pMineR: An Innovative R Library for Performing Process Mining in Medicine

Process Mining is an emerging discipline investigating tasks related with the automated identification of process models, given realworld data (Process Discovery). The analysis of such models can provide useful insights to domain experts. In addition, models of processes can be used to test if a given process complies (Conformance Checking) with specifications. For these capabilities, Process Mining is gaining importance and attention in healthcare. In this paper we introduce pMineR, an R library specifically designed for performing Process Mining in the medical domain, and supporting human experts by presenting processes in a human-readable way

Application of Artificial Neural Network to Preoperative 18F-FDG PET/CT for Predicting Pathological Nodal Involvement in Non-small-cell Lung Cancer Patients

Purpose: To evaluate the performance of artificial neural networks (aNN) applied to preoperative 18F-FDG PET/CT for predicting nodal involvement in non-small-cell lung cancer (NSCLC) patients. Methods: We retrospectively analyzed data from 540 clinically resectable NSCLC patients (333 M; 67.4 \ub1 9 years) undergone preoperative 18F-FDG PET/CT and pulmonary resection with hilo-mediastinal lymphadenectomy. A 3-layers NN model was applied (dataset randomly splitted into 2/3 training and 1/3 testing). Using histopathological reference standard, NN performance for nodal involvement (N0/N+ patient) was calculated by ROC analysis in terms of: area under the curve (AUC), accuracy (ACC), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV). Diagnostic performance of PET visual analysis (N+ patient: at least one node with uptake mediastinal blood-pool) and of logistic regression (LR) was evaluated. Results: Histology proved 108/540 (20%) nodal-metastatic patients. Among all collected data, relevant features selected as input parameters were: patients\u2019 age, tumor parameters (size, PET visual and semiquantitative features, histotype, grading), PET visual nodal result (patient-based, as N0/N+ and N0/N1/N2). Training and testing NN performance (AUC = 0.849, 0.769): ACC = 80 and 77%; SE = 72 and 58%; SP = 81 and 81%; PPV = 50 and 44%; NPV = 92 and 89%, respectively. Visual PET performance: ACC = 82%, SE = 32%, SP = 94%; PPV = 57%, NPV = 85%. Training and testing LR performance (AUC = 0.795, 0.763): ACC = 75 and 77%; SE = 68 and 55%; SP = 77 and 82%; PPV = 43 and 43%; NPV = 90 and 88%, respectively..Conclusions: aNN application to preoperative 18F-FDG PET/CT provides overall good performance for predicting nodal involvement in NSCLC patients candidate to surgery, especially for ruling out nodal metastases, being NPV the best diagnostic result; a high NPV was also reached by PET qualitative assessment. Moreover, in such population with low a priori nodal involvement probability, aNN better identify the relatively few and unexpected nodal-metastatic patients than PET analysis, so supporting the additional aNN use in case of PET-negative images

