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Expressing Medical Image Measurements using the Ontology for Biomedical InvestigationsHeiner Oberkampf1,2, James A. Overton3 Sonja Zillner1, Bernhard Bauer2 and Matthias Hammon41 Siemens AG, Corporate Technology2 University of Augsburg, Software Methodologies for Distributed Systems3 Knocean4 University Hospital Erlangen, Department of Radiology
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Agenda
1. Measurements in radiology and pathology2. Expressing measurements using OBI
1. OBI value specifications2. Size measurements3. Density measurements4. Ratio measurements
3. Normal size, density and ratio specifications4. Applications
1. Information Extraction2. Normality Classification3. Inference of Change
5. Demo
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Typical Measurements in RadiologyNot comprehensive
Sizelength (1D, 2D, 3D), area, volumeindex (e.g. spleen index = width*height*depth)
Density measured in Hounsfield scale (Hu):mainly in CT imagesminimal, maximal and mean density values for Regions of Interest (ROIs)
Anglee.g. bone configurations or fractions
Blood flowe.g. PET: myocardial blood flow and blood flow in brain
…
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Measurements in PathologyNot comprehensive
Sizelength (1D, 2D, 3D), area
Weightweight of resected tissue, nodule or tumor
Ratiosimmunohistochemical staining of tumor cells
Other measurementsviscosity of blood, serum, and plasmamitotic rateserum concentration…
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Expressing Measurements using OBI
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obi:value specificationShared structure in different contexts
The element "1.8cm" can occur in many different parts of a biomedical investigation.It might be part of:
• the data resulting from a measurement of one of John's lymph nodes, made on January 12, 2014 in Berlin
• a protocol, i.e. a specification of a plan to make some measurement• a prediction of the result a measurement planned for the future• a rule for classifying measurements• many more…
OBI uses the "value specification" approach to capture the shared structure across different usesand allow for easy comparison between them.
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obi:value specificationDefinition and relations
Definition: An information content entity that specifies a value within a classification scheme or on a quantitative scale.
Example of usage: The value of 'positive' in a classification scheme of "positive or negative"; the value of '20g' on the quantitative scale of mass.
A scalar value specification has a numeric value and a unit of measurement. We connect them together with these relations:
• obi:has value specification: connect some particular measurement datum, prediction, etc. to a value specification
• iao:has measurement unit label: determine the unit of measurement for the value specification
• obi:has specified value: determine the numeric value for the value specification
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OntologiesBesides OBI the following ontologies are used to express measurements.
OBO LibraryBasic Formal Ontology (BFO)Relations Ontology (RO)Information Artifact Ontology (IAO)Ontology for General Medical Science (OGMS)Units Ontology (UO)Phenotypic quality (PATO)Biological Spatial Ontology (BSPO)
OtherRadiological Lexicon (RadLex)Model of Clinical Information (MCI)
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Length measurementsExample: Enlarged lymph node with diameter 1.8 cm.
_:vs uo:centimeteriao:has measurement unit label
uo:length unit
“1.8”^^xsd:float
_:diam-LN
obi:has specified value
_:md
iao:length measurement datum
obi:has value specification
pato:diameter
_:ln
radlex:lymph nodeogms:clinical finding
_:cf iao:is about
ro:has_part
iao:is quality measurement of
obi:scalar value specification
bfo:inheres in
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Length measurementsExample: Transverse diameter of kidney 5.2 cm.
_:vs uo:centimeteriao:has measurement unit label
uo:length unit
“5.2”^^xsd:float
_:widthOfKidney
obi:has specified value
_:md
iao:length measurement datum
obi:has value specification
pato:width
:kidney
radlex:kidneyogms:clinical finding
_:cf iao:is about
ro:has_part
iao:is quality measurement of
obi:scalar value specification
bfo:inheres in
_:sp
bspo:sagittal plane
bspo:orthogonal_to
_:sp
bspo:left-right axis
bspo:parallel_to
owl:Class
:instanceLegend:
Note: Instances with underscore represent blank nodes
rdf:type
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2D MeasurementsExample with RECIST
RECIST(Response Evaluation Criteria In Solid Tumors)
“First you need to identify the longest [in plane] diameter of a lymph node or nodal mass (here 56.0mm) and then choose the longest perpendicular diameter to that as the short axis (here 45.3mm).”
Source: http://www.recist.com/recist-in-practice/19.html
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2D MeasurementsExample: Lymph node with diameter 56.0 x 45.3 mm.
