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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Early steps of an Ontology for Magnetic Resonance Imaging: MRIO</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Lucas M. Serra</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Michael G. Dwyer</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>William D. Duncan</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Alexander D. Diehl</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>; Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo</institution>
          ,
          <addr-line>Buffalo</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Department of Biomedical Informatics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo</institution>
          ,
          <addr-line>Buffalo</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The Magnetic Resonance Imaging Ontology (MRIO) is an application ontology that represents numerous entities in the domain of magnetic resonance imaging (MRI) including MRI analysis and MRI sequences. Data from clinical trials MRI protocols were used to create the axioms of these MRI sequences. We have also created means for automatically loading MRI headers as new ontology instances and demonstrate the ability to query data in MRIO. The current work represents the beginnings of a full-fledged imaging ontology and automated analysis pipeline, which we plan to further develop. Future iterations of the project will include a stream-lined user-interface for querying and improved capability in classifying image types.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>MRI ontology; imaging informatics; MRIO.</p>
      <sec id="sec-1-1">
        <title>The Fundamentals of Magnetic Resonance Imaging</title>
        <p>Magnetic resonance imaging (MRI) is a mainstay of modern
medicine that has rapidly integrated itself into a myriad of
diagnostic algorithms and has proven itself as a valuable
component of healthcare due to its versatility and accuracy.
However, these features come at the cost of price and
complexity. MRI is a nuanced technology and, when
approaching methods for representing its components in an
ontology, merits an understanding of the fundamental principles
of magnetic resonance. MRI is based upon the same physical
principles that underlie nuclear magnetic resonance and is
predicated upon on the notion of “spin”. Spin gives particles,
like protons, their angular momentum and a magnetic moment
(1). Protons therefore have magnetic fields which align with
applied external magnetic fields. By interrogating these proton
spins with radiofrequency pulses and recording the responses,
MRI is able to infer many different properties of the underlying
tissue.</p>
      </sec>
      <sec id="sec-1-2">
        <title>The Anatomy of an MRI Machine</title>
        <p>Modern MRI machines are composed of a primary
superconducting magnet that supplies the main magnetic field,
a gradient coil to alter the primary magnet’s field and encode
spatial information, and a set of radiofrequency (RF) coils to
create pulses and receive signals. If we consider an analogy
where the protons are the needle of a compass, the RF coil’s
function is somewhat similar to nudging the needle with a finger
and timing how long it takes for the needle to re-right itself. As
the protons re-align themselves with the applied magnetic field,
they release energy. Protons can release energy to their
surroundings, which is referred to as spin-lattice relaxation or
T1 relaxation. Alternatively, protons can become out of phase
with each other. This is called spin-spin relaxation or T2
relaxation. Depending on which of these effects dominates an
image determines whether we designate an image as a “T1
image” or a “T2 image”. The aforementioned effects alter the
net magnetic vector within the machine, which is captured as
electrical impulses by the RF coil. In addition to these
“classical” image contrasts, the field of MRI physics has
discovered many other sources of tissue contrast that can be
elucidated by variations in the standard pulse sequence regime.
Together, these various contrasts enable fine discrimination of
tissue composition that is not possible with other imaging
modalities, which has cemented MRI as the premiere imaging
option for pathologies affecting soft tissues.</p>
      </sec>
      <sec id="sec-1-3">
        <title>Expanding Use and Standards</title>
        <p>MRI is an often-used component in a physician’s toolkit
especially in the US which boasts the second highest number of
MRI machines per capita globally (2). MRI has broad clinical
and research applications ranging from traumatic brain injuries
to osteoarthritis to malignancy. Within the past two decades, the
use of imaging across healthcare has risen dramatically, and has
been partly fueled by physicians who purchase MRI machines
for their practices and consequently order more scans (3, 4). The
growing use of imaging data has necessitated improvements in
imaging standards and protocols. Healthcare professionals and
researchers working within the field of imaging wisely adopted
a standard file format for medical images decades ago. Digital
Imaging and Communications in Medicine (DICOM) is used
worldwide to store and transmit medical images. (5). In order to
further augment the standardization and interoperability
introduced by DICOM, centers involved in clinical trials often
adopt detailed protocols, which state specific image parameters
and tolerances for use during data collection. These data exist as
numbers and text in the metadata fields of a DICOM header.</p>
      </sec>
      <sec id="sec-1-4">
        <title>Problems Facing the Field</title>
        <p>I. With increased use and widening adoption comes
evergrowing volumes of data that must be catalogued, managed, and
analyzed. Despite the progress made in standardizing medical
images, there exist numerous challenges in the management of
imaging data, which the use of an ontology helps to mitigate.</p>
        <p>The metadata fields of a DICOM file frequently represent
nonexplicit knowledge using ambiguous language. For instance,
one of the fields in the DICOM header is labeled ‘PulseTime’.</p>
        <p>The preceding fields deal with cardiac aspects of the scan such
Copyright © 2019 for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).
