Time domain Frequeny domain Caibration (assuming vertia inidene). Referene o 24 Objet ubstrate Target 1 1 o

13 Cerebeum, rat. 6-1 MHz not fixed, postnata 1 to 21 days P1 P7 P14 P21 25 Aousti impedane images 1mm tained against abindin D-28k Quantitative assessment 26 Mature Moeuar ayer (ML): parae fiber Purkinje ayer (PL) Granuar ayer (IGL) White matter Corona Maturation Immature agitta Aousti Aousti Impedane[ Impedane x1 6 N/m 3 ] P7 P14 P21 IGL ML WM Postnata [ [day] days ] 13

14 27 Improvement of spatia resoution Aberration produed by the strate (on the basis of geometria-optis) 28 max Tissue ubstrate L Transduer 14

15 Propagation of beam omponent 29 This is not true if the strate is thik and its sound speed is not the same as water. Eah beam omponent forms ringike fous. Its radius depends on the inident ange. igna proessing using 3D deonvoution 3 Cauate impuse response of the aousti system Improvement of spatia resoution. Quantitative observation. 15

16 Aberration aong atera diretion 31 Transduer fim type with PVDF-TrFE foa ength (L) 3.2 mm ange of fousing(θm) 21.5deg ubstrate poystyrene.8 mm thik sound speed() 2.3 km/s 1 θ ( θ ) sin r d tanθ sinθ L L' d tanθ Aberration aong time diretion 32 Traveing distane 1 1 L osθ 4 d 2 3 osθ L L d 2 L' 2r osθ Traveing time 1 2 t 3 2 h1 2r sinθ osθ 4 16

17 The impuse response 33 Distane (μm) Latera (r) L =1.8mm L =2.1mm L =2.4mm Inident Ange (deg) 21.4 Time Deay (x2ns) Time (t) L =2.1mm L =2.4mm L =1.8mm Inident Ange (deg) 21.4 L L θ Assumed foa ange is needed beause we do not know the exat distane from the transduer to strate 3D deonvoution proessing 34 Data 2 Impuse response D FT 3D FT Intensity Time (ns) 3D IFT Compensated Gaussian fiter 22 3D FT

18 A rat erebea tissue (intensity image) 1 mm 2 µm 35 magnify Mature Moeuar ayer (ML): parae fiber Purkinje ayer (PL) Granuar ayer (IGL) White matter Corona Maturation Immature agitta Intensity images before and after proessing. before 2 µm after 2 µm 36 IGL IGL PL PL ML WM Mature Moeuar ayer (ML): parae fiber Purkinje ayer (PL) Granuar ayer (IGL) White matter Corona Maturation Immature agitta 18

19 37 Improvement of auray Beam is foused. 38 max Target ubstrate L Transduer 1 ( ) sin ( sin ) 19

20 Caibration (assuming vertia inidene). Referene o 39 Objet ubstrate Target 1 1 o 1 1 Wave propagation. 4, z Target t, z, z t, T R ubstrate, z Longitudina t Couping medium T Transversa 2

21 21 41 Refetion onstant. t t t N M N M R ) (2 os ) (2 os ),,,,, ( 2 2 ) sin ( sin 1 ) sin ( sin 1 t t t t M 2 sin sin ) ( N os os ) sin ( sin 1 Target ubstrate Couping medium t z, t t z z,,, T R T, z 42 Transmission onstant ) (2 os ) (2 os 4 ),,,,, ( ' t t t N M N T T T ) sin ( sin 1 ) sin ( sin 1 t t t t M 2 sin sin ) ( os os N Target ubstrate Couping medium t z, t t z z,,, T R T, z

22 Normaized etion intensity. ubstrate (.8 mm) Water Refetion Intensity Apparent aousti impedane of the target assuming vertia inidene. 44 max Apparent aousti impedane of the target: app 1 1 Apparent etion onstant target: (,, ) / max ( ( ( ( 2L,,,, 2,,,, max sin R erene: (,, max 2L 2 max sin R max max max max ) / ) ) ) ) ( ( ) T ' ) T ' ( ( ) d ) d 22

23 Compensation urves. 45 Apparent (MNs/m3) 3 ) Density (kg/) Referene: air Referene: water True (MNs/m3) 3 ) Ange of fousing: 22 deg Compensation Fator Referene: air Referene: water Apparent Aousti Impedane (MNs/m3) ) Measurement for saine soution Aousti Impedane (MNs/m 3 ) erene: air erene: water after ompensation water saine air NaC ontent (wt%) Measured (MNs/m3) 3 ) Referene: air Referene: water After ompensation True (MNs/m3) ) 23

24 Cerebeum tissue of a rat mm MNs/m 3 ML PL GL WM P15 fixation by formadehyde PL GL ML Effet of ompensation. 48 Ref: water Ref: air Before ompensation vertia inidene assumed After ompensation 24

