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Automatic Automatic Volumetric Breast Volumetric Breast
Density Density Assessment in the Assessment in the
eXtensible Imaging eXtensible Imaging PlatformPlatformRachel Embree and Christina Rachel Embree and Christina
SillerySilleryDavid Channin, MD, AdvisorDavid Channin, MD, Advisor
In Cooperation with Alex In Cooperation with Alex Shnayder, Pat Mongkolwat, Ray Shnayder, Pat Mongkolwat, Ray
WuWu
OverviewOverview
IntroductionIntroduction Material and MethodsMaterial and Methods ResultsResults DiscussionDiscussion ConclusionConclusion
IntroductionIntroduction
What is Breast Density?What is Breast Density? The breast is composed of fibroglandular tissue The breast is composed of fibroglandular tissue
embedded in a background of fatty tissue. The embedded in a background of fatty tissue. The amount of fibroglandular tissue and fat varies amount of fibroglandular tissue and fat varies among women.among women.
Breast cancer arises in this fibroglandular tissue.Breast cancer arises in this fibroglandular tissue. Mammography is projection radiography of the Mammography is projection radiography of the
breast.breast. In mammograms, dense fibroglandular tissue In mammograms, dense fibroglandular tissue
attenuates more radiation than does fat.attenuates more radiation than does fat. Breast density refers to the appearance of this Breast density refers to the appearance of this
fibroglandular tissue in a mammogram [5]fibroglandular tissue in a mammogram [5]
Breast DensityBreast Density
Positively correlated with breast Positively correlated with breast cancercancer FourFour to to sixsix times greater risk of breast times greater risk of breast
cancer for women with greater than cancer for women with greater than 60% dense tissue [1]60% dense tissue [1]
Breast density as a risk factor accounts Breast density as a risk factor accounts for as many as 30% of breast cancer for as many as 30% of breast cancer cases [1]cases [1]
Can be changed by hormonal, Can be changed by hormonal, dietary and other interventionsdietary and other interventions
Assessment of Breast Assessment of Breast Density in MammogramsDensity in Mammograms
Subjective Visual Assessment by Subjective Visual Assessment by Radiologists (Mandatory)Radiologists (Mandatory) Score the breast on a 4-point scale in Score the breast on a 4-point scale in
the Breast Imaging-Reporting and Data the Breast Imaging-Reporting and Data System (BIRADS), based on patterns System (BIRADS), based on patterns developed by Wolfe [5]developed by Wolfe [5]
Manual Image Processing Manual Image Processing Techniques (for research)Techniques (for research) PlanimetryPlanimetry Interactive ThresholdingInteractive Thresholding
Previous ApproachesPrevious Approaches Interactive ThresholdingInteractive Thresholding
GoalGoal
Create a breast density assessment Create a breast density assessment program that is…program that is… AutomatedAutomated VolumetricVolumetric AccurateAccurate In the eXtensible Imaging Platform In the eXtensible Imaging Platform
(XIP)(XIP)
Material and Material and MethodsMethods
What is XIP?What is XIP? eXtensible Imaging PlatformeXtensible Imaging Platform
Funded by NIH, NCI Cancer Bioinformatics Grid Funded by NIH, NCI Cancer Bioinformatics Grid (caBIG) Program(caBIG) Program
A program to share data, informatics tools, technologies A program to share data, informatics tools, technologies and infrastructure between the funded Comprehensive and infrastructure between the funded Comprehensive Cancer Centers across the nationCancer Centers across the nation
Open Source, Open Standards, Open Open Source, Open Standards, Open ArchitectureArchitecture
Platform for development of medical image Platform for development of medical image processing and analysis applications for processing and analysis applications for research and clinical purposes.research and clinical purposes.
Will support the DICOM Application Hosting Will support the DICOM Application Hosting standard to facilitate transportability of XIP standard to facilitate transportability of XIP applicationsapplications
XIPBuilderXIPBuilder
Visual Programming Environment for Visual Programming Environment for developing imaging applications; based on developing imaging applications; based on OpenInventor.OpenInventor.