What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

[EN] In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?Gatta, R.; Vallati, M.; Fernández Llatas, C.; Martinez-Millana, A.; Orini, S.; Sacchi, L.; Lenkowicz, J.... (2020). What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper. International Journal of Environmental research and Public Health (Online). 17(18):1-19. https://doi.org/10.3390/ijerph17186616S1191718Guyatt, G. (1992). Evidence-Based Medicine. JAMA, 268(17), 2420. doi:10.1001/jama.1992.03490170092032Hripcsak, G., Ludemann, P., Pryor, T. A., Wigertz, O. B., & Clayton, P. D. (1994). Rationale for the Arden Syntax. Computers and Biomedical Research, 27(4), 291-324. doi:10.1006/cbmr.1994.1023Peleg, M. (2013). Computer-interpretable clinical guidelines: A methodological review. 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Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations. Implementation Science, 7(1). doi:10.1186/1748-5908-7-61Legido-Quigley, H., Panteli, D., Brusamento, S., Knai, C., Saliba, V., Turk, E., … Busse, R. (2012). Clinical guidelines in the European Union: Mapping the regulatory basis, development, quality control, implementation and evaluation across member states. Health Policy, 107(2-3), 146-156. doi:10.1016/j.healthpol.2012.08.004Rashidian, A., Eccles, M. P., & Russell, I. (2008). Falling on stony ground? A qualitative study of implementation of clinical guidelines’ prescribing recommendations in primary care. Health Policy, 85(2), 148-161. doi:10.1016/j.healthpol.2007.07.011Yang, W.-S., & Hwang, S.-Y. (2006). A process-mining framework for the detection of healthcare fraud and abuse. 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N., & Greenes, R. A. (1994). Improving Clinical Guidelines with Logic and Decision-table Techniques. Medical Decision Making, 14(3), 245-254. doi:10.1177/0272989x9401400306Peleg, M., Tu, S., Bury, J., Ciccarese, P., Fox, J., Greenes, R. A., … Stefanelli, M. (2003). Comparing Computer-interpretable Guideline Models: A Case-study Approach. Journal of the American Medical Informatics Association, 10(1), 52-68. doi:10.1197/jamia.m1135Karadimas, H., Ebrahiminia, V., & Lepage, E. (2018). User-defined functions in the Arden Syntax: An extension proposal. Artificial Intelligence in Medicine, 92, 103-110. doi:10.1016/j.artmed.2015.11.003Peleg, M., Keren, S., & Denekamp, Y. (2008). Mapping computerized clinical guidelines to electronic medical records: Knowledge-data ontological mapper (KDOM). Journal of Biomedical Informatics, 41(1), 180-201. doi:10.1016/j.jbi.2007.05.003German, E., Leibowitz, A., & Shahar, Y. (2009). An architecture for linking medical decision-support applications to clinical databases and its evaluation. Journal of Biomedical Informatics, 42(2), 203-218. doi:10.1016/j.jbi.2008.10.007Marcos, M., Maldonado, J. A., Martínez-Salvador, B., Boscá, D., & Robles, M. (2013). Interoperability of clinical decision-support systems and electronic health records using archetypes: A case study in clinical trial eligibility. Journal of Biomedical Informatics, 46(4), 676-689. doi:10.1016/j.jbi.2013.05.004Marco-Ruiz, L., Moner, D., Maldonado, J. A., Kolstrup, N., & Bellika, J. G. (2015). Archetype-based data warehouse environment to enable the reuse of electronic health record data. International Journal of Medical Informatics, 84(9), 702-714. doi:10.1016/j.ijmedinf.2015.05.016Gooch, P., & Roudsari, A. (2011). Computerization of workflows, guidelines, and care pathways: a review of implementation challenges for process-oriented health information systems. 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Interplay between Clinical Guidelines and Organizational Workflow Systems. Methods of Information in Medicine, 55(06), 488-494. doi:10.3414/me16-01-0006Mulyar, N., van der Aalst, W. M. P., & Peleg, M. (2007). A Pattern-based Analysis of Clinical Computer-interpretable Guideline Modeling Languages. Journal of the American Medical Informatics Association, 14(6), 781-787. doi:10.1197/jamia.m2389Grando, M. A., Glasspool, D., & Fox, J. (2012). A formal approach to the analysis of clinical computer-interpretable guideline modeling languages. Artificial Intelligence in Medicine, 54(1), 1-13. doi:10.1016/j.artmed.2011.07.001Kaiser, K., & Marcos, M. (2015). Leveraging workflow control patterns in the domain of clinical practice guidelines. BMC Medical Informatics and Decision Making, 16(1). doi:10.1186/s12911-016-0253-zMartínez-Salvador, B., & Marcos, M. (2016). Supporting the Refinement of Clinical Process Models to Computer-Interpretable Guideline Models. 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Convolutional neural network based on fluorescein angiography images for retinopathy of prematurity management

Purpose: The purpose of this study was to explore the use of fluorescein angiography (FA) images in a convolutional neural network (CNN) in the management of retinopathy of prematurity (ROP).Methods: The dataset involved a total of 835 FA images of 149 eyes (90 patients), where each eye was associated with a binary outcome (57 "untreated" eyes and 92 "treated"; 308 "untreated" images, 527 "treated"). The resolution of the images was 1600 and 1200 px in 20% of cases, whereas the remaining 80% had a resolution of 640 and 480 px. All the images were resized to 640 and 480 px before training and no other preprocessing was applied. A CNN with four convolutional layers was trained on 90% of the images (n = 752) randomly chosen. The accuracy of the prediction was assessed on the remaining 10% of images (n = 83). Keras version 2.2.0 for R with Tensorflow backend version 1.11.0 was used for the analysis.Results: The validation accuracy after 100 epochs was 0.88, whereas training accuracy was 0.97. The receiver operating characteristic (ROC) presented an area under the curve (AUC) of 0.91.Conclusions: Our study showed, we believe for the first time, the applicability of artificial intelligence (CNN) technology in the ROP management driven by FA. Further studies are needed to exploit different fields of applications of this technology.Translational Relevance: This algorithm is the basis for a system that could be applied to both ROP as well as experimental oxygen induced retinopathy

A field strength independent MR radiomics model to predict pathological complete response in locally advanced rectal cancer