_:longest-diam
_:md
_:ln
radlex:lymph node
_:cf iao:is about
iao:is quality measurement of
_:md2
_:diam-short-axis
obi:has value specification
mci:longest diameter
_:vsuo:centimeter
uo:length unit
“5.6”^^xsd:float
obi:scalar value specification
_:vs2 “4.53”^^xsd:float
obi:has specified value
mci:short axis
ro:has_part
iao:length measurement datum
mci:two directional size finding
bspo:orthogonal_to
ogms:clinical finding
_:tp
bspo:transverse plane
bfo:inheres_in
bspo:axis within plane
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Volume MeasurementsExample: Volume of spleen 201.136 cm³.
_:vs
uo:cubic centimeteriao:has measurement unit label
uo:volume unit
“201.136”^^xsd:float
:volume-of-spleen
obi:has specified value_:md
iao:measurement datum
obi:has value specification
pato:volume
:spleen
radlex:spleenogms:clinical finding
_:cf iao:is about
ro:has_part
iao:is quality measurement of
obi:scalar value specification
bfo:inheres in
Source: “Automatische Detektion und volumetrische Segmentierung der Milz in CT-Untersuchungen“ – M. Hammon, P. Dankerl,M. Kramer, S. Seifert,A.Tsymbal,M. J. Costa, R. Janka,M. Uder, A. Cavallaro
Segmentation algorithms used to determin the volume of organs.
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Density Measurements
Density is measured in Hounsfield unit (HU)
Density measurements given for a region of interest (ROI)
Minimal, maximal and mean values for the pixels of the ROI
Examples:“Density of a liver cyst 8 HU”
Density measurement of a liver cyst
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Density MeasurementRepresentation with obi:mean calculation
_:vsiao:has measurement unit label
radlex:Houndsfield unit
“8.0”^^xsd:float
_:density
obi:has specified value
_:md
iao:measurement datum
pato:mass density
:region of interest
ogms:clinical finding
_:cf iao:is about
iao:is quality specification of
obi:scalar value specification
_:cyst
bfo:inheres inro:has_part
radlex:cyst
obi:has value specification
_:mc
obi:mean calculation
obi:has specified output
obi:has specified input
_:av
obi:average value
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Ratio Measurements
Ki-67 immunostaining of brain tumor cellsSource: Wikipedia
Percentage of Ki-67 positive tumor cellsKi-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells. In breast cancer, a result of less than 10% is considered low, 10-20% is intermediate/borderline, and more than 20% is considered high.
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Representation of Ratio MeasurementsExample: 10 % of Ki-67 positive tumor cells
mci:prevalence of Ki-67 positive cells in a tumor
:prevOfKi67
iao:is quality specification of
:Ki-67+ cell ratio specification
pato:quality
tumor
_:tumorbfo:inheres in
obi:has value specification
uo:percent
uo:ratioobi:scalar value
specification
_:svs
“10”^^xsd:floatobi:has specified value
iao:has measurement unit label
iao:scalar measurement datum
Work-in-progress
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Representation of Ratio MeasurementsExample: 10 % of Ki-67 positive tumor cells
:number of tumor cells
tumor
:tumor
:number of Ki-67+ tumor cells
pato:quality
pato:count
_:numberOf tumor cells
bfo:inheres in
_:numerator
iao:scalar measurement datum
_:denominator
iao:is quality specification of
_:numberOfKi67+ tumor cells
obi:scalar value specification
_:svsDen
_:svsNum
obi:has value specification
uo:countiao:has measurement unit label
iao:measurement datum
Numerator and denominator should be explicit and could be represented as ‘iao:measurement data item’ or ‘iao:scalar measurment datum’ or stato:count similar to the definition in STATO. This has the advantage that dimensional and dimensionless ratios can be represented in the same form.
