Automatic detection and classification of nasopharyngeal carcinoma on PET/CT with support vector machine

Purpose: Positron emission tomography/computed tomography (PET/CT) has established values for imaging of head and neck cancers, including the nasopharyngeal carcinoma (NPC), utilizing both morphologic and functional information. In this paper, we introduce a computerized system for automatic detection of NPC, targeting both the primary tumor and regional nodal metastasis, on PET/CT. Methods: Candidate lesions were extracted based on the features from both PET and CT images and a priori knowledge of anatomical features and subsequently classified by a support vector machine algorithm. The system was validated with 25 PET/CT examinations from 10 patients suffering from NPC. Lesions manually contoured by experienced radiologists were used as the gold standard. Results: Results showed that the system successfully identified all 53 hypermetabolic lesions larger than 1 cm in size and excluded normal physiological uptake in brown fat, muscles, bone marrow, brain, and salivary glands. Conclusion: The system combined both imaging features and a priori clinical knowledge for classification between pathological and physiological uptake. Preliminary results showed that the system was highly accurate and promising for adoption in clinical use. © The Author(s) 2011.published_or_final_versionSpringer Open Choice, 25 May 201

Recent Applications of Artificial Intelligence in Radiotherapy: Where We Are and Beyond

In recent decades, artificial intelligence (AI) tools have been applied in many medical fields, opening the possibility of finding novel solutions for managing very complex and multifactorial problems, such as those commonly encountered in radiotherapy (RT). We conducted a PubMed and Scopus search to identify the AI application field in RT limited to the last four years. In total, 1824 original papers were identified, and 921 were analyzed by considering the phase of the RT workflow according to the applied AI approaches. AI permits the processing of large quantities of information, data, and images stored in RT oncology information systems, a process that is not manageable for individuals or groups. AI allows the iterative application of complex tasks in large datasets (e.g., delineating normal tissues or finding optimal planning solutions) and might support the entire community working in the various sectors of RT, as summarized in this overview. AI-based tools are now on the roadmap for RT and have been applied to the entire workflow, mainly for segmentation, the generation of synthetic images, and outcome prediction. Several concerns were raised, including the need for harmonization while overcoming ethical, legal, and skill barriers

Prior Guided Deep Difference Meta-Learner for Fast Adaptation to Stylized Segmentation

When a pre-trained general auto-segmentation model is deployed at a new institution, a support framework in the proposed Prior-guided DDL network will learn the systematic difference between the model predictions and the final contours revised and approved by clinicians for an initial group of patients. The learned style feature differences are concatenated with the new patients (query) features and then decoded to get the style-adapted segmentations. The model is independent of practice styles and anatomical structures. It meta-learns with simulated style differences and does not need to be exposed to any real clinical stylized structures during training. Once trained on the simulated data, it can be deployed for clinical use to adapt to new practice styles and new anatomical structures without further training. To show the proof of concept, we tested the Prior-guided DDL network on six different practice style variations for three different anatomical structures. Pre-trained segmentation models were adapted from post-operative clinical target volume (CTV) segmentation to segment CTVstyle1, CTVstyle2, and CTVstyle3, from parotid gland segmentation to segment Parotidsuperficial, and from rectum segmentation to segment Rectumsuperior and Rectumposterior. The mode performance was quantified with Dice Similarity Coefficient (DSC). With adaptation based on only the first three patients, the average DSCs were improved from 78.6, 71.9, 63.0, 52.2, 46.3 and 69.6 to 84.4, 77.8, 73.0, 77.8, 70.5, 68.1, for CTVstyle1, CTVstyle2, and CTVstyle3, Parotidsuperficial, Rectumsuperior, and Rectumposterior, respectively, showing the great potential of the Priorguided DDL network for a fast and effortless adaptation to new practice style

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline for Oropharyngeal Cancer Radiotherapy Treatment Guidance

