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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>XAI in Healthcare⋆</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Gizem Gezici</string-name>
          <email>gizem.gezici@sns.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Carlo Metta</string-name>
          <email>carlo.metta@isti.cnr.it</email>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Andrea Beretta</string-name>
          <email>andrea.beretta@isti.cnr.it</email>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Roberto Pellungrini</string-name>
          <email>roberto.pellungrini@sns.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Salvatore Rinzivillo</string-name>
          <email>rinzivillo@isti.cnr.it</email>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Dino Pedreschi</string-name>
          <email>pedre@di.unipi.it</email>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Fosca Giannotti</string-name>
          <email>fosca.giannotti@sns.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>ISTI-CNR</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Italy</string-name>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Scuola Normale Superiore</institution>
          ,
          <addr-line>Pisa</addr-line>
          ,
          <country country="IT">Italy</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>University of Pisa</institution>
          ,
          <country country="IT">Italy</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The evolution of Explainable Artificial Intelligence (XAI) within healthcare represents a crucial turn towards more transparent, understandable, and patient-centric AI applications. The main objective is not only to increase the accuracy of AI models but also, and more importantly, to establish user trust in decision support systems through improving their interpretability. This extended abstract outlines the ongoing eforts and advancements of our lab addressing the challenges brought up by complex AI systems in healthcare domain. Currently, there are four main projects: Prostate Imaging Cancer AI, Liver Transplantation &amp; Diabetes, Breast Cancer, and Doctor XAI, and ABELE.</p>
      </abstract>
      <kwd-group>
        <kwd>eol&gt;Explainable AI</kwd>
        <kwd>healthcare</kwd>
        <kwd>interpretability</kwd>
        <kwd>user trust</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
    </sec>
    <sec id="sec-2">
      <title>2. Methodology</title>
      <p>Our methodology on XAI in healthcare field combines AI technologies with healthcare domain
knowledge, and the key methodologies in our research are model-agnostic local explainers
for generating understandable and relevant explanations of model predictions on healthcare
datasets. Among these approaches, the first local explainer which works for diferent input
data types provides decision rules of influential factors and counterfactual rules. The second
approach we use specifically works on image data and returns a set of exemplar and
counterexemplar images, as well as a saliency map. Lastly, apart from the aforementioned explainers,
the third local explainer is ontology-based that works on multi-labeled sequential data. In
addition to the local explainers, we use global feature attributions to understand the overall
model behaviour.</p>
      <p>
        The key methodologies used in the following projects are related to the LORE method
proposed by Guidotti et al. [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. LORE is a powerful framework for generating local and interpretable
explanations for machine learning models. LORE utilizes a genetic algorithm to create a
synthetic neighborhood, which serves as the basis for training a local interpretable predictor. This
predictor captures the underlying logic of the model’s decision-making process, enabling the
derivation of meaningful explanations. One of the key characteristics of LORE is its ability to
provide transparent and understandable explanations for individual predictions. By focusing on
local interpretability, LORE aims to explain the reasoning behind a specific prediction rather
than the overall behavior of the model. This makes it particularly useful in situations where
interpretability at the instance level is crucial, such as in healthcare and finance.
      </p>
      <p>The explanations consist of two main components. First, a decision rule is derived from
the logic of the local interpretable predictor. This decision rule sheds light on the factors
that influenced the model’s decision, providing insights into the important features and their
corresponding weights. This information helps in understanding the key drivers behind the
prediction. Additionally, LORE produces a set of counterfactual rules as part of the explanation.
These counterfactual rules suggest modifications to the instance’s features that would lead to a
diferent outcome. By providing actionable suggestions for changing the input variables, LORE
enables users to explore what-if scenarios and understand how small changes can influence the
model’s predictions. The availability of the LORE framework, along with the accompanying
code1, facilitates its adoption and implementation in various domains. In next sections diferent
research project are described. They leverage over LORE methodology from diferent point of
views.</p>
    </sec>
    <sec id="sec-3">
      <title>3. Current Projects</title>
      <p>In this section, we briefly present our ongoing projects on XAI in healthcare by referring to the
XAI methodologies mentioned above.</p>
      <p>Prostate Imaging Cancer AI In this project, the dataset consists of T2-weighted and
Apparent Difusion Coeficient (ADC) MRI scans that were gathered in cooperation with the doctors
in Prostate Cancer Unit. To enhance knowledge of prostate cancer diagnosis, we mainly
leverage the local explainer that works on images to produce insightful justifications for intricate
imaging analyses. The project will explore the novel field of cross-domain explanations between
T2-weighted and ADC images. Through this approach, we seek to facilitate communication
1https://github.com/riccotti/LORE
between various imaging modalities and promote a more comprehensive, integrated
understanding of prostate cancer diagnosis, ultimately leading to improved patient outcomes and
management.</p>
      <p>Liver Transplantation and Diabetes This project aims to establish an Explainable CDSS
to investigate if there are some pre-liver transplantation (pre-ltx) patient characteristics that
might afect the glycemic status (condition of diabetes), i.e. if a non-diabetic patient becomes
pre-diabetic or diabetic after the liver transplantation, and also the survival of a given patient.