Work-in-progress
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Normal Specifications
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Normal Upper Bound SpecificationExample: Lymph nodes are normally up to 1 cm.
iao:information content entity
_:vsuo:centimeteriao:has measurement unit label
uo:length unit
“1.0”^^xsd:floatobi:has specified value
obi:scalar value specification:has value specification
_:ns
mci:upper bound specification
radlex:lymph node
:normalDiameterOfLymphNode
pato:diameter
bfo:inheres in
pato:normal
_:lniao:is quality specification of
pato:length
pato:size
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Normal Interval SpecificationExample: Normal diameter of the pulmonary atery is between 1.6 and 2.6 cm.
uo:centimeter
uo:length unit
“2.6”^^xsd:float
obi:scalar value specification
:has value specification_:ubsp
mci:upper bound specification
_:lbsp
mci:lower bound specification
_:vs-lower-b “1.6”^^xsd:float
_:vs-upper-b
_:isp
mci:interval specification
radlex:pulmonary atery
:normalDiameterOfPulmonaryAtery
pato:diameter
bfo:inheres in
pato:normal
_:pa
pato:length
pato:size
iao:is quality specification of
ro:has part
iao:has measurement unit label
obi:has specified value
:has value specification
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Normal Interval SpecificationExample: Normal length of kidney along craniocaudal axis: 8.0 – 13.0 cm.
uo:centimeter
uo:length unit
“13.0”^^xsd:float
obi:scalar value specification
:has value specification_:ubsp
mci:upper bound specification
_:lbsp
:mcilower bound specification
_:vs-lower-b “8.0”^^xsd:float
_:vs-upper-b
_:isp
mci:interval specification
radlex:kidney
:normalkidneylengthTP
pato:normal
_:kidney
pato:length
pato:size
iao:is quality specification of
ro:has part
iao:has measurement unit label
obi:has specified value
:has value specification
bspo:transverse plane
_:tpbspo:orthogonal_to
bfo:inheres in
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Normal Interval SpecificationExample: Normal mass density of the spleen in Hounsfield scale: 40-50 HU.
“50.0”^^xsd:float
obi:scalar value specification
:has value specification_:ubsp
mci:upper bound specification
_:lbsp
mci:lower bound specification
_:vs-lower-b “40.0”^^xsd:float
_:vs-upper-b
_:isp
mci:interval specification
radlex:spleen
:normalDensityOfSpleen
pato:mass density
bfo:inheres in
pato:normal
_:spleen
iao:is quality specification of
ro:has_part
iao:has measurement unit label
obi:has specified value
:has value specification
radlex:Houndsfield unit
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Expressing a Reference PopulationUse punning of PATO qualities
obi:population
:humans51to60years
uo:year
uo:time unit
“60”^^xsd:integer
obi:scalar value specification
:has value specification_:ubsp
mci:upper bound specification
_:lbsp _:vs-lower-b “51”^^xsd:integer
_:vs-upper-b
_:isp
mci:interval specification
pato:age
iao:is quality specification of
ro:has part
iao:has measurement unit label
obi:has specified value
:has value specification
mci:population defined by
mci:population characterised by
Populations, defined by certain qualities (e.g., age or gender) are represented by punning the respective PATO qualities.
mic:lower bound specification
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Link Normal Specifications to Reference PopulationLink to Normal Specifications
_:ubs
mci:upper bound specification
mci:defined for reference population obi:population
:humans51to60year
radlex:head of pancreas
bfo:is quality of
pato:normal
iao:is quality specification of
pato:size
:nsize _:hop_:ubs
mci:interval specification
ro:has_part
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Normal RatiosExample: Normal levels of creatinine in the blood are 0.6-1.2 mg/dL in adult males
“12.0”^^xsd:float
obi:scalar value specification
:has value specification_:ubsp
:upper bound specification
_:lbsp
:lower bound specification
_:vs-lower-b “6.0”^^xsd:float
_:vs-upper-b
_:isp
:interval specification
:normalCreatinineLevel
iao:is quality specification of
ro:has part
iao:has measurement unit label
obi:has specified value
:has value specification
uo:milligram per liter
uo:mass density unit
pato:normal
:creatinine level radlex:blood
_:bloodbfo:inheres in
Work-in-progress
:adultMales
obi:population:defined for reference population
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Applications
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Representing Context InformationLinks to examinations, images and reports.
radlex:lesion
:lesionXY
ogms:clinical finding
:cf0 iao:is_about
iao:image
:ima53
mci:examination
:exm1
:rr
obo:has_specified_output
:radiological report
:s
mci:documented in
mci:image series
:img-series1
:reports on
ro:has_part
ro:has_part :reports on
mci:documented in
bspo:transverse plane
:tpiao:is about
“53”^^xsd:integer
mci:has slice ID
mci:size findingmci:sentence
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Knowledge Model with Size SpecificationsManually created with radiologist.
Content:• 50 size specifications about 38 different RadLex concepts:
e.g. spleen, kidney, gallbladder, pancreas, lymph nodes, aorta, lesion, cyst, bile ducts etc.• Some of them are patient-specific.
