Publications by Federico Bolelli

Histopathological image analysis is a critical area of research with the potential to aid pathologists in faster and more accurate diagnoses. However, Whole-Slide Images (WSIs) present challenges for deep learning frameworks due to their large size and lack of pixel-level annotations. Multi-Instance Learning (MIL) is a popular approach that can be employed for handling WSIs, treating each slide as a bag composed of multiple patches or instances. In this work we propose Buffer-MIL, which aims at tackling the covariate shift and class imbalance characterizing most of the existing histopathological datasets. With this goal, a buffer containing the most representative instances of each disease-positive slide of the training set is incorporated into our model. An attention mechanism is then used to compare all the instances against the buffer, to find the most critical ones in a given slide. We evaluate Buffer-MIL on two publicly available WSI datasets, Camelyon16 and TCGA lung cancer, outperforming current state-of-the-art models by 2.2% of accuracy on Camelyon16.

The adoption of Multi-Instance Learning (MIL) for classifying Whole-Slide Images (WSIs) has increased in recent years. Indeed, pixel-level annotation of gigapixel WSI is mostly unfeasible and time-consuming in practice. For this reason, MIL approaches have been profitably integrated with the most recent deep-learning solutions for WSI classification to support clinical practice and diagnosis. Nevertheless, the majority of such approaches overlook the multi-scale nature of the WSIs; the few existing hierarchical MIL proposals simply flatten the multi-scale representations by concatenation or summation of features vectors, neglecting the spatial structure of the WSI. Our work aims to unleash the full potential of pyramidal structured WSI; to do so, we propose a graph-based multi-scale MIL approach, termed DAS-MIL, that exploits message passing to let information flows across multiple scales. By means of a knowledge distillation schema, the alignment between the latent space representation at different resolutions is encouraged while preserving the diversity in the informative content. The effectiveness of the proposed framework is demonstrated on two well-known datasets, where we outperform SOTA on WSI classification, gaining a +1.9% AUC and +3.3¬curacy on the popular Camelyon16 benchmark.

Whole-Slide Images (WSI) are emerging as a promising resource for studying biological tissues, demonstrating a great potential in aiding cancer diagnosis and improving patient treatment. However, the manual pixel-level annotation of WSIs is extremely time-consuming and practically unfeasible in real-world scenarios. Multi-Instance Learning (MIL) have gained attention as a weakly supervised approach able to address lack of annotation tasks. MIL models aggregate patches (e.g., cropping of a WSI) into bag-level representations (e.g., WSI label), but neglect spatial information of the WSIs, crucial for histological analysis. In the High-Grade Serous Ovarian Cancer (HGSOC) context, spatial information is essential to predict a prognosis indicator (the Platinum-Free Interval, PFI) from WSIs. Such a prediction would bring highly valuable insights both for patient treatment and prognosis of chemotherapy resistance. Indeed, NeoAdjuvant ChemoTherapy (NACT) induces changes in tumor tissue morphology and composition, making the prediction of PFI from WSIs extremely challenging. In this paper, we propose GDS-MIL, a method that integrates a state-of-the-art MIL model with a Graph ATtention layer (GAT in short) to inject a local context into each instance before MIL aggregation. Our approach achieves a significant improvement in accuracy on the ``Ome18'' PFI dataset. In summary, this paper presents a novel solution for enhancing PFI prediction in HGSOC, with the potential of significantly improving treatment decisions and patient outcomes.

Introduction: The need of accurate three-dimensional data of anatomical structures is increasing in the surgical field. The development of convolutional neural networks (CNNs) has been helping to fill this gap by trying to provide efficient tools to clinicians. Nonetheless, the lack of a fully accessible datasets and open-source algorithms is slowing the improvements in this field. In this paper, we focus on the fully automatic segmentation of the Inferior Alveolar Canal (IAC), which is of immense interest in the dental and maxillo-facial surgeries. Conventionally, only a bidimensional annotation of the IAC is used in common clinical practice. A reliable convolutional neural network (CNNs) might be timesaving in daily practice and improve the quality of assistance. Materials and methods: Cone Beam Computed Tomography (CBCT) volumes obtained from a single radiological center using the same machine were gathered and annotated. The course of the IAC was annotated on the CBCT volumes. A secondary dataset with sparse annotations and a primary dataset with both dense and sparse annotations were generated. Three separate experiments were conducted in order to evaluate the CNN. The IoU and Dice scores of every experiment were recorded as the primary endpoint, while the time needed to achieve the annotation was assessed as the secondary end-point. Results: A total of 347 CBCT volumes were collected, then divided into primary and secondary datasets. Among the three experiments, an IoU score of 0.64 and a Dice score of 0.79 were obtained thanks to the pre-training of the CNN on the secondary dataset and the creation of a novel deep label propagation model, followed by proper training on the primary dataset. To the best of our knowledge, these results are the best ever published in the segmentation of the IAC. The datasets is publicly available and algorithm is published as open-source software. On average, the CNN could produce a 3D annotation of the IAC in 6.33 s, compared to 87.3 s needed by the radiology technician to produce a bidimensional annotation. Conclusions: To resume, the following achievements have been reached. A new state of the art in terms of Dice score was achieved, overcoming the threshold commonly considered of 0.75 for the use in clinical practice. The CNN could fully automatically produce accurate three-dimensional segmentation of the IAC in a rapid setting, compared to the bidimensional annotations commonly used in the clinical practice and generated in a time-consuming manner. We introduced our innovative deep label propagation method to optimize the performance of the CNN in the segmentation of the IAC. For the first time in this field, the datasets and the source codes used were publicly released, granting reproducibility of the experiments and helping in the improvement of IAC segmentation.

Background and objectives Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. Design, setting, participants, & measurements Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid–Schiff–stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. Results We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r50.41, P,0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1)inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. Conclusions The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment.

Inferior Alveolar Nerve (IAN) canal detection has been the focus of multiple recent works in dentistry and maxillofacial imaging. Deep learning-based techniques have reached interesting results in this research field, although the small size of 3D maxillofacial datasets has strongly limited the performance of these algorithms. Researchers have been forced to build their own private datasets, thus precluding any opportunity for reproducing results and fairly comparing proposals. This work describes a novel, large, and publicly available mandibular Cone Beam Computed Tomography (CBCT) dataset, with 2D and 3D manual annotations, provided by expert clinicians. Leveraging this dataset and employing deep learning techniques, we are able to improve the state of the art on the 3D mandibular canal segmentation. The source code which allows to exactly reproduce all the reported experiments is released as an open-source project, along with this article.

The problem of prostate segmentation from Magnetic Resonance Imaging (MRI) is an intense research area, due to the increased use of MRI in the diagnosis and treatment planning of prostate cancer. The lack of clear boundaries and huge variation of texture and shapes between patients makes the task very challenging, and the 3D nature of the data makes 2D segmentation algorithms suboptimal for the task. With this paper, we propose a novel architecture to fill the gap between the most recent advances in 2D computer vision and 3D semantic segmentation. In particular, the designed model retrieves multi-scale 3D features with dilated convolutions and makes use of a self-attention transformer to gain a global field of view. The proposed Long-Range 3D Self-Attention block allows the convolutional neural network to build significant features by merging together contextual information collected at various scales. Experimental results show that the proposed method improves the state-of-the-art segmentation accuracy on MRI prostate segmentation.