<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.133328.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Study Protocol</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Comparative evaluation and correlation of variations in articular disc morphology as assessed by automated segmentation using deep learning on magnetic resonance imaging (MRI) images in Class II (vertical) TMD cases, Class II (horizontal) TMD cases and Class I non-TMD cases</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Surendran</surname>
                        <given-names>Aathira</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-6943-9714</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Shrivastav</surname>
                        <given-names>Sunita</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Srivastav</surname>
                        <given-names>Gaurav</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Department of Orthodontics, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India</aff>
                <aff id="a2">
                    <label>2</label>Department of Artificial Intelligence and Data Science, Faculty of Engineering and Technology, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:aathirasurendrank@gmail.com">aathirasurendrank@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>20</day>
                <month>7</month>
                <year>2023</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2023</year>
            </pub-date>
            <volume>12</volume>
            <elocation-id>855</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>6</day>
                    <month>6</month>
                    <year>2023</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2023 Surendran A et al.</copyright-statement>
                <copyright-year>2023</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/12-855/pdf"/>
            <abstract>
                <p>
                    <bold>Introduction:</bold> Temporomandibular disorder (TMD) encompasses several clinical manifestations, which are characterized by temporomandibular joint and masticatory muscle discomfort and dysfunction (TMJ). The best imaging technique for evaluating TMJ is magnetic resonance imaging (MRI), which makes it possible to see the anatomical and pathological characteristics of every joint component. In recent years, convolutional neural networks -based deep learning algorithms have been favoured because of their outstanding capability in recognizing objects in medical images. The objective of this study is to assess, compare and co-rrelate articular disc morphology by automated segmentation using deep learning on MRI images in skeletal Class II (vertical growth pattern) TMD cases as compared to skeletal Class II (horizontal growth pattern) TMD cases and Class I non-TMD cases</p>
                <p>
                    <bold>Methods:</bold> Grading of skeletal Class II (vertical growth pattern) cases and skeletal Class II (horizontal growth pattern) cases based on severity of TMD will be carried out using diagnostic criteria for temporomandibular disorders. Bilateral sagittal as well as coronal MRI images will be obtained. A convolutional neural network (CNN) encoder-decoder named U-Net will be used to segment the articular disc on MRI. Understanding the nature of variations between Class I and both types of Class IIs will help orthodontists to better predict the potential risk for the development of TMDs and accordingly take precautions while doing treatment in such cases. Moreover, it can be used to automate TMD diagnosis and other smart applications.</p>
                <p>
                    <bold>Conclusions:</bold> This study will aid in identifying articular disc morphology on MRI. The deep learning algorithms with effective data augmentation may perform better in MRI readings than human clinicians when using the same data, which will be advantageous for TMD diagnosis.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>temporomandibular disorder</kwd>
                <kwd>TMD</kwd>
                <kwd>articular disc</kwd>
                <kwd>Class II TMD cases</kwd>
                <kwd>automated segmentation</kwd>
                <kwd>deep neural network</kwd>
                <kwd>convolutional neural network</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec1" sec-type="intro">
            <title>Introduction</title>
            <sec id="sec2">
                <title>Background and rationale</title>
                <p>Temporomandibular disorder (TMD) encompasses several clinical manifestations which is characterized by temporomandibular joint and masticatory muscle discomfort and dysfunction (TMJ).
                    <sup>
                        <xref ref-type="bibr" rid="ref1">1</xref>
                    </sup> TMD is frequently characterized by facial and pre-auricular regional pain, malocclusion, limited jaw movement, and clicking and locking of the TMJ.
                    <sup>
                        <xref ref-type="bibr" rid="ref2">2</xref>
                    </sup>
                </p>
                <p>The expected incidence rate of TMD at first onset is 3.9%, with mild to severe pain and impairment, based on an American prospective cohort study of the general public. In industrialized nations, it affects 5&#x2013;12% of the population.
                    <sup>
                        <xref ref-type="bibr" rid="ref3">3</xref>
                    </sup> As reported previously in the literature, TMD is more common in cases with skeletal Class II (vertical growth pattern) followed by skeletal Class II (horizontal growth pattern) as compared to Class I cases. This was first reported by Pancherz in 1999.
