Quantitative 3D Whole Breast Imaging with
Transmission and Reflection Ultrasound
Michael Andre, PhD, James Wiskin, PhD, Haydee Ojeda
Ojeda-Fournier, MD, Linda Olson, MD, David Borup
Borup,, PhD, Melissa
Ledgerwood,, B.S., Steven Johnson, PhD, many others
Ledgerwood
University of California, San Diego
Techniscan Medical Systems, Inc.
• Opportunity for Whole Breast Ultrasound
• Current scanner design
• Patient findings to date
Present Status of Breast Ultrasound
Potential Advantages of Whole Breast USCT
• Primary adjunctive modality for diagnostic imaging including
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Ultrasound Computed Tomography (USCT)
biopsy guidance but difficult to perform
Often limited to clinically assessing solid vs. cystic masses
Reader variability
Small field of view and range with high-resolution transducers
Lacks global view of entire breast
Operator dependent
Sometimes difficult to reproduce
ACRIN 6666: valuable for
screening dense breasts, difficult to do
Some states now require reporting of
fat/gland ratios as risk factor
• Global views of both breasts in
standard frame of reference
• Image is quantitative (c, α, R)
• Operator independent,
standardized scan
• Whole breast volumetric imaging
• No image speckle
• Uniform high resolution
independent of range and location
• Minimal refraction, distortion,
multiple scattering effects
• Facilitates review, follow-up
• Monitor chemo-prevention, therapy
• Guidance and correction for HIFU
Reflection
US Computed Tomography
INPUT: Known
OUTPUT: Measured
INTERACTION MAP: Desired
Ultrasound Computed Tomography:
Inherently NonNon-Linear 3D Problem
Inherently a non-linear 3D problem in
ultrasound
B-mode US is a form of limited Computed Tomography but assumes
180° backscatter, straight-line propagation, constant sound speed, etc.
Unlike x-ray CT or MRI, in US the object size ~wavelength, multiple
scattering, refraction, etc., so common 2D CT reconstruction methods are
inadequate
We implement a 3D solution to the inversion
We use non-linear full-wave 3D inverse scattering algorithm
TechniScan Medical Systems, Inc., Salt Lake City
Johnson, Wiskin
Wiskin,, Borup
Borup,, et al.
Current Whole-Breast USCT Scanner
Three Reflection Transducers angled upward at 12°, 5 MHz (80% BW)
Recently added a vertically oriented array to better access chest wall
Coincident with 2D Transmission Arrays (1536 elements) 0.5-2 MHz
All data used simultaneously in 3D non-linear full-wave inversion
Forward and back-propagation, 4-5 iterations (~45x1012 operations!)
Scan time: 10-20 sec per slice, ~ 8 min for average breast
3D Reconstruction of c, α, R in 10-12 minutes using 2 GPUs
Resolution: 0.5 mm Reflection, 0.9 mm Transmission
Sound Speed Sensitivity: 1325-1700 m/s, Detection: 7.5 m/s; Atten: 0-4 dB/cm/MHz
• Inversion is an iterative procedure
for discrete ω
ψ φsc (r,θ ) ≡ ψ φ (r,θ ) −ψ φinc (r,θ ) = ∫ K (r′,θ ′)ψ φ (r′,θ ′) g ( r − r′,θ − θ ′ )r′dr ′dθ ′
V
• Iterative minimization of residual vector must be very efficient
• We use a Ribiere-Polak conjugate gradient-based minimization FFT
• Solve Lippmann-Schwinger for scatter potential of each point in 3D
• Approximately 5-8 iterations are needed to reach 5% residual
• Data from all levels used simultaneously in 3D inversion
(~45x1012 operations!)
• Full breast 2D reconstruction in seconds, full-wave 3D is ~12 min using
very fast algorithm and GPUs
• Images of sound speed and attenuation are used to correct aberration for
Reflection Tomograms
Serves as
initial estimate
at low
frequency
(600 kHz),
iterate to
higher
frequencies
“Clock views” preserved for
review by Radiologist
300
After 3 Iterations:
Speed of Sound at 1
MHz
200
100
0
0
100
200
300
400
500
x
1 mm slice,
394x394
15 min for 250 slices
Grey scale:
1350–1700 m/sec
1350–
1380--1620 m/sec at 30 °C
1380
~7.5 m/sec contrast detectability
1650
Breast Phantom
60 views, 3 transducers
(not refraction corrected)
using Sound Speed Inverse Scatter
Tomography
Improved resolution
Reduced distortion
1.5 mm slice profile
0.3 mm FWHM in plane
400
Measured Sound Speed Sensitivity
Reflection Tomography
5.5 MHz
Same Data
Refraction Corrected
500
Typically 55-8 iterations
1600
USCT (m/sec)
• Must first solve the forward problem for
ψsc
Simple Time
of Flight
Image
y
Full--Wave InverseFull
Inverse-Scatter Image Formation
y = 0.9781x + 37.613
R2 = 0.9918
1550
1500
1450
1400
1350
1350
3D
1400 1450
1500 1550
1600 1650
True Sound Speed (m/sec)
Pre-Clinical Study of
PreWhole Breast Ultrasound
• Measure range of tissue properties and masses in
patients
• Determine equivalence to breast sonography
– 172 subjects to date at UCSD (target 300 total accrual
including Mayo Clinic)
– 19 to 78 years old
– All referred for diagnostic breast sonography
(findings on mammography or physical exam)
– Study designed to assess equivalence to sonography (93%
power)
• Determine reproducibility
WBU: Subject 901901-030 Left Breast
Biopsy-Confirmed Fibroadenoma, 40 yo
WBU: Subject 901901-044 Right Breast
Right: 6 Simple Cysts, 2 reported on US
Left: 4 Simple Cysts, none reported on US
Sound
Speed
•Intermediate
SOS (1530
m/s), distinct
margins,
spherical
Attenuation
•Very low
Atten (<0.1
dB/cm/MHz)
Coronal
Reflection
Axial
Sagittal
Corrected
for c
•Anechoic,
circumscribed
spherical
WBU: Subject 901901-030 Left Breast
40 yo with biopsybiopsy-confirmed Fibroadenoma
Sound
Speed
Reflection
Patient had series of Diagnostic US for palpable mass:
3:00, 5 cm FN, 10 mm solid, hypoechoic mass, posterior
shadowing, distinct margins
WBU: 3:00 Left breast 8 x 9 x 6 mm mass. Intermediate
sound speed (1560 m/sec), intermediate attenuation
(1.6 dB/cm/MHz), hypoechoic, distinct margins
Subject 501501-185 Left Breast
70 yo with palpable finding in upperupper-inner quadrant
Sound
Speed
Coronal
WBU: Subject 501501-185 Left Breast
C-C
Sagittal
Attenuation
Mammo Left breast 14 x 14 x 19 mm spiculated high density mass anterior zone,
Mammo:
UIQ, mildly dense fibroglandular pattern.