In this project, we work in collaboration with doctors from the Diabetology Department and we
employ the liver transplantation dataset that they collected. This tabular dataset includes 1468
patients, 470 of whom had liver transplants with follow-up data for one and five years after
the operation. The proposed pipeline is composed of two main parts: i. classification model
for the prediction tasks of diabetes and survival, ii. exploiting global and local XAI methods to
explain the overall model behaviour and individual patient predictions respectively through
pinpointing the impactful pre-ltx features.</p>
      <p>Breast Cancer In this project, the dataset consists of public health records in collaboration
with administrative institutions gathered through voluntary eforts and arranged into linked
tables that can be accessed using the SAS statistical tool developed by North Carolina State
University. Due to the size and complexity of the dataset, and the incomplete documentation,
extracting information is challenging. To address this, an entity-relationship (ER) diagram has
recently been developed as a conceptual schema to choose suitable columns and our discussions
are ongoing to identify the main research questions to which we can answer with this particular
dataset.</p>
      <p>
        Doctor XAI: Explainer for Sequential Patient Data Doctor XAI: an ontology-based approach
to black-box sequential data classification explanations [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] describes an ontology-based technique
that aims to explain black-box predicting multi-labeled, sequential, ontology-linked data. Formal
representations of knowledge called ontologies are used in the methodology to encapsulate
concepts and relationships unique to a given domain. In order to forecast the next visit, the
study concentrates on explaining Doctor AI [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ], a multilabel classifier that uses a patient’s
clinical history as input.
      </p>
      <p>
        This project aims to establish an explainable CDSS which takes the clinical history of a
patient (sequential data) and predict the next visit with a multi-label classifier. Then, leveraging
ontologies specifically the ICD-9 ontology on the MIMIC-III dataset [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ] which contains
deidentified health-related sequential data associated with over 40,000 patients who stayed in
critical care units of the Beth Israel Deaconess Medical Center between 2001 and 2012. Our
experiments on the proposed pipeline showed promising results in terms of capturing
domainspecific knowledge, extracting relevant features, and providing interpretable explanations.
Currently, we further aim to refine and expand the capabilities of the proposed pipeline by
utilizing Large Language Models (LLMs).
ABELE ABELE (Adversarial Black-box Explainer generating Latent Exemplars) [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ] is a local
model-agnostic explainer that receives a picture as input, a black-box classifier, and sets of
exemplar and counter-exemplar images along with a saliency map. Exemplars and
counterexemplars are artificially created images that are categorized with an outcome that difers from
the input image and the same outcome as the input image, respectively. To comprehend the
rationale for the choice, they can be visually examined. The input image’s regions that support
one class and those that force it into a diferent one are indicated by the saliency map. An
Adversarial Autoencoder (AAE) is used by ABELE to create a neighborhood in the latent feature
space. The encoder uses latent features to return the latent representation after receiving the
image to be explained as input from the AAE. The neighborhood generation was achieved via a
genetic technique that maximizes a fitness function. Utilizing a latent form of LORE, ABELE
benefits in this way.
      </p>
      <p>Following generation, ABELE queries the discriminator and converts the resultant image to
verify the legitimacy of every instance within the neighborhood. Following that, it uses the
picture to ask the black-box classifier for the class. By using the black-box classifier to label
the neighborhood, ABELE constructs a decision tree classifier based on the local neighborhood.
With the help of the surrogate tree, the black-box classifier’s local behavior should be mimicked.
The process facilitates the creation of exemplars and counter-exemplars by extracting the
decision rule and counter-factual rules. The quality of the encoder and decoder functions
used determines how efective ABELE is overall. The explanations will be more practical and
meaningful the higher the AAE.</p>
    </sec>
    <sec id="sec-4">
      <title>4. Conclusion</title>
      <p>The vision of our lab on XAI in healthcare is on creating a powerful, accessible, and trustworthy
AI-assisted CDSSs for healthcare professionals and patients. We believe that properly designing
the integration of XAI methodologies based on the feedback from our healthcare practitioner
collaborators is valuable. In this way, XAI can help us to foster trust, enhance decision-making,
and improve treatments for patients. Going forward, the emphasis will continue to be on
establishing CDSSs with AI in a manner that values human welfare above all else and acknowledges
the intricacies of healthcare.</p>
    </sec>
    <sec id="sec-5">
      <title>Acknowledgements</title>
      <p>This work has been supported by the European Union under ERC-2018-ADG GA 834756 (XAI),
by HumanE-AI-Net GA 952026, and by the Partnership Extended PE00000013 - “FAIR - Future
Artificial Intelligence Research” - Spoke 1 “Human-centered AI”.</p>
    </sec>
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