                    <sup>
                        <xref ref-type="bibr" rid="ref4">4</xref>
                    </sup>
                </p>
                <p>The best imaging technique for evaluating TMJ is magnetic resonance imaging (MRI), which makes it possible to see both the anatomical and pathological characteristics of every joint component. The shape and location of the articular disc, the mandibular condyle&#x2019;s shape and surface characteristics, atypical bone marrow signal in the mandible and temporal bone can all be assessed using an MRI.
                    <sup>
                        <xref ref-type="bibr" rid="ref5">5</xref>
                    </sup> Disc displacement or deformation, an intracapsular condition affecting the disc-condylar complex, is one of the most prominent subgroups in individuals with TMD who have articular abnormality, with an incidence of 30&#x2013;60%. An MRI is necessary for assessing variations in articular disc morphology and to predict the treatment outcome.
                    <sup>
                        <xref ref-type="bibr" rid="ref3">3</xref>
                    </sup>
                </p>
                <p>Artificial intelligence (AI)-based dental applications have been researched to simplify dental care and enhance the health of more cases at a cheap cost and are attracting interest in a variety of clinical fields. By implementing AI-based dental applications, dental professionals can reduce the amount of time they spend performing regular tasks, which will enable them to provide more individualized, preventive, and collaborative dental care. In recent years, convolutional neural networks (CNN)-based deep learning algorithms have been more favoured because of their outstanding capabilities to recognize objects in medical images. Furthermore, as computational power has increased and open-source frameworks have become more common, CNN development has been dramatically facilitated. As a result, for detection and segmentation purposes, deep learning has been extensively used, showing encouraging results. There have been reports of a number of deep neural network topologies, including the CNN-derived fully convolutional network&#x2019;s U-Net and SegNet variants.
                    <sup>
                        <xref ref-type="bibr" rid="ref6">6</xref>
                    </sup>
                </p>
                <p>Clinicians and radiologists will be able to save time and interpret pictures more accurately if they can correctly identify the TMJ area&#x2019;s major structures on MRI imaging. It can also be the basis for a lot of clever applications, including automatically diagnosing TMDs. It is without doubt important to accomplish this goal to automatically segregate TMJ structures from MRI images. Using these deep learning techniques, the mandibular condyle, articular eminence, and TMJ articular disc all are automatically detected. The TMJ segmentation of anatomical features in MRI volumes is made innovative in the current diagnostic image analysis investigation employing CNN-based DL methods.</p>
            </sec>
            <sec id="sec3">
                <title>Objectives</title>
                <p>
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>To evaluate articular disc morphology in Class I (Non-TMD) cases, skeletal Class II (vertical growth pattern) TMD cases, skeletal Class II (horizontal growth pattern) TMD cases.</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>To compare articular disc morphology in skeletal Class II (vertical growth pattern) TMD cases with skeletal Class II (horizontal growth pattern) TMD cases and Class I (Non-TMD) cases.</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>To correlate the variation in articular disc morphology with skeletal pattern.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
        </sec>
        <sec id="sec4">
            <title>Protocol</title>
            <sec id="sec5">
                <title>Study design and setting</title>
                <p>An observational and analytical study will be conducted at Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research (DMIHER), Sawangi, Wardha, Maharashtra in collaboration with the Faculty of Engineering and Technology (FEAT), DMIHER and the Department of Radiology, Acharya Vinobha Bhave Rural Hospital (AVBRH), Sawangi, Wardha.</p>
                <p>A total of 90 adult cases (Class I, Class II (vertical and horizontal growth pattern)) will be chosen from the Sharad Pawar Dental College&#x2019;s outpatient department (OPD) of orthodontics and dentofacial orthopaedics in Sawangi, Wardha.</p>
            </sec>
            <sec id="sec6">
                <title>Participants</title>
                <p>
                    <italic toggle="yes">Inclusion criteria</italic>
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Class I malocclusion cases.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Skeletal Class II (vertical growth pattern) and TMD cases.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Cases with skeletal Class II (horizontal growth pattern) and TMD.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Cases with permanent dentition.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Older than 18 years of age.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>The cases will be classified into Class I and Class II (vertical and horizontal) by cephalometric measurements as shown in the 