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information coupled to artificial intelligence (AI) approaches could improve clinical decision support for OPC by providing immediately actionable clinical rationale for adaptive RT planning. If tumors could be reproducibly segmented, rapid response could be classified, and prognosis could be reliably determined, overall patient outcomes would be optimized to improve the therapeutic index as a function of more risk-adapted RT volumes. Consequently, there is an unmet need for automated and reproducible imaging which can simultaneously segment tumors and provide predictive value for actionable RT adaptation. This dissertation primarily seeks to explore and optimize image processing, tumor segmentation, and patient outcomes in OPC through a combination of advanced imaging techniques and AI algorithms. In the first specific aim of this dissertation, we develop and evaluate mpMRI pre-processing techniques for use in downstream segmentation, response prediction, and outcome prediction pipelines. Various MRI intensity standardization and registration approaches were systematically compared and benchmarked. Moreover, synthetic image algorithms were developed to decrease MRI scan time in an effort to optimize our AI pipelines. We demonstrated that proper intensity standardization and image registration can improve mpMRI quality for use in AI algorithms, and developed a novel method to decrease mpMRI acquisition time. Subsequently, in the second specific aim of this dissertation, we investigated underlying questions regarding the implementation of RT-related auto-segmentation. Firstly, we quantified interobserver variability for an unprecedented large number of observers for various radiotherapy structures in several disease sites (with a particular emphasis on OPC) using a novel crowdsourcing platform. We then trained an AI algorithm on a series of extant matched mpMRI datasets to segment OPC primary tumors. Moreover, we validated and compared our best model\u27s performance to clinical expert observers. We demonstrated that AI-based mpMRI OPC tumor auto-segmentation offers decreased variability and comparable accuracy to clinical experts, and certain mpMRI input channel combinations could further improve performance. Finally, in the third specific aim of this dissertation, we predicted OPC primary tumor mid-therapy (rapid) treatment response and prognostic outcomes. Using co-registered pre-therapy and mid-therapy primary tumor manual segmentations of OPC patients, we generated and characterized treatment sensitive and treatment resistant pre-RT sub-volumes. These sub-volumes were used to train an AI algorithm to predict individual voxel-wise treatment resistance. Additionally, we developed an AI algorithm to predict OPC patient progression free survival using pre-therapy imaging from an international data science competition (ranking 1st place), and then translated these approaches to mpMRI data. We demonstrated AI models could be used to predict rapid response and prognostic outcomes using pre-therapy imaging, which could help guide treatment adaptation, though further work is needed. In summary, the completion of these aims facilitates the development of an image-guided fully automated OPC clinical decision support tool. The resultant deliverables from this project will positively impact patients by enabling optimized therapeutic interventions in OPC. Future work should consider investigating additional imaging timepoints, imaging modalities, uncertainty quantification, perceptual and ethical considerations, and prospective studies for eventual clinical implementation. A dynamic version of this dissertation is publicly available and assigned a digital object identifier through Figshare (doi: 10.6084/m9.figshare.22141871)

State of the Art in Artificial Intelligence and Radiomics in Hepatocellular Carcinoma

The most common liver malignancy is hepatocellular carcinoma (HCC), which is also associated with high mortality. Often HCC develops in a chronic liver disease setting, and early diagnosis as well as accurate screening of high-risk patients is crucial for appropriate and effective management of these patients. While imaging characteristics of HCC are well-defined in the diagnostic phase, challenging cases still occur, and current prognostic and predictive models are limited in their accuracy. Radiomics and machine learning (ML) offer new tools to address these issues and may lead to scientific breakthroughs with the potential to impact clinical practice and improve patient outcomes. In this review, we will present an overview of these technologies in the setting of HCC imaging across different modalities and a range of applications. These include lesion segmentation, diagnosis, prognostic modeling and prediction of treatment response. Finally, limitations preventing clinical application of radiomics and ML at the present time are discussed, together with necessary future developments to bring the field forward and outside of a purely academic endeavor

Artificial Intelligence-based methods in head and neck cancer diagnosis : an overview

Background This paper reviews recent literature employing Artificial Intelligence/Machine Learning (AI/ML) methods for diagnostic evaluation of head and neck cancers (HNC) using automated image analysis. Methods Electronic database searches using MEDLINE via OVID, EMBASE and Google Scholar were conducted to retrieve articles using AI/ML for diagnostic evaluation of HNC (2009–2020). No restrictions were placed on the AI/ML method or imaging modality used. Results In total, 32 articles were identified. HNC sites included oral cavity (n = 16), nasopharynx (n = 3), oropharynx (n = 3), larynx (n = 2), salivary glands (n = 2), sinonasal (n = 1) and in five studies multiple sites were studied. Imaging modalities included histological (n = 9), radiological (n = 8), hyperspectral (n = 6), endoscopic/clinical (n = 5), infrared thermal (n = 1) and optical (n = 1). Clinicopathologic/genomic data were used in two studies. Traditional ML methods were employed in 22 studies (69%), deep learning (DL) in eight studies (25%) and a combination of these methods in two studies (6%). Conclusions There is an increasing volume of studies exploring the role of AI/ML to aid HNC detection using a range of imaging modalities. These methods can achieve high degrees of accuracy that can exceed the abilities of human judgement in making data predictions. Large-scale multi-centric prospective studies are required to aid deployment into clinical practice

