Robustness of radiomic features in magnetic resonance imaging for patients with glioblastoma: Multi-center study

Background and purpose Radiomics offers great potential in improving diagnosis and treatment for patients with glioblastoma multiforme. However, in order to implement radiomics in clinical routine, the features used for prognostic modelling need to be stable. This comprises significant challenge in multi-center studies. The aim of this study was to evaluate the impact of different image normalization methods on MRI features robustness in multi-center study. Methods Radiomics stability was checked on magnetic resonance images of eleven patients. The images were acquired in two different hospitals using contrast-enhanced T1 sequences. The images were normalized using one of five investigated approaches including grey-level discretization, histogram matching and z-score. Then, radiomic features were extracted and features stability was evaluated using intra-class correlation coefficients. In the second part of the study, improvement in the prognostic performance of features was tested on 60 patients derived from publicly available dataset. Results Depending on the normalization scheme, the percentage of stable features varied from 3.4% to 8%. The histogram matching based on the tumor region showed the highest amount of the stable features (113/1404); while normalization using fixed bin size resulted in 48 stable features. The histogram matching also led to better prognostic value (median c-index increase of 0.065) comparing to non-normalized images. Conclusions MRI normalization plays an important role in radiomics. Appropriate normalization helps to select robust features, which can be used for prognostic modelling in multicenter studies. In our study, histogram matching based on tumor region improved both stability of radiomic features and their prognostic value

Radiomics analyses for outcome prediction in patients with locally advanced rectal cancer and glioblastoma multiforme using multimodal imaging data

Personalized treatment strategies for oncological patient management can improve outcomes of patient populations with heterogeneous treatment response. The implementation of such a concept requires the identification of biomarkers that can precisely predict treatment outcome. In the context of this thesis, we develop and validate biomarkers from multimodal imaging data for the outcome prediction after treatment in patients with locally advanced rectal cancer (LARC) and in patients with newly diagnosed glioblastoma multiforme (GBM), using conventional feature-based radiomics and deep-learning (DL) based radiomics. For LARC patients, we identify promising radiomics signatures combining computed tomography (CT) and T2-weighted (T2-w) magnetic resonance imaging (MRI) with clinical parameters to predict tumour response to neoadjuvant chemoradiotherapy (nCRT). Further, the analyses of externally available radiomics models for LARC reveal a lack of reproducibility and the need for standardization of the radiomics process. For patients with GBM, we use postoperative [11C] methionine positron emission tomography (MET-PET) and gadolinium-enhanced T1-w MRI for the detection of the residual tumour status and to prognosticate time-to-recurrence (TTR) and overall survival (OS). We show that DL models built on MET-PET have an improved diagnostic and prognostic value as compared to MRI

Medical Image Analytics (Radiomics) with Machine/Deeping Learning for Outcome Modeling in Radiation Oncology

Image-based quantitative analysis (radiomics) has gained great attention recently. Radiomics possesses promising potentials to be applied in the clinical practice of radiotherapy and to provide personalized healthcare for cancer patients. However, there are several challenges along the way that this thesis will attempt to address. Specifically, this thesis focuses on the investigation of repeatability and reproducibility of radiomics features, the development of new machine/deep learning models, and combining these for robust outcomes modeling and their applications in radiotherapy. Radiomics features suffer from robustness issues when applied to outcome modeling problems, especially in head and neck computed tomography (CT) images. These images tend to contain streak artifacts due to patients’ dental implants. To investigate the influence of artifacts for radiomics modeling performance, we firstly developed an automatic artifact detection algorithm using gradient-based hand-crafted features. Then, comparing the radiomics models trained on ‘clean’ and ‘contaminated’ datasets. The second project focused on using hand-crafted radiomics features and conventional machine learning methods for the prediction of overall response and progression-free survival for Y90 treated liver cancer patients. By identifying robust features and embedding prior knowledge in the engineered radiomics features and using bootstrapped LASSO to select robust features, we trained imaging and dose based models for the desired clinical endpoints, highlighting the complementary nature of this information in Y90 outcomes prediction. Combining hand-crafted and machine learnt features can take advantage of both expert domain knowledge and advanced data-driven approaches (e.g., deep learning). Thus, we proposed a new variational autoencoder network framework that modeled radiomics features, clinical factors, and raw CT images for the prediction of intrahepatic recurrence-free and overall survival for hepatocellular carcinoma (HCC) patients in this third project. The proposed approach was compared with widely used Cox proportional hazard model for survival analysis. Our proposed methods achieved significant improvement in terms of the prediction using the c-index metric highlighting the value of advanced modeling techniques in learning from limited and heterogeneous information in actuarial prediction of outcomes. Advances in stereotactic radiation therapy (SBRT) has led to excellent local tumor control with limited toxicities for HCC patients, but intrahepatic recurrence still remains prevalent. As an extension of the third project, we not only hope to predict the time to intrahepatic recurrence, but also the location where the tumor might recur. This will be clinically beneficial for better intervention and optimizing decision making during the process of radiotherapy treatment planning. To address this challenging task, firstly, we proposed an unsupervised registration neural network to register atlas CT to patient simulation CT and obtain the liver’s Couinaud segments for the entire patient cohort. Secondly, a new attention convolutional neural network has been applied to utilize multimodality images (CT, MR and 3D dose distribution) for the prediction of high-risk segments. The results showed much improved efficiency for obtaining segments compared with conventional registration methods and the prediction performance showed promising accuracy for anticipating the recurrence location as well. Overall, this thesis contributed new methods and techniques to improve the utilization of radiomics for personalized radiotherapy. These contributions included new algorithm for detecting artifacts, a joint model of dose with image heterogeneity, combining hand-crafted features with machine learnt features for actuarial radiomics modeling, and a novel approach for predicting location of treatment failure.PHDApplied PhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163092/1/liswei_1.pd