US: 10:00 Irregular, hypoechoic, posterior shadowing, abrupt interface,
architectural distortion, 16 x 12 mm. Note angular shape.
Pathology: Biopsy confirmed invasive ductal carcinoma
WBU: Subject 501501-185 Left Breast
Reflection
Subject 901901-077 Left Breast
33 yo seen for lump or thickening
no family history of cancer
Sound Speed
Attenuation
Reflection
WBU: 10:00 Left breast 14 x 14 x 16 mm irregular
mass. Very high sound speed (1610 m/sec), high
attenuation (2.6 dB/cm/MHz), hypoechoic, same
angular shape as sonogram, architectural distortion
Mammo Heterogeneously dense, left breast 2 cm spiculated mass, malignant
Mammo:
appearing calcifications, MOQ.
US: 1:00, 2 cm from nipple, 1.9 x 1.2 cm irregular, highly suspicious,
heterogeneous, abrupt interface.
Pathology: Biopsy confirmed invasive ductal carcinoma
WBU: Subject 901901-077 Left Breast -- IDC
Sound
Speed
Coronal
C-C
WBU: Subject 901901-077 Left
Infiltrating Ductal Carcinoma
WBU
Sound Speed
1:00 Left breast, 3 cm from nipple, 2.2 x
1.1 x 1.6 cm.
High sound speed (mean 1570 m/sec),
irregular shape, hyper to water.
High attenuation (2.3 dB/cm/MHz).
RT hypoechoic, spiculated margins,
similar irregular shape as sonogram
and mammogram
Sagittal
Coronal
Reflection
Whole Breast Ultrasound Computed Tomography
901--077 IDC
901
MG
WBU: 2.21 x 1.65 x 1.82 cm
WBU
MRI: 2.1 x 1.7 x 1.8 cm
MRI
Reflection
Sonogram
MRI: 2.1 x 1.7 x 1.8 cm
MRI
Coronal
T1
MIP
(Vid)
Sound Speed
Coronal
Coronal
Fused Reflection +
Sound Speed
Coronal
T1
Reflection
WBU: 2.21 x 1.65 x 1.82 cm
WBU
Potential Value of 3D Volumetric WBU
• WBU scan before surgery
• Both have high Sound
Speed and Attenuation
Minimum Diameter
6
WBU (cm)
P-008 72 yo
yo:: Infiltrating cancer with mixed ductal and lobular features
Work in Progress
Reader Classification: WBU and Sonography
• Teaching File of 35 cases with known findings
• 47 subjects with masses visualized on sonography
– 12 cancer, 17 FA, 8 complicated cysts, 10 simple cysts
• 98% Agreement, mass present in correct location
• BI-RADS by Sonography:
– Sensitivity=100%, Specificity=46%, and Accuracy=53%
• WBU:
– Sensitivity=100%, Specificity=54%, and Accuracy=60%
• No significant difference between two modalities
3
y = 1.8692x - 0.2076
R² = 0.665
2
1
0
0.5
1
1.5
2
2.5
3
Sonography (cm)
• Specimens did not have
clear margins
Maximum Diameter
WBU (cm)
• Illustrates a potential
advantage of global view
of breast
4
0
• Two lumpectomies
• Patient returned to surgery
to remove connecting
residual tumor
5
6
5
4
3
2
1
0
y = 1.1761x - 0.3731
R² = 0.6882
0
1
2
3
4
5
Sonography (cm)
Summary
• WBU image resolution is 0.8 mm (reflection) and 1.2 mm
(transmission)
• Slice thickness and spacing is 1 mm, 3D IST algorithm improves
image quality
• 8-10 minutes scan time per breast (size dependent)
• Independent quantitative images of speed, attenuation, reflectivity
are produced (other parameters feasible)
• Potentially new information for characterizing masses
– Simple cysts: low to intermediate sound speed, low attenuation
– Solid masses: higher sound speed and attenuation
– Malignancies: highest sound and attenuation
– Also: 3D shape, margins, texture, echogenicity, posterior pattern, etc.
• 300 patients on two prototypes at UCSD and Mayo
Acknowledgements
NIH/NCI 1 R44 CA 110203110203-01A2
Avon Foundation
UCSD CTA #20060960