PURPOSE: Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner. METHODS: In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon-Mann-Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness. RESULTS: Three features were selected: maximum fractal dimension with IB = 0-50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0-50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively. CONCLUSIONS: The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features

The image biomarker standardization initiative: Standardized convolutional filters for reproducible radiomics and enhanced clinical insights

Standardizing convolutional filters that enhance specific structures and patterns in medical imaging enables reproducible radiomics analyses, improving consistency and reliability for enhanced clinical insights. Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking

On the Feasibility of Distributed Process Mining in Healthcare

[EN] Process mining is gaining significant importance in the healthcare domain, where the quality of services depends on the suitable and efficient execution of processes. A pivotal challenge for the application of process mining in the healthcare domain comes from the growing importance of multi-centric studies, where privacy-preserving techniques are strongly needed. In this paper, building on top of the well-known Alpha algorithm, we introduce a distributed process mining approach, that allows to overcome problems related to privacy and data being spread around. The introduced technique allows to perform process mining without sharing any patients-related information, thus ensuring privacy and maximizing the possibility of cooperation among hospitals.Gatta, R.; Vallati, M.; Lenkowicz, J.; Masciocchi, C.; Cellini, F.; Boldrini, L.; Fernández Llatas, C.... (2019). On the Feasibility of Distributed Process Mining in Healthcare. Springer. 445-452. https://doi.org/10.1007/978-3-030-22750-0_36S445452van der Aalst, W.M.P., Weijters, T., Maruster, L.: Workflow mining: discovering process models from event logs. IEEE Trans. Knowl. Data Eng. 16, 1128–1142 (2004)van der Aalst, W.: Process Mining: Discovery, Conformance and Enhancement of Business Processes. Springer, Heidelberg (2011). https://doi.org/10.1007/978-3-642-19345-3van der Aalst, W., et al.: Process Mining Manifesto. In: Daniel, F., Barkaoui, K., Dustdar, S. (eds.) BPM 2011, Part I. LNBIP, vol. 99, pp. 169–194. Springer, Heidelberg (2012). https://doi.org/10.1007/978-3-642-28108-2_19Boyd, S., Parikh, N., Chu, E., Peleato, B., Eckstein, J.: Distributed optimization and statistical learning via the alternating direction method of multipliers. Found. Trends Mach. Learn. 3(1), 1–122 (2011)Damiani, A., et al.: Distributed learning to protect privacy in multi-centric clinical studiest. In: Artificial Intelligence in Medicine (2015)George, M., Selvarajan, S., Dkhar, S., Chandrasekaran, A.: Globalization of clinical trials - where are we heading? Curr. Clin. Pharmacol. 8(2), 115–123 (2013)Gresham, G., Ehrhardt, S., Meinert, J., Appel, L., Meinert, C.: Characteristics and trends of clinical trials funded by the national institutes of health between 2005 and 2015. Clin. Trials 15(1), 65–74 (2018)Lindell, Y., Pinkas, B.: Privacy preserving data mining. In: Bellare, M. (ed.) CRYPTO 2000. LNCS, vol. 1880, pp. 36–54. Springer, Heidelberg (2000). https://doi.org/10.1007/3-540-44598-6_3Peterson, J.L.: Petri net theory and the modeling of systems (1981

Artificial Intelligence and OCT Angiography in Full Thickness Macular Hole. New Developments for Personalized Medicine

Purpose: To evaluate the 1-year visual acuity predictive performance of an artificial intelligence (AI) based model applied to optical coherence tomography angiography (OCT-A) vascular layers scans from eyes with a full-thickness macular hole (FTMH). Methods: In this observational cross-sectional, single-center study, 35 eyes of 35 patients with FTMH were analyzed by OCT-A before and 1-year after surgery. Superficial vascular plexus (SVP) and deep vascular plexus (DVP) images were collected for the analysis. AI approach based on convolutional neural networks (CNN) was used to generate a continuous predictive variable based on both SVP and DPV. Different pre-trained CNN networks were used for feature extraction and compared for predictive accuracy. Results: Among the different tested models, the inception V3 network, applied on the combination of deep and superficial OCT-A images, showed the most significant differences between the two obtained image clusters defined in C1 and C2 (best-corrected visual acuity (BCVA) C1 = 66.67 (16.00 SD) and BCVA C2 = 49.10 (18.60 SD, p = 0.005). Conclusions: The AI-based analysis of preoperative OCT-A images of eyes affected by FTMH may be a useful support system in setting up visual acuity recovery prediction. The combination of preoperative SVP and DVP images showed a significant morphological predictive performance for visual acuity recovery