Evaluering av maskinlæringsmetoder for automatisk tumorsegmentering

The definition of target volumes and organs at risk (OARs) is a critical part of radiotherapy planning. In routine practice, this is typically done manually by clinical experts who contour the structures in medical images prior to dosimetric planning. This is a time-consuming and labor-intensive task. Moreover, manual contouring is inherently a subjective task and substantial contour variability can occur, potentially impacting on radiotherapy treatment and image-derived biomarkers. Automatic segmentation (auto-segmentation) of target volumes and OARs has the potential to save time and resources while reducing contouring variability. Recently, auto-segmentation of OARs using machine learning methods has been integrated into the clinical workflow by several institutions and such tools have been made commercially available by major vendors. The use of machine learning methods for auto-segmentation of target volumes including the gross tumor volume (GTV) is less mature at present but is the focus of extensive ongoing research. The primary aim of this thesis was to investigate the use of machine learning methods for auto-segmentation of the GTV in medical images. Manual GTV contours constituted the ground truth in the analyses. Volumetric overlap and distance-based metrics were used to quantify auto-segmentation performance. Four different image datasets were evaluated. The first dataset, analyzed in papers I–II, consisted of positron emission tomography (PET) and contrast-enhanced computed tomography (ceCT) images of 197 patients with head and neck cancer (HNC). The ceCT images of this dataset were also included in paper IV. Two datasets were analyzed separately in paper III, namely (i) PET, ceCT, and low-dose CT (ldCT) images of 86 patients with anal cancer (AC), and (ii) PET, ceCT, ldCT, and T2 and diffusion-weighted (T2W and DW, respectively) MR images of a subset (n = 36) of the aforementioned AC patients. The last dataset consisted of ceCT images of 36 canine patients with HNC and was analyzed in paper IV. In paper I, three approaches to auto-segmentation of the GTV in patients with HNC were evaluated and compared, namely conventional PET thresholding, classical machine learning algorithms, and deep learning using a 2-dimensional (2D) U-Net convolutional neural network (CNN). For the latter two approaches the effect of imaging modality on auto-segmentation performance was also assessed. Deep learning based on multimodality PET/ceCT image input resulted in superior agreement with the manual ground truth contours, as quantified by geometric overlap and distance-based performance evaluation metrics calculated on a per patient basis. Moreover, only deep learning provided adequate performance for segmentation based solely on ceCT images. For segmentation based on PET-only, all three approaches provided adequate segmentation performance, though deep learning ranked first, followed by classical machine learning, and PET thresholding. In paper II, deep learning-based auto-segmentation of the GTV in patients with HNC using a 2D U-Net architecture was evaluated more thoroughly by introducing new structure-based performance evaluation metrics and including qualitative expert evaluation of the resulting auto-segmentation quality. As in paper I, multimodal PET/ceCT image input provided superior segmentation performance, compared to the single modality CNN models. The structure-based metrics showed quantitatively that the PET signal was vital for the sensitivity of the CNN models, as the superior PET/ceCT-based model identified 86 % of all malignant GTV structures whereas the ceCT-based model only identified 53 % of these structures. Furthermore, the majority of the qualitatively evaluated auto-segmentations (~ 90 %) generated by the best PET/ceCT-based CNN were given a quality score corresponding to substantial clinical value. Based on papers I and II, deep learning with multimodality PET/ceCT image input would be the recommended approach for auto-segmentation of the GTV in human patients with HNC. In paper III, deep learning-based auto-segmentation of the GTV in patients with AC was evaluated for the first time, using a 2D U-Net architecture. Furthermore, an extensive comparison of the impact of different single modality and multimodality combinations of PET, ceCT, ldCT, T2W, and/or DW image input on quantitative auto-segmentation performance was conducted. For both the 86-patient and 36-patient datasets, the models based on PET/ceCT provided the highest mean overlap with the manual ground truth contours. For this task, however, comparable auto-segmentation quality was obtained for solely ceCT-based CNN models. The CNN model based solely on T2W images also obtained acceptable auto-segmentation performance and was ranked as the second-best single modality model for the 36-patient dataset. These results indicate that deep learning could prove