                                <xref ref-type="table" rid="T1">Table 1</xref>.</p>
                        </list-item>
                    </list>
                </p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>Table 1. </label>
                    <caption>
                        <title>Cephalometric parameters for case selection of Class I and Class II (vertical and horizontal growth).</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Cephalometric measurements</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Class I</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Class II (vertical)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Class II (horizontal)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">ANB angle</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;2&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;2&#x00b0;</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Wits appraisal</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0&#x2013;1 mm</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;2 mm</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;2 mm</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Frankfort mandibular plane angle</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">22&#x2013;28&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;30&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;20&#x00b0;</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Beta angle</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">27&#x2013;33&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;25&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;25&#x00b0;</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Mandibular plane angle</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">17&#x2013;28&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;28&#x00b0;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;28&#x00b0;</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>
                    <italic toggle="yes">Exclusion criteria</italic>
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Skeletal Class II (vertical growth pattern) non-TMD cases.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Non-TMD Class II (horizontal growth pattern) cases.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Class III cases.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Cases with myofascial pain dysfunction (MPD) and myalgia.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Prior treatment involving temporomandibular joint surgery.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Cases with any skeletal disorders such as cherubism, osteoporosis.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
        </sec>
        <sec id="sec7" sec-type="methods">
            <title>Methods</title>
            <p>The patient will be diagnosed according to the diagnostic criteria for temporomandibular disorders (DC/TMD). Each participant will be asked for their written, informed consent. Based on the severity of TMD, skeletal Class II (vertical and horizontal growth pattern) cases will be graded using DC/TMD criteria. Both bilateral saggital and coronal MRI images will be obtained.</p>
            <p>The articular disc of the TMJ on MRI will be identified and manually segmented with the help of technical expertise from the Faculty of Artificial Intelligence and Machine Learning (AIML) at FEAT College, Datta Meghe Institute of Higher Education and Research. After segmentation those images will be used as the dataset. The dataset showing the normal position of articular discs will be randomly split into a training data set and test set. To reduce the overfitting of the network, the dropout layer is placed behind the convolutional layers and max-pooling layers. Region of interests around the articular disc will be extracted from the datasets.</p>
            <p>Region of interests will be automatically cropped from the images using 
                <ext-link ext-link-type="uri" xlink:href="https://www.python.org/">Python</ext-link> 3.11 algorithms. Convolutional neural network (CNN) encoder-decoder named 
                <ext-link ext-link-type="uri" xlink:href="https://github.com/arnab39/FewShot_GAN-Unet3D">U-Net</ext-link> model architecture using the software 
                <ext-link ext-link-type="uri" xlink:href="https://code.visualstudio.com/">Visual Studio Code</ext-link> with the Python programming language will be used to segment the articular disc on MRI. The variation in articular disc morphology will be evaluated and compared in Class II (vertical and horizontal growth pattern) with Class I Non-TMD cases using deep learning algorithms on MRI.</p>
            <sec id="sec8">
                <title>Outcomes</title>
                <p>Primary outcome: To evaluate articular disc morphology in skeletal class II vertical and horizontal growth pattern.</p>
                <p>Secondary outcome: To compare and correlate the variation in articular disc morphology with skeletal pattern.</p>
                <p>Tertiary outcome: For doctors and radiologists, the ability to precisely recognise important features in MRI of the TMJ region will save time and increase accuracy. Also understanding the nature of variations between Class I and both types of Class IIs will help orthodontists to better predict the potential risk for development of TMDs and accordingly take precautions while carrying out treatment in such cases. Moreover, it can be used to automate TMD diagnosis and other smart applications. This is why automated segmentation of TMJ structures with MRI is clearly necessary.</p>