Contains modules (lots!) that can be Contains modules (lots!) that can be assembled to perform sophisticated tasks. assembled to perform sophisticated tasks.
IncludesIncludes vTK – The Visualization Toolkit (NIH)vTK – The Visualization Toolkit (NIH) iTK – The Insight Toolkit for Registration and iTK – The Insight Toolkit for Registration and
Segmentation (NIH)Segmentation (NIH) Extensible by creating new plug-n-play Extensible by creating new plug-n-play
modulesmodules
MammographyMammography
Algorithmic FoundationsAlgorithmic Foundations
Highnam et al 1997Highnam et al 1997 Standard Mammogram Form (SMF)Standard Mammogram Form (SMF) Volumetric approachVolumetric approach Mammograms on X-ray filmMammograms on X-ray film
Van Engeland et al 2006Van Engeland et al 2006 Improved upon SMFImproved upon SMF Full Field Digital Mammography Full Field Digital Mammography
(FFDM)(FFDM) Utilized DICOM headersUtilized DICOM headers
The ModelThe Model
[2]
VolumetricVolumetric
Based on Van Engeland’s algorithm [4]Based on Van Engeland’s algorithm [4] Tissue composition is computed at each Tissue composition is computed at each
pixel and represents a rectangular pixel and represents a rectangular cylinder of tissuecylinder of tissue
Area of the pixel is computed from Area of the pixel is computed from detector characteristics and the geometry detector characteristics and the geometry of acquisition.of acquisition.
Height of the rectangular cylinder is Height of the rectangular cylinder is computed from the compression computed from the compression thickness.thickness.
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoXIPLoadDICOMSoXIPLoadDICOM Loads …Loads …
DICOM Image Pixel DataDICOM Image Pixel Data Necessary DICOM Header InformationNecessary DICOM Header Information
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoItkBinaryThresholdImagSoItkBinaryThresholdImageFiltereFilter
Each pixel compared to threshold Each pixel compared to threshold valuevalue
Output image of 0 and 1 valuesOutput image of 0 and 1 values
Input Output
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoItkMultiplyImageFilterSoItkMultiplyImageFilter
Pixel-wise multiplication of two Pixel-wise multiplication of two imagesimages
Lays background mask on top of Lays background mask on top of original imageoriginal image
Input 1 Input 2 Output
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoXIPLinearAttenuationCoeSoXIPLinearAttenuationCoefficientsfficients
Determines difference between Determines difference between effective attenuation of dense tissue effective attenuation of dense tissue and fatand fat
This Attenuation Difference This Attenuation Difference Coefficient is chosen from a table [4]Coefficient is chosen from a table [4] Based on DICOM header informationBased on DICOM header information
Anode target materialAnode target material Filter materialFilter material kVpkVp Breast ThicknessBreast Thickness
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
hhdd(r) : height of dense tissue at pixel (r) : height of dense tissue at pixel rr µµdd, eff, eff - - µµff, eff, eff : : Attenuation Difference CoefficientAttenuation Difference Coefficient
g(r) : current pixel valueg(r) : current pixel value ggff : fatty tissue reference value : fatty tissue reference value
SoXIPBreastDenseTissueSoXIPBreastDenseTissueVolumeCalculationVolumeCalculation
[4]
hhdd(r)(r) : height of dense tissue at pixel : height of dense tissue at pixel rr µµdd, eff, eff - - µµff, eff, eff : : Attenuation Difference CoefficientAttenuation Difference Coefficient
g(r) : current pixel valueg(r) : current pixel value ggff : fatty tissue reference value : fatty tissue reference value
SoXIPBreastDenseTissueSoXIPBreastDenseTissueVolumeCalculationVolumeCalculation
[4]
hhdd(r) : height of dense tissue at pixel (r) : height of dense tissue at pixel rr µµdd, eff, eff - - µµff, eff, eff : : Attenuation Difference CoefficientAttenuation Difference Coefficient
g(r) : current pixel valueg(r) : current pixel value ggff : fatty tissue reference value : fatty tissue reference value
SoXIPBreastDenseTissueSoXIPBreastDenseTissueVolumeCalculationVolumeCalculation
[4]
hhdd(r) : height of dense tissue at pixel (r) : height of dense tissue at pixel rr µµdd, eff, eff - - µµff, eff, eff : : Attenuation Difference CoefficientAttenuation Difference Coefficient
g(r)g(r) : current pixel value : current pixel value ggff : fatty tissue reference value : fatty tissue reference value
SoXIPBreastDenseTissueSoXIPBreastDenseTissueVolumeCalculationVolumeCalculation
[4]
hhdd(r) : height of dense tissue at pixel (r) : height of dense tissue at pixel rr µµdd, eff, eff - - µµff, eff, eff : : Attenuation Difference CoefficientAttenuation Difference Coefficient
g(r) : current pixel valueg(r) : current pixel value ggff : fatty tissue reference value : fatty tissue reference value
SoXIPBreastDenseTissueSoXIPBreastDenseTissueVolumeCalculationVolumeCalculation
[4]
Where does fatty tissue Where does fatty tissue reference value, greference value, gf f , come , come
from?from? Maximum pixel value (minimum Maximum pixel value (minimum
attentuation) in the interior of the breast attentuation) in the interior of the breast (this should represent a pure fat pixel).(this should represent a pure fat pixel).