as ‘CardiacRepetitionTime’ and ‘ImagesPerCardiacCycle’
which may lead one to believe that ‘PulseTime’ relates to the
pulse or heart rate of the patient. This is complicated by later
fields that reference RF pulses but instead do so using language
like ‘PulseSequence’. This makes it challenging for a user who
is unfamiliar with the domain to use the data. Fully
understanding the intended meaning of the data fields involves
deep knowledge of the latest version of the DICOM
specifications, use of a third-party website, or consultation with
a domain expert. Among the most important issues is a lack of
consensus about the exact parameters that make up a specific
image type, which is partly confounded by intermachine and
inter-operator variability. The Alzheimer's Disease
Neuroimaging Initiative (ADNI) maintains highly detailed MRI
scanner protocols for use in its clinical trials and illustrates this
variability well (6). The ADNI 3 protocols define the MRI
acquisition parameters for capturing a sagittal 3D
fluidattenuated inversion recovery image of a human brain in several
different machines from different vendors. In a General Electric
25 MRI machine, the echo time (TE) is 119.0ms, the repetition
time (TR) is 4800.0ms and the inversion time (TI) is 1451ms
while in a Siemens Magnetom Verio machine the parameters are
442ms, 4800ms, and 1650ms for TE, TR, and TI respectively.</p>
        <p>Although both machines are 3 tesla MRI machines and
attempting to capture the same image, their TE parameters are
quite different. Moreover, even small changes in these
parameters can result in radically different images and
associated image types. Broadly speaking, we currently do not
have effective methods for transitioning from these elementary
imaging parameters to higher semantic levels. If we borrow an
analogy from biology, these imaging parameters are similar to
the nucleotides of DNA where different sequences can code for
the same codons and proteins. As of yet, we lack an elegant way
to determine these proteins or their functions from their
constituents. These factors can result in problems with
interoperability when combining large sets of MRI images and
the requirement to write complex and cumbersome queries to
create retrospective cohorts.</p>
      </sec>
      <sec id="sec-1-5">
        <title>Imaging Ontologies</title>
        <p>The current work is not the first ontology in the domain of
MRI images, and a handful of past studies have created
MRIrelated ontologies. NeuroLOG or OntoNeuroLOG is a French
multi-level ontology created to integrate neurological resources
from multiple academic centers and uses DOLCE as its upper
level ontology (7). NeuroLOG covers a wide array of
braincentric investigation-related entities including MRI (8). A more
recent MRI ontology covered MRI simulations and modeled the
fundamental processes of the RF pulses that form sequences (9).
Lastly, the DICOM controlled terminology is available on
BioPortal and consists of every term used in the DICOM file
format along with their definitions (10). These works suffer
from limitations in accessibility and usability. NeuroLOG is
inaccessible through the paper’s provided links and what is
viewable through snapshots of the ontology show missing
textual and logical definitions for represented entities.
NeuroLOG also uses DOLCE, which restricts its
interoperability with the multitude of existing OBO Foundry
ontologies that are grounded in the Basic Formal Ontology.
Interoperability with OBO Foundry ontologies is an important
feature that promotes reuse and prevents the creation of isolated
“data siloes”. The ontology covering MRI simulations and
sequences did not publish their ontology in any form. The
DICOM controlled terminology, although published alongside
ontologies on BioPortal, has a completely flat structure and
some of its definitions are not crafted in the style preferred by
the OBO Foundry. Additionally, all these ontologies seem to not
cover the higher levels of abstraction that we desire in our
ontology.</p>
        <p>In the current work, we have developed the MRI ontology
(MRIO) to represent MRI analyses, sequences, images, and
machines using metadata from DICOM files to create axioms.