            </sec>
            <sec id="sec9">
                <title>Bias</title>
                <p>Bias will be minimized by random selection of patients based on the inclusion and exclusion criteria.</p>
            </sec>
            <sec id="sec10">
                <title>Study sample</title>
                <p>The calculation of sample size was carried out as follows:</p>
                <p>Formula using mean difference
                    <disp-formula id="e1">
                        <mml:math display="block">
                            <mml:mi>n</mml:mi>
                            <mml:mn>1</mml:mn>
                            <mml:mo>=</mml:mo>
                            <mml:mi>n</mml:mi>
                            <mml:mn>2</mml:mn>
                            <mml:mo>=</mml:mo>
                            <mml:mn>2</mml:mn>
                            <mml:mfrac>
                                <mml:mrow>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:mrow>
                                                <mml:msub>
                                                    <mml:mi>Z</mml:mi>
                                                    <mml:mi>&#x03b1;</mml:mi>
                                                </mml:msub>
                                                <mml:mo>+</mml:mo>
                                                <mml:msub>
                                                    <mml:mi>Z</mml:mi>
                                                    <mml:mi>&#x03b2;</mml:mi>
                                                </mml:msub>
                                            </mml:mrow>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                    <mml:msup>
                                        <mml:mi>&#x03c3;</mml:mi>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                </mml:mrow>
                                <mml:msup>
                                    <mml:mfenced close=")" open="(">
                                        <mml:mi>&#x03b4;</mml:mi>
                                    </mml:mfenced>
                                    <mml:mn>2</mml:mn>
                                </mml:msup>
                            </mml:mfrac>
                        </mml:math>
                    </disp-formula>
                </p>
                <p>Z
                    <sub>&#x03b1;</sub> = 1.64</p>
                <p>&#x03b1; = Type I error at 5% at both sides two tailed</p>
                <p>&#x0396;
                    <sub>&#x03b2;</sub> = 0.84 (1 - &#x03b2;) = power at 80%</p>
                <p>&#x03c3; = standard deviation</p>
                <p>Primary variable: Articular disc variation (mm)</p>
                <p>Class I TMD group = 1.38 &#x00b1; 0.20 (John 
                    <italic toggle="yes">et al</italic>. (2020)
                    <sup>
                        <xref ref-type="bibr" rid="ref7">7</xref>
                    </sup>)</p>
                <p>Class II (horizontal growth) TMD (mm)) group = 1.51 &#x00b1; 0.20 (John 
                    <italic toggle="yes">et al</italic>. (2020)
                    <sup>
                        <xref ref-type="bibr" rid="ref7">7</xref>
                    </sup>)</p>
                <p>Clinically relevant difference = 0.13</p>
                <p>Pooled standard deviation = (0.20+0.20)/2 = 0.2
                    <disp-formula id="e2">
                        <mml:math display="block">
                            <mml:mtext>N1</mml:mtext>
                            <mml:mo>=</mml:mo>
                            <mml:msup>
                                <mml:mn>2</mml:mn>
                                <mml:mo>&#x2217;</mml:mo>
                            </mml:msup>
                            <mml:mfenced close="]" open="[">
                                <mml:mrow>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:mrow>
                                                <mml:mn>1.64</mml:mn>
                                                <mml:mo>+</mml:mo>
                                                <mml:mn>0.84</mml:mn>
                                            </mml:mrow>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:mn>0.2</mml:mn>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                </mml:mrow>
                            </mml:mfenced>
                            <mml:mo>/</mml:mo>
                            <mml:msup>
                                <mml:mfenced close=")" open="(">
                                    <mml:mn>0.13</mml:mn>
                                </mml:mfenced>
                                <mml:mn>2</mml:mn>
                            </mml:msup>
                            <mml:mo>=</mml:mo>
                            <mml:mn>30</mml:mn>
                        </mml:math>
                    </disp-formula>
                </p>
                <p>Total samples required = 30 per group.</p>
                <p>Total sample size = 90</p>
                <p>The sample would be divided into three groups based on the inclusion and exclusion criteria:</p>
                <p>Group A (control group): 30 Class I (Non-TMD) cases.</p>