Sources:• A book about normal findings1
• Radiopedia2
Data Sets:• Lymphoma patients: 2584 German radiology reports (27 different readers) of 377 patients
Imaging modality: CT, MRI, US• Internistic patients: 6007 German radiology reports (27 different readers)
Imaging modality: CT
1 T. B. Möller and E. Reif, CT- und MRT-Normalbefunde. Thieme, 1998.2 http://radiopaedia.org/
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Application 1: Information ExtractionUsing normal size specification to extract size findings from text.
Example: “Enlarged lymph node right paraaortal below the renal pedicle now 23 mm.”
Annotations:
Measurement relation resolution:1. Knowledge based:
1. Filter annotations2. Create spanning tree along RadLex subclass hierarchy3. attach available size specifications4. compare size specifications with measurement 5. compute ranking value including the concept position in Radlex
2. Sentence distance3. Statistics (based on 1000 manually annotated sentences)
Final ranking integrates results from all three approaches
Result: 2.3 cm describes the size of the inferior para-aortic lymph node.
radlex:lymphadenopathy
radlex:kidney radlex:renal pedicle
2.3 uo:centimeter
radlex:lymph node
radlex:lateral aortic lymph node radlex:inferior para-aortic lymph node
radlex:rightradlex:enlarged
radlex:inferior
radlex:paraaortic
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Evaluation of pure Knowledge based Approach
Details (to be published): “Knowledge-based Extraction of Measurement-Entity Relations from German Radiology Reports”. H. Oberkampf, C. Bretschneider, S. Zillner, B. Bauer, M. Hammon. IEEE International Conference on Healthcare Informatics 2014.
F-measure results:lymphoma dataset: 0.85internistic dataset: 0.79
anat
omic
al e
ntity
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Application 2: Normality ClassificationPatient-specific classification of normal and abnormal size findings.
Example: 52 years old patient
Given a size finding: 1D, 2D or 3D with corresponding anatomical entity.mediastinal lymph node 1.6 x 1.2 cminguinal lymph node 1.4 cmspleen 10 x 4.8 cmhead of pancreas 2.8 cm
Retrieve all patient-specific normal size specifications for closest superclass:mediastinal lymph node normal diameter of lymph node up to 1 cminguinal lymph node normal diameter of inguinal lymph node up to 1.5 cmspleen normal spleen: depth 4-6 cm, width 7-10 cm, length 11-15 cmhead of pancreas normal size of head of pancreas (for patients from 51-60 years): 21-27 mm
Check whether the values are within normal intervalabnormal: mediastinal lymph node 1.6 x 1.2 cmnormal: inguinal lymph node 1.4 cmnormal: spleen 10 x 4.8 cmabnormal: head of pancreas 2.8 cm
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Application 3: Inference of ChangeWe use SPARQL to classify size findings as progressive, regressive or stable.
• Scalar measurements can be compared directly.• For two/three directional length measurements we compare the index (e.g. spleen index: width x depth x length).
Image source: “Automated Detection and Volumetric Segmentation of the Spleen in CT Scans” M. Hammon, P. Dankerl, M. Kramer, S. Seifert, A. Tsymbal2, M. J. Costa2, R. Janka1, M. Uder1, A. Cavallaro
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Work-in-Progress: Linking FindingsLinking findings from consecutive examinations based on anatomical entity.
radlex:XXX
:anat0
obo:clinical finding
:cf0obo:is_about
:cf1 :anat1obo:is_about
Problems: Two findings about “radlex:lymph node” do not necessarily describe the same lymph node.
preceeding finding/related finding
For the current demo we linked and compared only measurements occurring within one report sentence.
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Demo
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Architecture of Demo Implementation
Triple store: Apache Jena Fuseki
/pdatanamed graphs for different examinations
/mciBFO, IAO, OGMS, MCI, BSPO, OBI, UO, PATO
/radlex
Jetty ServerUsing Java, Apache Jena, XSLT
HTTP request
SPARQL queries XML response
HTML response
Browser
RadiologyReportsFindingsSection
AssessmentSectionMeta data
parsing of annotations UIMA
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Extracted and Classified Size Findings
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Age-specific Classification of Size Findings
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Questions?
Contact:
Heiner Oberkampf James A. OvertonSiemens AG, Corporate Technology KnoceanMunich, Germany Toronto, [email protected] [email protected]
Thanks:OBI developers