VisualSonics

VisualSonics
The Vevo® 770
MicroUltrasound
System
進階生物科技
產品專員 張昕淳
V1.0
Presentation Overview
• Introduction to VisualSonics Vevo system
• Understanding Ultrasound for Preclinical
Imaging
• Overview of Key Research Areas
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Cancer Imaging
Developmental Biology
Abdominal & Reproductive Imaging
Cardiovascular Research
Other Species
One Platform,
Multiple Applications
ImageGuided
Techniques
Anatomical
Functional/
Physiological
Contrast
Benefits of High-Resolution
Micro-Ultrasound
• High Spatial Resolution
Down to 30 microns
• Real-Time
• Non-Invasive
Same animal imaged longitudinally as its own
control
• High throughput screening and quantification
• Detailed anatomical, functional, physiological
and now molecular analysis
Total Small Animal Solution
• Real-time
• Longitudinal Studies
• Measure Physiological
parameters
• Contrast/Molecular
Imaging
• Translatable to man
RMV™ Scanhead , Rail &
Physiological Monitoring System
Interchangeable Mouse and
Rat Handling Platforms
Mouse Platform
Rat Platform
Anesthesia device
Optimized Workflow
 Rapid Time-to-Results
Step 1: Quick
Imaging Set-Up
Step 2: Real Time
Visualization
Step 3: Rapid
Quantification
How Ultrasound Works
Simply Ultrasound
Transducer
• Sound with
frequency > 30
MHz
• Above human
hearing
Gel
Area of
interest
Properties
Medium Speed (m/s) Acoustic impedance
(g/cm2x10^-5)
Air
330
0.0004
Amniotic
fluid
1510
1.51
Blood
1570
1.61
Bone
3500
7.8
Fat
1460
1.38
Liver
1550
1.65
Water
1480
1.48
•Ultrasound has difficulty
penetrating bone.
•Ultrasound waves do not
pass through air.
Ultrasound & Frequency
Low Frequency
Time
High Frequency
Time
Higher Frequency = High Resolution =
Lower Penetration Depth
Clinical (human)
scanners
2-13 MHz
Small animal scanners
up to 85 MHz
Comparison of Human Fetus
and Mouse Embryo in Utero
3 - 15 MHz
Conventional clinical ultrasound
(human fetus)
20cm
Cantaloupe
30 – 80 MHz
3cm
Coffee bean
Micro ultrasound
(mouse fetus)
Conventional vs. Vevo® Imaging
Cardiac – Short Axis
(14 MHz Probe)
(40 MHz Probe)
Video Loops
Conventional vs. Vevo® Imaging
Cardiac – M-mode
Septum/Anterior Wall
Left Ventricle
LV Posterior Wall
Adapted Clinical System 13MHz
Slide: Kimball, T., Cincinnati Children’s Hospital
Image*: Zhou, YQ, Mouse Imaging Centre
Dedicated Mouse System 30MHz
Conventional vs. Vevo® Imaging
Pulse Wave Doppler
Conventional vs. Vevo® Imaging
Intra-Observer Variability
Clinical
Clinical
Vevo
Vevo
Analysis courtesy of Homma, S, Columbia U., 2005
Clinical
Vevo
Study involved complete cardio phenotyping
with Vevo (30MHz) and Sequoia (13MHz) of
20 CD-1 mice (10x Normal, 10x myocardial
infarction)
Embryo through to adulthood
Embryo
Adult
Phenotypic Screening from Embryonic Stage to Adulthood
Video Loops
Vevo MicroMarker Contrast
Agents
Exclusive Partnership:
Bracco Group
Joint development and
manufacturing of MicroMarker™ kits
Video Loop
Targeted Microbubbles
MicroMarker Target-Ready
Microbubbles conjugated with antibody
Microbubble
PEG Layer
Biotin
Antibody`
Antibody
Streptavidin
Adapted from N. Ferrara & R.S. Kerbel "Angiogenesis as a therapeutic
target: advances and prospects." Nature, 438: 967-974, 2005
Cancer Imaging
Subcutaneous Tumor – Blood Flow
Regular Contrast Overlay
MIP Contrast Overlay
Cancer Imaging
Subcutaneous Tumor – VEGFR2
Isotype Control
Relative Expression of VEGFR2 in MeWo Tumor Model
Change in Contrast Amplitude
1.2
1
0.8
0.6
0.4
0.2
0
VEGFR2
VEGFR2
Isotype Control
Anteroapical Infarction in a Mouse
(Short-Axis View)
10 min delayed
Image sequence courtesy of Lindner, J.,
Oregon Health Sciences Centre, 2005
Color-coded enhancement
Cancer Research
• Screen for pre-palpable tumors
• Quantification in 2D and 3D
• Quantification in vascularity using
 Color Doppler
 Power Doppler
 Contrast Agents (MicroMarker)
• Quantification of Biomarkers (VEGFR2,
Integrins…)
Cancer Imaging
Orthotopic Tumor – B-Mode Imaging
Pre-Palpable
Tumor (60 mm3)
Earliest Palpable
Tumor (180 mm3)
*Images and histology courtesy of Dr. Marris & Nick Rhodin, Children's Hospital of Philadelphia
Quantification of Pre-Palpable
Mammary Tumors
1 mm
*WAP-TAg Mouse Model
Image courtesy of Cotarla I. and Furth, P.,
Lombardi Cancer Centre, Georgetown University
Cancer Imaging
Subcutaneous Tumor
Cancer Imaging
Subcutaneous Tumor – 3D
Volume = 115.95mm2
Paper Review:
3D Ultrasound Imaging in Preclinical
Studies of Prostate Cancer in Mice
Images: Wirtzfeld et al., Cancer Research 65: 6337-6345, 2005
Cancer Imaging