                <p>Group B: 30 skeletal Class II (vertical growth pattern) cases.</p>
                <p>Group C: 30 skeletal Class II (horizontal growth pattern) cases.</p>
            </sec>
            <sec id="sec11">
                <title>Statistical analyses</title>
                <p>All the demographic outcome data will be presented using descriptive statistics for categorial variables in terms of frequency and percentage for continuous variables in terms of mean, standard deviation and median. Results will be analysed using 
                    <ext-link ext-link-type="uri" xlink:href="https://www.ibm.com/products/spss-statistics">SPSS</ext-link> version 27 (RRID:SCR_019096) for statistical analysis. Outcome variables will be tested for normality using the Kolmogorov-Smirnov test for continuous data.</p>
                <p>All the samples will be distributed amongst the category of Class I non-TMD, Class II (vertical growth pattern) TMD cases and Class II (horizontal growth pattern) TMD cases as per the cephalometric measurements. Articular disc variation at different positions will be evaluated between these three groups using ANOVA or Kruskal Wallis test.</p>
                <p>ANOVA or a Kruskal Wallis test will be used to find the result amongst the three groups for the outcome variable for the significance in mean difference. If the data are normally distributed an ANOVA test will be used and if the data are not normally distributed a non-parametric test (Kruskal Wallis) will be used to find the significant difference.</p>
            </sec>
            <sec id="sec12">
                <title>Dissemination</title>
                <p>The original research will be published in a research article of an index journal. To ensure the original study receives the most exposure possible, the trial results will be released as open access.</p>
            </sec>
            <sec id="sec13">
                <title>Study status</title>
                <p>The deep learning model is currently being prepared and the study will commence in May 2023.</p>
            </sec>
        </sec>
        <sec id="sec14" sec-type="discussion">
            <title>Discussion</title>
            <p>Nowadays, a lot of people have TMD due to the increased stress brought on by our fast-paced society. TMD is regarded as a collection of orofacial joint and muscle problems marked by pain, abnormal joint noises, and uneven jaw function. Although only 30% of subjects may be aware of such symptoms, the majority of research show that at least 50% of people have at least one symptom (such as muscle tenderness or joint clicking).
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
            </p>
            <p>There is variation in the morphology of the hard and soft tissue structures of TMJ specially of the articular disc. At times visualization and clarity of joint morphology and the articular disc may hinder the accuracy of diagnosis. What is the extent of variation and what type of disc morphology may cause a higher potential risk of TMD needs to be explored for early and more accurate prediction.</p>
            <p>Hirata 
                <italic toggle="yes">et al</italic>. (2007) studied the articular disc shape and location in patients with disc displacement, as well as the shape of the temporomandibular joint&#x2019;s articular eminence. In the study, 14 individuals with bilateral disc displacement and no unilateral reduction were included. For evaluation, they employed magnetic resonance scans and showed that the chance of non-reducing disc displacement may be influenced by the shape of the articular disc and eminence.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup>
            </p>
            <p>In 2020, John 
                <italic toggle="yes">et al</italic>., observed that a Class II condition with a vertical growth pattern had the highest probability of developing a TMD with internal disk derangements and reduced anterior and posterior joint spaces compared to Class II with a horizontal growth pattern or Class I condition.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>Ito 
                <italic toggle="yes">et al.</italic> (2022), conducted a study that assessed fully segmentation of the temporomandibular joint&#x2019;s articular disc by automated means. Ten patients with anterior disc displacement and ten healthy control participants with normal articular discs were enrolled in the study. On MRI, they applied a semantic segmentation method based on deep learning. The study showed that this method for segmenting articular discs using automated deep learning on MRI generated encouraging preliminary results suggesting that the approach might be employed in clinical practice for the evaluation of temporomandibular disorders.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>Based on the findings of these previous studies, this planned study would enable us to recognize changes in articular disc shape, changes in articular disc location, and morphological abnormalities that can be evaluated by the deep learning network. The outcome of the treatment and diagnostic efficiency for TMD&#x2019;s may improve using this technique.</p>
            <sec id="sec15">
                <title>Ethical considerations</title>
                <p>Ethical approval has been granted by the Institutional Review Board of Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha. (Reference number: DMIHER (DU)/IEC/2023/570 on 06/02/2023).</p>
