MADGAN: unsupervised medical anomaly detection GAN using multiple adjacent brain MRI slice reconstruction.

BACKGROUND: Unsupervised learning can discover various unseen abnormalities, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with either disease stages, various (i.e., more than two types of) diseases, or multi-sequence magnetic resonance imaging (MRI) scans. RESULTS: We propose unsupervised medical anomaly detection generative adversarial network (MADGAN), a novel two-step method using GAN-based multiple adjacent brain MRI slice reconstruction to detect brain anomalies at different stages on multi-sequence structural MRI: (Reconstruction) Wasserstein loss with Gradient Penalty + 100 [Formula: see text] loss-trained on 3 healthy brain axial MRI slices to reconstruct the next 3 ones-reconstructs unseen healthy/abnormal scans; (Diagnosis) Average [Formula: see text] loss per scan discriminates them, comparing the ground truth/reconstructed slices. For training, we use two different datasets composed of 1133 healthy T1-weighted (T1) and 135 healthy contrast-enhanced T1 (T1c) brain MRI scans for detecting AD and brain metastases/various diseases, respectively. Our self-attention MADGAN can detect AD on T1 scans at a very early stage, mild cognitive impairment (MCI), with area under the curve (AUC) 0.727, and AD at a late stage with AUC 0.894, while detecting brain metastases on T1c scans with AUC 0.921. CONCLUSIONS: Similar to physicians' way of performing a diagnosis, using massive healthy training data, our first multiple MRI slice reconstruction approach, MADGAN, can reliably predict the next 3 slices from the previous 3 ones only for unseen healthy images. As the first unsupervised various disease diagnosis, MADGAN can reliably detect the accumulation of subtle anatomical anomalies and hyper-intense enhancing lesions, such as (especially late-stage) AD and brain metastases on multi-sequence MRI scans

A fully automatic approach for multimodal PET and MR image segmentation in gamma knife treatment planning

Background and objectives: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. Methods: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife\uae treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment, the feasibility and the clinical value of BTV integration in Gamma Knife treatment planning were considered. Therefore, a qualitative evaluation was carried out by three experienced clinicians. Results: The achieved experimental results showed that GTV and BTV segmentations are statistically correlated (Spearman's rank correlation coefficient: 0.898) but they have low similarity degree (average Dice Similarity Coefficient: 61.87 \ub1 14.64). Therefore, volume measurements as well as evaluation metrics values demonstrated that MRI and PET convey different but complementary imaging information. GTV and BTV could be combined to enhance treatment planning. In more than 50% of cases the CTV was strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI enhanced the CTV more accurately than BTV in 25% of cases. Conclusions: The proposed fully automatic multimodal PET/MRI segmentation method is a valid operator-independent methodology helping the clinicians to define a CTV that includes both metabolic and morphologic information. BTVMRI and GTV should be considered for a comprehensive treatment planning

A fully automatic approach for multimodal PET and MR image segmentation in gamma knife treatment planning

Background and objectives: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. Methods: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment, the feasibility and the clinical value of BTV integration in Gamma Knife treatment planning were considered. Therefore, a qualitative evaluation was carried out by three experienced clinicians. Results: The achieved experimental results showed that GTV and BTV segmentations are statistically correlated (Spearman's rank correlation coefficient: 0.898) but they have low similarity degree (average Dice Similarity Coefficient: 61.87 ± 14.64). Therefore, volume measurements as well as evaluation metrics values demonstrated that MRI and PET convey different but complementary imaging information. GTV and BTV could be combined to enhance treatment planning. In more than 50% of cases the CTV was strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI enhanced the CTV more accurately than BTV in 25% of cases. Conclusions: The proposed fully automatic multimodal PET/MRI segmentation method is a valid operator-independent methodology helping the clinicians to define a CTV that includes both metabolic and morphologic information. BTVMRI and GTV should be considered for a comprehensive treatment planning

IMAGE PROCESSING, SEGMENTATION AND MACHINE LEARNING MODELS TO CLASSIFY AND DELINEATE TUMOR VOLUMES TO SUPPORT MEDICAL DECISION

Techniques for processing and analysing images and medical data have become the main’s translational applications and researches in clinical and pre-clinical environments. The advantages of these techniques are the improvement of diagnosis accuracy and the assessment of treatment response by means of quantitative biomarkers in an efficient way. In the era of the personalized medicine, an early and efficacy prediction of therapy response in patients is still a critical issue. In radiation therapy planning, Magnetic Resonance Imaging (MRI) provides high quality detailed images and excellent soft-tissue contrast, while Computerized Tomography (CT) images provides attenuation maps and very good hard-tissue contrast. In this context, Positron Emission Tomography (PET) is a non-invasive imaging technique which has the advantage, over morphological imaging techniques, of providing functional information about the patient’s disease. In the last few years, several criteria to assess therapy response in oncological patients have been proposed, ranging from anatomical to functional assessments. Changes in tumour size are not necessarily correlated with changes in tumour viability and outcome. In addition, morphological changes resulting from therapy occur slower than functional changes. Inclusion of PET images in radiotherapy protocols is desirable because it is predictive of treatment response and provides crucial information to accurately target the oncological lesion and to escalate the radiation dose without increasing normal tissue injury. For this reason, PET may be used for improving the Planning Treatment Volume (PTV). Nevertheless, due to the nature of PET images (low spatial resolution, high noise and weak boundary), metabolic image processing is a critical task. The aim of this Ph.D thesis is to develope smart methodologies applied to the medical imaging field to analyse different kind of problematic related to medical images and data analysis, working closely to radiologist physicians. Various issues in clinical environment have been addressed and a certain amount of improvements has been produced in various fields, such as organs and tissues segmentation and classification to delineate tumors volume using meshing learning techniques to support medical decision. In particular, the following topics have been object of this study: • Technique for Crohn’s Disease Classification using Kernel Support Vector Machine Based; • Automatic Multi-Seed Detection For MR Breast Image Segmentation; • Tissue Classification in PET Oncological Studies; • KSVM-Based System for the Definition, Validation and Identification of the Incisinal Hernia Reccurence Risk Factors; • A smart and operator independent system to delineate tumours in Positron Emission Tomography scans; 3 • Active Contour Algorithm with Discriminant Analysis for Delineating Tumors in Positron Emission Tomography; • K-Nearest Neighbor driving Active Contours to Delineate Biological Tumor Volumes; • Tissue Classification to Support Local Active Delineation of Brain Tumors; • A fully automatic system of Positron Emission Tomography Study segmentation. This work has been developed in collaboration with the medical staff and colleagues at the: • Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi (DIBIMED), University of Palermo • Cannizzaro Hospital of Catania • Istituto di Bioimmagini e Fisiologia Molecolare (IBFM) Centro Nazionale delle Ricerche (CNR) of Cefalù • School of Electrical and Computer Engineering at Georgia Institute of Technology The proposed contributions have produced scientific publications in indexed computer science and medical journals and conferences. They are very useful in terms of PET and MRI image segmentation and may be used daily as a Medical Decision Support Systems to enhance the current methodology performed by healthcare operators in radiotherapy treatments. The future developments of this research concern the integration of data acquired by image analysis with the managing and processing of big data coming from a wide kind of heterogeneous sources