a versatile future tool for auto-segmentation of the GTV in patients with AC. Paper IV investigated for the first time the applicability of deep learning-based auto-segmentation of the GTV in canine patients with HNC, using a 3-dimensional (3D) U-Net architecture and ceCT image input. A transfer learning approach where CNN models were pre-trained on the human HNC data and subsequently fine-tuned on canine data was compared to training models from scratch on canine data. These two approaches resulted in similar auto-segmentation performances, which on average was comparable to the overlap metrics obtained for ceCT-based auto-segmentation in human HNC patients. Auto-segmentation in canine HNC patients appeared particularly promising for nasal cavity tumors, as the average overlap with manual contours was 25 % higher for this subgroup, compared to the average for all included tumor sites. In conclusion, deep learning with CNNs provided high-quality GTV autosegmentations for all datasets included in this thesis. In all cases, the best-performing deep learning models resulted in an average overlap with manual contours which was comparable to the reported interobserver agreements between human experts performing manual GTV contouring for the given cancer type and imaging modality. Based on these findings, further investigation of deep learning-based auto-segmentation of the GTV in the given diagnoses would be highly warranted.Definisjon av målvolum og risikoorganer er en kritisk del av planleggingen av strålebehandling. I praksis gjøres dette vanligvis manuelt av kliniske eksperter som tegner inn strukturenes konturer i medisinske bilder før dosimetrisk planlegging. Dette er en tids- og arbeidskrevende oppgave. Manuell inntegning er også subjektiv, og betydelig variasjon i inntegnede konturer kan forekomme. Slik variasjon kan potensielt påvirke strålebehandlingen og bildebaserte biomarkører. Automatisk segmentering (auto-segmentering) av målvolum og risikoorganer kan potensielt spare tid og ressurser samtidig som konturvariasjonen reduseres. Autosegmentering av risikoorganer ved hjelp av maskinlæringsmetoder har nylig blitt implementert som del av den kliniske arbeidsflyten ved flere helseinstitusjoner, og slike verktøy er kommersielt tilgjengelige hos store leverandører av medisinsk teknologi. Auto-segmentering av målvolum inkludert tumorvolumet gross tumor volume (GTV) ved hjelp av maskinlæringsmetoder er per i dag mindre teknologisk modent, men dette området er fokus for omfattende pågående forskning. Hovedmålet med denne avhandlingen var å undersøke bruken av maskinlæringsmetoder for auto-segmentering av GTV i medisinske bilder. Manuelle GTVinntegninger utgjorde grunnsannheten (the ground truth) i analysene. Mål på volumetrisk overlapp og avstand mellom sanne og predikerte konturer ble brukt til å kvantifisere kvaliteten til de automatisk genererte GTV-konturene. Fire forskjellige bildedatasett ble evaluert. Det første datasettet, analysert i artikkel I–II, bestod av positronemisjonstomografi (PET) og kontrastforsterkede computertomografi (ceCT) bilder av 197 pasienter med hode/halskreft. ceCT-bildene i dette datasettet ble også inkludert i artikkel IV. To datasett ble analysert separat i artikkel III, nemlig (i) PET, ceCT og lavdose CT (ldCT) bilder av 86 pasienter med analkreft, og (ii) PET, ceCT, ldCT og T2- og diffusjonsvektet (henholdsvis T2W og DW) MR-bilder av en undergruppe (n = 36) av de ovennevnte analkreftpasientene. Det siste datasettet, som bestod av ceCT-bilder av 36 hunder med hode/halskreft, ble analysert i artikkel IV

Potentials and caveats of AI in Hybrid Imaging

State-of-the-art patient management frequently mandates the investigation of both anatomy and physiology of the patients. Hybrid imaging modalities such as the PET/MRI, PET/CT and SPECT/CT have the ability to provide both structural and functional information of the investigated tissues in a single examination. With the introduction of such advanced hardware fusion, new problems arise such as the exceedingly large amount of multi-modality data that requires novel approaches of how to extract a maximum of clinical information from large sets of multi-dimensional imaging data. Artificial intelligence (AI) has emerged as one of the leading technologies that has shown promise in facilitating highly integrative analysis of multi-parametric data. Specifically, the usefulness of AI algorithms in the medical imaging field has been heavily investigated in the realms of (1) image acquisition and reconstruction, (2) post-processing and (3) data mining and modelling. Here, we aim to provide an overview of the challenges encountered in hybrid imaging and discuss how AI algorithms can facilitate potential solutions. In addition, we highlight the pitfalls and challenges in using advanced AI algorithms in the context of hybrid imaging and provide suggestions for building robust AI solutions that enable reproducible and transparent research