            </sec>
        </sec>
    </body>
    <back>
        <sec id="sec18" sec-type="data-availability">
            <title>Data availability</title>
            <sec id="sec19">
                <title>Underlying data</title>
                <p>No data are associated with this article.</p>
            </sec>
            <sec id="sec20">
                <title>Reporting guidelines</title>
                <p>Zenodo: STROBE checklist for &#x2018;Comparative evaluation and correlation of variations in articular disc morphology as assessed by automated segmentation using deep learning on magnetic resonance imaging (MRI) images in Class II (vertical) temporomandibular joint (TMD) cases, Class II (horizontal) TMD cases and Class I non-TMD cases&#x2019;, 
                    <ext-link ext-link-type="uri" xlink:href="https://www.doi.org/10.5281/zenodo.7853465">https://www.doi.org/10.5281/zenodo.7853465</ext-link>.</p>
                <p>Data are available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link> (CC-BY 4.0)</p>
            </sec>
        </sec>
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    <sub-article article-type="reviewer-report" id="report232583">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.146307.r232583</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Ferrillo</surname>
                        <given-names>Martina</given-names>
                    </name>
                    <xref ref-type="aff" rid="r232583a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r232583a1">
                    <label>1</label>University of Catanzaro, Catanzaro, Italy</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>12</day>
                <month>2</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Ferrillo M</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport232583" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.133328.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>Temporomandibular disorders (TMD) are a collective of various symptoms caused by abnormalities in the temporomandibular joint (TMJ) and related structures. It affects 20% to 40% of the general population. Lifestyle habits, like alcohol consumption and smoking, are considered to be linked to TMD. This study aimed to assess, compare and co-relate articular disc morphology by automated segmentation using deep learning on MRI images in skeletal Class II (vertical growth pattern) TMD cases as compared to skeletal Class II (horizontal growth pattern) TMD cases and Class I non-TMD cases.</p>
            <p> </p>
            <p> The study is of scientific interest and in line with the aims of the Journal. However, there are some issues that should be added.</p>
            <p> </p>
            <p> I suggest improving the abstract section: 
                <list list-type="bullet">
                    <list-item>
                        <p>&#x201c;temporomandibular joint and masticatory muscle discomfort and dysfunction (TMJ).&#x201d; Please move &#x201c;(TMJ)&#x201d; after &#x201c;temporomandibular joint&#x201d;.</p>
                    </list-item>
                </list> </p>
            <p> I suggest improving the introduction section on TMD: 
                <list list-type="bullet">
                    <list-item>
                        <p>Classification. Please refer to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Thus, report that TMD could be divided in Group I: muscle disorders (including myofascial pain with and without mouth opening limitation); Group II: including disc displacement with or without reduction and mouth opening limitation; Group III: arthralgia, arthritis, and arthrosis.). (cite and refer to: Schiffman 
                            <italic>et al.</italic>, 2014
                            <sup>
                                <xref ref-type="bibr" rid="rep-ref-232583-1">1</xref>
                            </sup>).</p>
                    </list-item>
                    <list-item>
                        <p>&#x00a0;&#x201c;and pre-auricular regional pain, malocclusion, limited jaw movement, and clicking and locking of the TMJ &#x201c;. Please report that TMD patients may present overlapping symptoms whit other chronic pain conditions, including headache, fibromylagia, and neurological conditions, probably through the phenomenon of central sensitization (mainly allodynia and hyperalgesia).</p>
                    </list-item>
                    <list-item>
                        <p>Please report more recent literature on conservative approaches and report new proposed treatment in the scientific literature (Agostini 
                            <italic>et al.</italic>, 2023
                            <sup>
                                <xref ref-type="bibr" rid="rep-ref-232583-2">2</xref>
                            </sup>; Madani 
                            <italic>et al.</italic>, 2020
                            <sup>
                                <xref ref-type="bibr" rid="rep-ref-232583-3">3</xref>
                            </sup>).</p>
                    </list-item>
                </list> Methods: 
                <list list-type="bullet">
                    <list-item>
                        <p>&#x201c;A total of 90 adult cases&#x201d; - Please move this information in the Result Section.</p>
                    </list-item>