25 Distribution of the aousti impedane. 49 Cumuative Probabiity (%) 1 8 (b) air (a)water Aousti Impedane (MNs/m 3 ) 3 ) Aousti impedane images before.2 mm MNs/m 3 after IGL IGL WM WM 5.2 mm MNs/m 3 ML ML PL PL Mature Moeuar ayer (ML): parae fiber Purkinje ayer (PL) Granuar ayer (IGL) White matter Corona Maturation Immature agitta 25

26 51 Observation of brain tumor mode of rat Brain tumor, rat mm (optia, not stained) (optia, stained) rat#1 Rat1orna4 6-12MHz 4pt =2.46 (P) = deg omp. 4 x 4 mm x bks 26

27 Quantitative anaysis (average) 53 4 mm 2 1 A 2 1 A B 6 Average (MNs/m 3 ) D G C E B H F I J C I 4 D E F G H J 4 mm Optia, stained A B C D E F G H I J ROI Quantitative anaysis (standard deviation) 54 4 mm A 8 CV Roughness in aousti impedane A Position 27

28 55 Ce size observation Observation system for utured es. P fim (7 m) Cutured es Transduer Couper 56 28

29 Commeriaized system by Honda Eetronis. 57 body (new type avaiabe) stage dish dish with fim inubation e Waveform and spetrum. igna intensity (arbitrary) Time (ns) Power spetrum (normaized) Frequey (MHz) ~4 MHz range was used. 29

30 Caibration by saine soution. 59 Cutured gia es, rat. 6 2 μm 1 μm Optia Aousti impedane (MNs/m 3 ) Aousti impedane Position (x2 μm) Trae aong the white arrow Cumuative probabiity (%) Aousti impedane (MNs/m 3 ) Distribution in the ROI 3

31 In situ observation after dosage Gioma DIV14, Cytohaasin B 25μg/m min 3min 6min 9min 12min 15min 18min 21min 24min 投薬後 3 分から 1 時間の間では大きな変化は確認できないですが 4 時間後には全体的に細胞の萎縮や浮いてくるような様子が見られる 31

32 Gioma DIV14, Cytohaasin B 25μg/m min after injetion. Optia Image Gioma DIV14, Cytohaasin B 25μg/m Before injetion. Aousti impedane 32

33 Gioma DIV14, Cytohaasin B 25μg/m 6 min after injetion. Aousti impedane Gioma DIV14, Cytohaasin B 25μg/m 15 min after injetion. Aousti impedane 33

34 Refetion mode and projetion mode, Gia es. A Transduer Intensity (arb.) 8-8 Couper 5A B Time (ns) Pasti fims Cutured es 1 A B B 1 μm Projetion mode, anerous iver, rat. 2 μm 5 μm 34

35 69 Commeriaized by HONDA Eetronis HONDA Eetronis 35

36 Deveopment in Honda Eetronis 1985 Burst Driven Type Utrasoni Mirosope 25 Puse Driven Type Utrasoni ound peed Mirosope 27 Puse Driven Type Utrasoni ound peed / Aousti Impedane Mirosope Digitizer Unit DP14(ACQIRI) 2 G/s amping Rate 5 MHz Bandwidth 256 k points Aquisition Memory 5 Ω and 1 MΩ Input Impedane Compete Pre and Post Triggering 2 ppm Cok Auray for Aurate Timing Measurements Very high Data Transfer Rate amping Jitter 2pse Transfer peed 22MB/se 36

37 Contro Diagram 制御 PC PC amping Data tage Contro PCB A/D Converter Reeive 受信信号 igna Reeive igna Ampifier 増幅器 Contro Command Motor Contro signa Enode igna FPGA トリガ Trigger 発生器 Generator Disp モニタ tage ay 出回路 Position 各種制御 tage Contros Miro ワンチップ Controer マイコン Transmission Trigger Position igna X-axis Motor Driver Y-axis Motor Driver Pusar Transmission 送信信号 igna Transduer X-axis Linear Motor tage Y-axis Linear Motor Linear Motor Tabe Magnet Coi Linear Way Enoder ae troke Width 25mm Bed Resoution.1μm Max peed 1.m / s Auray of Positioning.5μm Operating Temperature ~4C, 2-8%RH Enoder head 37

38 Transduers P(VDF-TrFE) 8MHｚ D=1.6 F=2. no 32MHｚ D=.5 F=.5 1mm 1mm Pusar Reeiver (2MHz - 5MHz) 1nse Pusar Reeiver 75MHz 5MHz Fa time.8 nse Band width ２０ ７５０MHｚ ２３ｄB) 38

39 ummary Aousti impedane mirosope was proposed. 2. No need to sie, stain. Non-ontat. 3. Estimation error by assuming vertia inidene is signifiant if; (1) ange of fousing is arge or (2) erene materia is far different from target. 4. The error may be ompensated. 5. Caibration by using saine soution. 6. Cerebear tissue was observed. 7. Cutured es were observed with a suffiient resoution. 78 What an we do next? 39

40 Diret probing 79 Non-sied speimen Diret probing This presentation Future? A hybrid 2D 3D mirosope 8 2D Profie of Aousti Impedane Quantitative 3D Profie by yntheti Aperture Morphoogia 4

41 A hybrid 2D 3D mirosope Thank you for your attention. 41