Calculate a histogram of the image.Calculate a histogram of the image. Select the pixel value at 80% (empirical Select the pixel value at 80% (empirical
determination) of the maximum pixel determination) of the maximum pixel values (avoids skin edges; low values (avoids skin edges; low attenuation due to incomplete attenuation due to incomplete thickness).thickness).
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoItkBinaryThresholdImagSoItkBinaryThresholdImageFiltereFilter
Adjust parameters to detect breast Adjust parameters to detect breast edge instead of entire regionedge instead of entire region
Input Output
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
h(r) : total height of tissue at pixel h(r) : total height of tissue at pixel rr HH : compressed breast thickness : compressed breast thickness d(r) : Euclidean distance to the edge d(r) : Euclidean distance to the edge
between between breast tissue and breast tissue and backgroundbackground
[4]
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
h(r)h(r) : total height of tissue at pixel : total height of tissue at pixel rr HH : compressed breast thickness : compressed breast thickness d(r) : Euclidean distance to the edge d(r) : Euclidean distance to the edge
between between breast tissue and breast tissue and backgroundbackground
[4]
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
h(r) : total height of tissue at pixel h(r) : total height of tissue at pixel rr HH : compressed breast thickness : compressed breast thickness d(r) : Euclidean distance to the edge d(r) : Euclidean distance to the edge
between between breast tissue and breast tissue and backgroundbackground
[4]
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
h(r) : total height of tissue at pixel h(r) : total height of tissue at pixel rr HH : compressed breast thickness : compressed breast thickness d(r)d(r) : Euclidean distance to the edge : Euclidean distance to the edge
between between breast tissue and breast tissue and backgroundbackground
[4]
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
If Euclidean distance is less than If Euclidean distance is less than half of breast compression …half of breast compression … use first formula in calculation of total use first formula in calculation of total
tissue volumetissue volume
[4]
SoXIPBreastTotalTissueSoXIPBreastTotalTissueVolumeCalculationVolumeCalculation
If Euclidean distance is greater than If Euclidean distance is greater than half of breast compression… half of breast compression… use breast compression in calculation of use breast compression in calculation of
total tissue volumetotal tissue volume
[4]
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
CalculatorCalculator
Module in XIPBuilderModule in XIPBuilder
Dense Tissue VolumeDense Tissue Volume
Total Tissue Volume Total Tissue Volume x 100 = Percent Density
RADBuilder ProcessRADBuilder Process
SoXIPLoadDICOM
SoItkBinaryThresholdImageFilter
SoXIPBreastTotalTissueVolume
Calculation
SoItkMultiplyImageFilter
SoXIPBreastDense
TissueVolumeCalculation
SoXIPLinearAttenuationCoefficients
Calculator Separator
SoItkBinaryThresholdImageFilter
SeparatorSeparator
Module in RADBuilderModule in RADBuilder Displays outputDisplays output
In this case, textIn this case, text
Methods IIMethods II
20 CC full-field digital mammograms20 CC full-field digital mammograms Prior manual breast density assessment Prior manual breast density assessment
using ImageJusing ImageJ Determine breast density using Determine breast density using
Cumulus™, a popular interactive Cumulus™, a popular interactive thresholding programthresholding program