We have also created methods for extracting this information
from DICOM headers and automatically creating new ontology
instances.</p>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>Methods</title>
      <sec id="sec-2-1">
        <title>Ontology Construction</title>
        <p>MRIO was created with the latest version of Protégé (5.5.0)
(11). The HermiT (1.4.3.456) reasoner plugin was used for
inference (12). Our ontology was built with certain principles in
mind, such as resource identifiers, textual definitions, and
openness, all of which are outlined by the Open Biological and
Biomedical Ontology (OBO) Foundry (13). Following these
principles, MRIO uses BFO as its upper level ontology and
reuses existing ontologies like the Ontology for Biomedical
Investigations (OBI) and the Information Artifact Ontology
(1416). MRIO adds 70 new terms, most with well-constructed
textual and logical definitions to represent multiple aspects of
MRI images. Around two dozen terms were reused from OBI
and IAO as upper level terms or in relations. Our ontology was
constructed in both a top-down and a bottom-up approach. The
entities we deemed most important in representing MRIs in an
ontology are: the MRI image objective and the MRI sequences,
followed by the MRI machine, the patient/evaluant, the MRI
assay, and the MRI image itself. We consulted with domain
experts in order to create the MRI analysis hierarchy. The most
salient metadata on DICOM image files are “parameter
specifications” or “acquisition parameters”, which describe RF
pulse sequences. These parameters, implemented as data
properties, were used in creating the axioms and
computerreadable definitions of sequences. A GitHub repository
containing the latest version of the ontology is available at:
https://github.com/LucasSerra1/MRIO.git</p>
      </sec>
      <sec id="sec-2-2">
        <title>Data Extraction</title>
        <p>The scripts used in parsing MRI headers and MRI protocol
files were written using the Python programming language. In
essence, the scripts extract information from the DICOM
headers and transform the information into instances of MRIO
classes and relations. DICOM header data fields are first
transformed into a spreadsheet. These fields are mapped to
MRIO data properties. Numeric values are then read and
associated with these data properties. The RDFLib (4.2.2)
Python library was used to facilitate this transformation and
automatically add graph nodes and new instances to our
ontology from these mapped classes. To create the axioms that
underlie the sequence types (Figure 2), a separate script was
created that extracts parameter specifications from JSON files
representing years of MRI study protocols used in clinical trials
conducted at the Buffalo Neuroimaging Analysis Center. As no
exact definitions for consensus sequence parameters exist in the
DICOM specifications or in published literature, simple ranges
were used to define sequence parameters and provide a survey
of the data available. Minimum and maximum values were
extracted across hundreds of entries to create the ranges that
constitute the axioms of our sequence classes.</p>
        <p>Our final output of the data extraction process was an OWL
file containing 4 instances (representing a single DICOM
header), 70 MRIO-specific classes, and 8 new data properties.
The original data consisted of 300 text files containing 1000
entries for MRI protocols (17). This was distilled into 5 MRI
pulse sequence classes in the final ontology. After modification
with RDFLib, the ontology was loaded as a triplestore into the
free version of GraphDB (8.9) Using SPARQL, we queried the
data looking for images by their parameters (18, 19).</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Results</title>
      <p>The ensemble of these moving pieces is a pipeline that
automatically loads DICOM headers and inserts them into a
queryable MRI ontology created from a combination of domain
expertise and parameter data extracted from clinical trial
protocols. Figure 3 provides an overview of the gross structure
of the ontology. As MRIO is built upon the foundations of OBI,
it takes a similar approach in establishing relationships between
the overall imaging process and the participants. Terms derived
from OBI are in ovals while MRIO terms are in boxes. More
specifically, ‘magnetic resonance imaging pulse sequence’ is
define as a type of ‘processed material’ and stands in a ‘part of’
relation to the ‘magnetic resonance imaging radiofrequency
coil’, which is an OBI ‘measurement device’. As shown in
Figure 3, both the MRI machine and a ‘material entity’ with the
‘magnetic resonance imaging evaluant role’ are the specified
inputs of a ‘magnetic resonance imaging assay’. This ‘magnetic
resonance imaging assay’ term resides under the ‘planned
process’ class and has ‘magnetic resonance imaging datum’ as
the specified output. This data undergoes a ‘magnetic resonance
imaging data transformation’, which in the real-world partly
takes the form of a Fourier transformation and results in the final
‘magnetic resonance imaging image’. The image is tied back to
the sequence used and the subject of the scan using ‘is about’
relations.</p>
      <p>Figure 1 depicts the structure of the MRI pulse sequences.
