Federico Spagnolo

Po-Jui Lu, Alessandro Cagol, Mario Ocampo-Pineda et al.

Background: The lateral ventricle choroid plexus (LVCP) is gaining recognition as a key imaging biomarker for multiple sclerosis (MS) related to physical disability and neuroinflammation. Yet, manual segmentation of the LVCP is highly tedious, restricting its use in broad clinical trials and longitudinal assessments. This research aims to develop a SwinUNETR-driven pipeline that leverages targeted intra- and peri-ventricular small patch sampling to automatically segment the LVCP in MS from both standalone and multi-modal MRI inputs. Methods: We retrospectively assessed 3T MRI scans across three sets of data stemming from two separate MS-dominant cohorts (Dataset 1: n=177; Dataset 2: n=177; expanded test set: n=388). Our method employed a SwinUNETR architecture trained on 32x32x32 voxel patches, benchmarking it against the 3D UXNET model. The primary metric for evaluation was the Dice Similarity Coefficient (DSC), supplemented by computational demand (GFLOPs) and the 95th percentile Hausdorff Distance (HD95). Results: On the extended test set, the SwinUNETR model secured a mean DSC of 0.868 (95% CI: 0.863-0.872) with MPRAGE and FLAIR combined, showing a statistically significant gain over UXNET (DSC: 0.858 [95% CI: 0.853-0.862], p<0.0001). When restricted to standalone FLAIR inputs, the transformer-based approach sustained a high DSC of 0.863, while the spatial localization of UXNET worsened considerably (HD95: 1.86 vs. 3.00 mm). Importantly, the proposed framework lowered computational load by 99% (91.8 vs. 22,080 GFLOPs). By integrating localized patch sampling with a SwinUNETR architecture, this methodology offers an accurate, robust, and statistically superior alternative to current leading models for LVCP segmentation. Its vast reduction in computational cost makes it ideal for widespread implementation in clinical and research environments.

Federico Spagnolo, Nataliia Molchanova, Mario Ocampo Pineda et al.

To date, several methods have been developed to explain deep learning algorithms for classification tasks. Recently, an adaptation of two of such methods has been proposed to generate instance-level explainable maps in a semantic segmentation scenario, such as multiple sclerosis (MS) lesion segmentation. In the mentioned work, a 3D U-Net was trained and tested for MS lesion segmentation, yielding an F1 score of 0.7006, and a positive predictive value (PPV) of 0.6265. The distribution of values in explainable maps exposed some differences between maps of true and false positive (TP/FP) examples. Inspired by those results, we explore in this paper the use of characteristics of lesion-specific saliency maps to refine segmentation and detection scores. We generate around 21000 maps from as many TP/FP lesions in a batch of 72 patients (training set) and 4868 from the 37 patients in the test set. 93 radiomic features extracted from the first set of maps were used to train a logistic regression model and classify TP versus FP. On the test set, F1 score and PPV were improved by a large margin when compared to the initial model, reaching 0.7450 and 0.7817, with 95% confidence intervals of [0.7358, 0.7547] and [0.7679, 0.7962], respectively. These results suggest that saliency maps can be used to refine prediction scores, boosting a model's performances.

Federico Spagnolo, Nataliia Molchanova, Meritxell Bach Cuadra et al.

Explainable artificial intelligence (XAI) methods have been proposed to interpret model decisions in classification and, more recently, in semantic segmentation. However, instance-level XAI for semantic segmentation, namely explanations focused on a single object among multiple instances of the same class, remains largely unexplored. Such explanations are particularly important in multi-lesional diseases to understand what drives the detection and contouring of a specific lesion. We propose instance-level explanation maps for semantic segmentation by extending SmoothGrad and Grad-CAM++ to obtain quantitative instance saliency. These methods were applied to the segmentation of white matter lesions (WMLs), a magnetic resonance imaging biomarker in multiple sclerosis. We used 4023 FLAIR and MPRAGE MRI scans from 687 patients collected at the University Hospital of Basel, Switzerland, with WML masks annotated by four expert clinicians. Three deep learning architectures, a 3D U-Net, nnU-Net, and Swin UNETR, were trained and evaluated, achieving normalized Dice scores of 0.71, 0.78, and 0.80, respectively. Instance saliency maps showed that the models relied primarily on FLAIR rather than MPRAGE for WML segmentation, with positive saliency inside lesions and negative saliency in their immediate neighborhood, consistent with clinical practice. Peak saliency values differed significantly across correct and incorrect predictions, suggesting that quantitative instance saliency may help identify segmentation errors. In conclusion, we introduce two architecture-agnostic XAI methods that provide quantitative instance-level explanations for semantic segmentation and support clinically meaningful interpretation of model decisions.