Subcutaneous Tumor – Blood Flow
Color Doppler
Power Doppler
Cancer Imaging
Subcutaneous Tumor – 3D Power
Day 1
PV = 3.18%
Image sequence courtesy of Hastie, Chambers, Lacefield and Fenster,
Robarts Research Institute, London, 2005
Day 4
PV = 11.22%
Cancer Imaging
Subcutaneous Tumor – Blood Flow
Volume = 115.72mm3, PA = 14.75%
Cancer Imaging
Subcutaneous Tumor – VEGFR2
Isotype Control
PA = 12.29%
VEGFR2
PA = 41.52%
Paper Review:
Self-destruction of Melanomas after
Pulsed Electric Fields
Day 0
Day 16
Before
After
Images: Nuccitelli et al., Biochemical and Biophysical Research Communications 343: 351-360, 2006
Poster Review (presented at AACR 2008):
Visualization and Quantification of Relative
Perfusion in 3D volume
Cancer Imaging
Transgenic Tumor – 3D
Day 0
Volume =
9.86mm3
Day 5
Volume =
13.42mm3
Tumor images courtesy of Robarts Research Institute, 2008
Cancer Imaging
Transgenic Tumor – Blood Flow
Color Doppler
Power Doppler
Volume = 7.13mm3, PV=3.13%
Tumor images courtesy of Robarts Research Institute, 2008
Cancer Imaging
Transgenic Tumor – Blood Flow
Tumor images courtesy of Robarts Research Institute, 2008
Cancer Imaging
Collagen Plug – Blood Flow
Contrast Intensity
MicroMarker Bolus Wash-in Curve for Collagen Plug
60
50
40
30
20
12
13
14
15
16
Time (Sec)
Images Courtesy of: Fortune Fry Micro-Ultrasound Core
Indiana Center for Vascular Biology and Medicine
IU School of Medicine (2007)
17
18
19
20
Cancer Imaging
Matrigel – Blood Flow
Growth Factor
Images Courtesy of: M. Tjwa, Molecular Cardiology
University of Frankfurt, 2008
No Growth Factor
Cancer Imaging
Matrigel – Blood Flow
Growth Factor
Flow
Growth Factor
No Flow
Untargeted Contrast Agent Matrigel Model
Growth Factor - Flow
Growth Factor - No Flow
No Growth Factor
No Growth Factor
Contrast Intensity
100
80
60
40
20
0
13
14
15
16
17
Time (sec)
Images Courtesy of: M. Tjwa, Molecular Cardiology
University of Frankfurt, 2008
18
19
20
Cancer Imaging
Image-Guided Needle Injection/Extraction
Cancer Imaging
Subcutaneous Tumor – Power Doppler
Image sequence, mouse model and therapeutic courtesy of Cheung A., Brown AS, Cucevic V, Roy M, Yang V,
Needles A, Hicklin DJ, Kerbel RS, Foster FS, Sunnybrook and Women’s CHSC and Imclone Systems Inc.
Developmental Biology
Embryonic Mouse
Development at E7.5
Amniotic
Cavity
1 mm
Coelomic
Cavity
Atlas of Mouse Development, MH Kaufman
Foster FS et al., Ultrasound in Med and Biol, 28:1165-1172, 2002
Ectoplacental
Cavity
Sagittal Profile at E12
Video Loop
Quantification of Embryonic
Valvular Function at E12.5
A
B
C
D
HR 280 bpm
HR 281 bpm
The ventricular septum, the dark region visible between the left and right ventricles, is forming but
incomplete . View of heart (A, B) at 12.5 days. The division of the inflow tract is visible. Yellow boxes
in (A) and (B) show sample volume locations for Doppler flow spectra from mitral orifice in (C) and
from tricuspid orifice in (D).
Images from Zhou YQ et al., Physiol Genomics 10:113-126, 2002;
Illustration from Heart Development by Harvey and Rosenthal
Injection into brain at E12
Video Loop
Profile at E17
Video Loop
Abdominal & Reproductive
Imaging
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Midline Abdominal Landmarks
Adrenal Glands
Kidney
Pancreas
Ovary
Midline Abdominal Landmarks
Video Loop
Adrenal Gland
Video Loops
Mouse Left Kidney
Video Loop
Injection into the Kidney
Video Loop
Flow within the Mouse
Pancreas
Video Loops
Ovary Imaging
Video Loops
Cardiovascular Research
Long-axis EKV® Mode
PSSA Normal vs. Infarct
Video Loops
Parasternal Long Axis View of Left
Ventricle in Adult Mouse using EKV™
Normal Heart
Image by VisualSonics
Infarct Heart
Video Loop
Scale: mm
Parasternal Short Axis
Video Loops
M-Mode Normal vs. Infarct
Infarct
Normal
Infarct Image courtesy of Kovacs, A., Washington U., 2005
Normal Image by VisualSonics, 2006
Mitral Valve Doppler
Video Loop
High Aortic Velocity and
Regurgitation
Ao
Doppler sample volume just
above the aortic valves
LV
Aortic valves
Doppler sample volume just
beneath the aortic valves
High aortic velocity over 2000mm/s
Regurgitation
Image by Yuqing Zhou, MICE
Carotid Artery
Video Loops
Adult Cardiac Injection
Plaque Build-up in Carotid
Arteries in Adult Mouse
1 mm
10 w ApoE/LDLr DKO mouse
CCA
Image sequence courtesy of Gan et al, University of Gothenburg, Sweden
40 w ApoE/LDLr DKO
mouse CCA
80 w ApoE/LDLr DKO
mouse CCA
Other Species…
Chick Embryo
Zebra Fish
Axolotl Salamander
Goby Fish
Finch Egg
Advancing preclinical research
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