Several new data properties were needed to fully represent
sequence parameters: ‘has TR’, ‘has TE’, ‘has inversion time’,
‘has flip angle’, and ‘has echo train length’. These entities were
derived from BNAC MRI protocol specifications and represent
settings configured on an MRI machine for the creation of an
MRI image.</p>
      <p>Figure 2 illustrates the type of query one is able to use with
MRIO. With SPARQL, an investigator is able to hone in on
well-crafted cohorts via sequence parameters as in this example
or via a number of other axes.</p>
    </sec>
    <sec id="sec-4">
      <title>Discussion</title>
      <p>Our work contributes to imaging informatics in a number of
ways. The automatic creation of ontology instances mitigates the
laborious task of data entry. Our system also enables precise
selection of cohorts from datasets of DICOMs and facilitates
discovery of potential subgroups within imaging data. MRIO
provides a structured semantic representation of many of the
metadata fields found in the DICOM format. To this end, MRIO
improves the interpretability of data field definitions without the
need for external resources and elucidates some of the implicit
knowledge found within this domain. MRIO’s adherence to
OBO Foundry principles also enhances interoperability with
other similarly structured ontologies.</p>
      <p>Despite these benefits, MRIO and its extraneous systems are
currently limited in some respects. At present, MRIO can only
process single DICOM headers, which must be loaded as text
files. Furthermore, once new MRI instances are loaded, the
HermiT reasoning engine in Protégé takes minutes to sort
individuals and infer relations. This occurs with only a handful
of DICOMs loaded. We are investigating methods to speed up
the reasoning so we can scale the ontology appropriately. Our
ontology also only captures a small selection of the vast number
of data fields found within the DICOM file standard. We would
also like to more fully develop the definitions of our classes. As
a final limitation, our system requires that users understand
SPARQL to write their queries and extract information from
data loaded in triplestores, although our long-term plans include
creating a web interface to simplify querying.</p>
      <p>MRIO represents the beginnings of a full-fledged imaging
ontology and automated analysis pipeline. There are many
possibilities for future work and expanding the functionality of
MRIO. With thousands of MRIs loaded from disparate data sets
and institutions, it would be possible to better grasp which are
the exact elements that make a “T1 image”. This could occur
either through community consensus or MRIO could provide
high-quality data for machine learning or statistical treatments
of this question. In later versions of our work, the query system
could be improved with a natural language processing-based
query system and a more stream-lined user interface that would
obviate the need for users to know SPARQL.</p>
    </sec>
    <sec id="sec-5">
      <title>Conclusion</title>
      <p>MRIO is the only MRI ontology under active development.
At present, MRIO enjoys a number of useful features and
these initial steps provide a proof-of-concept for a much larger
analytic platform with numerous uses.</p>
      <sec id="sec-5-1">
        <title>ACKNOWLEDGMENT</title>
      </sec>
      <sec id="sec-5-2">
        <title>AD was supported by 5UL1TR001412 (NCATS).</title>
        <p>MD has received consultant fees from Claret Medical and EMD
Serono, and research grant support from Novartis and Celgene.
Fig 2. Example SPARQL query
image creation</p>
        <p>device
measurement
device
processed
material</p>
        <p>MRI
radiofrequency coil</p>
        <p>has part
MRI pulse
sequence</p>
        <p>MRI machine
has_specified_input
imaging assay
has part
has part
has_specified_output
MRI magnet</p>
        <p>MRI assay
has_specified_input
device
material
entity
inheres in
MRI evaluant role
evaluant role
is about
data
transformation
MRI datum
transformation
has_specified_input
has_specified_output
MRI datum
is about
measurement
datum</p>
        <p>MRI image
image
1.</p>
      </sec>
    </sec>
  </body>
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