Determine breast density with the Determine breast density with the automated XIP solutionautomated XIP solution
Methods IIIMethods III
Compare the three measurements of Compare the three measurements of breast density to determine breast density to determine Kendall’s Coefficient of ConcordanceKendall’s Coefficient of Concordance
Use that coefficient to determine a Use that coefficient to determine a χχ2 2 that allows testing of the null that allows testing of the null hypothesis:hypothesis:
There is no agreement in the There is no agreement in the assessment of breast density by assessment of breast density by
the three methodsthe three methods
ResultsResults
The overall Kendall’s Coefficient The overall Kendall’s Coefficient comparing the three systems was comparing the three systems was 0.5020.502
For 20 cases and three systems, the For 20 cases and three systems, the χχ2 2 is 57.276 which allows the is 57.276 which allows the rejection of the null hypothesis (rejection of the null hypothesis (χχ2 2 of of 30.14, 19 degrees of freedom, 30.14, 19 degrees of freedom, αα =0.05).=0.05).
ConclusionConclusion
It was possible to develop, in XIP, an It was possible to develop, in XIP, an automatic software application to automatic software application to measure volumetric breast density in measure volumetric breast density in mammograms.mammograms.
The automatic measurement agreed The automatic measurement agreed well with two, independent, manual well with two, independent, manual thresholding based techniques in thresholding based techniques in common, current use.common, current use.
Future WorkFuture Work
MLO view capabilityMLO view capability Anisotropic FilterAnisotropic Filter Improve fatty reference value Improve fatty reference value
identificationidentification Validate this and other techniques Validate this and other techniques
against ground truth (MRI)against ground truth (MRI)
ReferencesReferences1.1. Boyd, N., Lockwood, G., Byng, J., Tritchler, D., Yaffe, M., Boyd, N., Lockwood, G., Byng, J., Tritchler, D., Yaffe, M.,
“Mammographic Densities and Breast Cancer Risk”. “Mammographic Densities and Breast Cancer Risk”. Cancer Epidemiology, Biomarkers & Prevention, 7, Cancer Epidemiology, Biomarkers & Prevention, 7, 1133-1133-1144.1144.
2.2. Marias K et al. “A Mammographic Image Analysis Method Marias K et al. “A Mammographic Image Analysis Method to Detect and Measure Changes in Breast Density”. to Detect and Measure Changes in Breast Density”. European Journal of RadiologyEuropean Journal of Radiology. 2004; 52:276-282.. 2004; 52:276-282.
3.3. Vacek, Pamela M., Geller, Berta M. (2004) A Prospective Vacek, Pamela M., Geller, Berta M. (2004) A Prospective Study of Breast Cancer Risk Using Routine Study of Breast Cancer Risk Using Routine Mammographic Breast Density. Mammographic Breast Density. Cancer Epidemiology, Cancer Epidemiology, Biomarkers & Prevention. 13(5). Biomarkers & Prevention. 13(5). 715-722.715-722.
4.4. Van Engeland, S., Snoeren, P.R., Huisman, H., Boetes, C., Van Engeland, S., Snoeren, P.R., Huisman, H., Boetes, C., Karssemeijer, N., (2004) A Prospective Study of Breast Karssemeijer, N., (2004) A Prospective Study of Breast Cancer Risk Using Routine Mammographic Breast Cancer Risk Using Routine Mammographic Breast Density. Density. Cancer Epidemiology, Biomarkers & Prevention. Cancer Epidemiology, Biomarkers & Prevention. 2006; 13(5):715-722.2006; 13(5):715-722.
5.5. Wolfe JN. “Risk for Breast Cancer Development Wolfe JN. “Risk for Breast Cancer Development Determined by Mammographic Parenchymal Pattern”. Determined by Mammographic Parenchymal Pattern”. Cancer.Cancer. 1976; 37:2486-92. 1976; 37:2486-92.