                    <list-item>
                        <p>Use in all the text and tables &#x201c;P&#x201d; or &#x201c;p-value&#x201d;.</p>
                    </list-item>
                    <list-item>
                        <p>Class II patients were assessed using ANB or Wits? Or Both? Please specify.</p>
                    </list-item>
                    <list-item>
                        <p>The same question for Class I.</p>
                    </list-item>
                    <list-item>
                        <p>Add reference for DC/TMD.</p>
                    </list-item>
                </list> </p>
            <p> Results are well described.</p>
            <p> Discussion should be improved reposting more recent literature on this topic.</p>
            <p>Is the study design appropriate for the research question?</p>
            <p>Yes</p>
            <p>Is the rationale for, and objectives of, the study clearly described?</p>
            <p>Yes</p>
            <p>Are sufficient details of the methods provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Are the datasets clearly presented in a useable and accessible format?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Temporomandibular disorders</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <back>
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        <sub-article article-type="response" id="comment11971-232583">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Surendran</surname>
                            <given-names>Aathira</given-names>
                        </name>
                        <aff>Orthodontics, Sharad Pawar Dental College, Datta Meghe Institute of HIgher Education and Research, Wardha, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>6</day>
                    <month>7</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you ma'am for your thorough analysis of my article. I have made the following changes based on your review.</p>
                <p> </p>
                <p> 1.&#x00a0;Classification. Please refer to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Thus, report that TMD could be divided in Group I: muscle disorders (including myofascial pain with and without mouth opening limitation); Group II: including disc displacement with or without reduction and mouth opening limitation; Group III: arthralgia, arthritis, and arthrosis.). (cite and refer to: Schiffman&#x00a0;
                    <italic>et al.</italic>, 2014
                    <ext-link ext-link-type="uri" xlink:href="https://f1000research.com/articles/12-855/v1#rep-ref-232583-1">
                        <sup>1</sup>
                    </ext-link>).</p>
                <p> </p>
                <p> Response- i have included this in the introduction section.</p>
                <p> </p>
                <p> 2. &#x201c;and pre-auricular regional pain, malocclusion, limited jaw movement, and clicking and locking of the TMJ &#x201c;. Please report that TMD patients may present overlapping symptoms whit other chronic pain conditions, including headache, fibromylagia, and neurological conditions, probably through the phenomenon of central sensitization (mainly allodynia and hyperalgesia).</p>
                <p> </p>
                <p> Response- i have reported it.</p>
                <p> </p>
                <p> 3. Please report more recent literature on conservative approaches and report new proposed treatment in the scientific literature (Agostini&#x00a0;
                    <italic>et al.</italic>, 2023
                    <ext-link ext-link-type="uri" xlink:href="https://f1000research.com/articles/12-855/v1#rep-ref-232583-2">
                        <sup>2</sup>
                    </ext-link>; Madani&#x00a0;
                    <italic>et al.</italic>, 2020
                    <ext-link ext-link-type="uri" xlink:href="https://f1000research.com/articles/12-855/v1#rep-ref-232583-3">
                        <sup>3</sup>
                    </ext-link>).</p>
                <p> </p>
                <p> Response- I have added this literature in the introduction</p>
                <p> </p>
                <p> 4. Methods: 
                    <list list-type="bullet">
                        <list-item>
                            <p>&#x201c;A total of 90 adult cases&#x201d; - Please move this information in the Result Section</p>
                        </list-item>
                        <list-item>
                            <p>Use in all the text and tables &#x201c;P&#x201d; or &#x201c;p-value&#x201d;.</p>
                        </list-item>
                        <list-item>
                            <p>Class II patients were assessed using ANB or Wits? Or Both? Please specify.</p>
                        </list-item>
                        <list-item>
                            <p>The same question for Class I.</p>
                        </list-item>
                        <list-item>
                            <p>Add reference for DC/TMD</p>
                        </list-item>
                    </list> Response- as this is a study protocol there isn't a result section so I couldn't move the information of total cases.</p>
                <p> I have made the corrections like specified the method used for assessing Class II and Class I patients and have added the reference for DC/TMD.</p>
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