Radiomics in Lung Cancer from Basic to Advanced: Current Status and Future Directions

Copyright © 2020 The Korean Society of Radiology.Ideally, radiomics features and radiomics signatures can be used as imaging biomarkers for diagnosis, staging, prognosis, and prediction of tumor response. Thus, the number of published radiomics studies is increasing exponentially, leading to a myriad of new radiomics-based evidence for lung cancer. Consequently, it is challenging for radiologists to keep up with the development of radiomics features and their clinical applications. In this article, we review the basics to advanced radiomics in lung cancer to guide young researchers who are eager to start exploring radiomics investigations. In addition, we also include technical issues of radiomics, because knowledge of the technical aspects of radiomics supports a well-informed interpretation of the use of radiomics in lung cancer11Nsciescopuskc

The Role of Radiomics and AI Technologies in the Segmentation, Detection, and Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary hepatic neoplasm. Thanks to recent advances in computed tomography (CT) and magnetic resonance imaging (MRI), there is potential to improve detection, segmentation, discrimination from HCC mimics, and monitoring of therapeutic response. Radiomics, artificial intelligence (AI), and derived tools have already been applied in other areas of diagnostic imaging with promising results. In this review, we briefly discuss the current clinical applications of radiomics and AI in the detection, segmentation, and management of HCC. Moreover, we investigate their potential to reach a more accurate diagnosis of HCC and to guide proper treatment planning

Assessing Versatile Machine Learning Models for Glioma Radiogenomic Studies across Hospitals

Radiogenomics use non-invasively obtained imaging data, such as magnetic resonance imaging (MRI), to predict critical biomarkers of patients. Developing an accurate machine learning (ML) technique for MRI requires data from hundreds of patients, which cannot be gathered from any single local hospital. Hence, a model universally applicable to multiple cohorts/hospitals is required. We applied various ML and image pre-processing procedures on a glioma dataset from The Cancer Image Archive (TCIA, n = 159). The models that showed a high level of accuracy in predicting glioblastoma or WHO Grade II and III glioma using the TCIA dataset, were then tested for the data from the National Cancer Center Hospital, Japan (NCC, n = 166) whether they could maintain similar levels of high accuracy. Results: we confirmed that our ML procedure achieved a level of accuracy (AUROC = 0.904) comparable to that shown previously by the deep-learning methods using TCIA. However, when we directly applied the model to the NCC dataset, its AUROC dropped to 0.383. Introduction of standardization and dimension reduction procedures before classification without re-training improved the prediction accuracy obtained using NCC (0.804) without a loss in prediction accuracy for the TCIA dataset. Furthermore, we confirmed the same tendency in a model for IDH1/2 mutation prediction with standardization and application of dimension reduction that was also applicable to multiple hospitals. Our results demonstrated that overfitting may occur when an ML method providing the highest accuracy in a small training dataset is used for different heterogeneous data sets, and suggested a promising process for developing an ML method applicable to multiple cohort

Identifying the best machine learning algorithms for brain tumor segmentation, progression assessment, and overall survival prediction in the BRATS challenge

International Brain Tumor Segmentation (BraTS) challengeGliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.This work was supported in part by the 1) National Institute of Neurological Disorders and Stroke (NINDS) of the NIH R01 grant with award number R01-NS042645, 2) Informatics Technology for Cancer Research (ITCR) program of the NCI/NIH U24 grant with award number U24-CA189523, 3) Swiss Cancer League, under award number KFS-3979-08-2016, 4) Swiss National Science Foundation, under award number 169607.Article signat per 427 autors/es: Spyridon Bakas1,2,3,†,‡,∗ , Mauricio Reyes4,† , Andras Jakab5,†,‡ , Stefan Bauer4,6,169,† , Markus Rempfler9,65,127,† , Alessandro Crimi7,† , Russell Takeshi Shinohara1,8,† , Christoph Berger9,† , Sung Min Ha1,2,† , Martin Rozycki1,2,† , Marcel Prastawa10,† , Esther Alberts9,65,127,† , Jana Lipkova9,65,127,† , John Freymann11,12,‡ , Justin Kirby11,12,‡ , Michel Bilello1,2,‡ , Hassan M. Fathallah-Shaykh13,‡ , Roland Wiest4,6,‡ , Jan Kirschke126,‡ , Benedikt Wiestler126,‡ , Rivka Colen14,‡ , Aikaterini Kotrotsou14,‡ , Pamela Lamontagne15,‡ , Daniel Marcus16,17,‡ , Mikhail Milchenko16,17,‡ , Arash Nazeri17,‡ , Marc-Andr Weber18,‡ , Abhishek Mahajan19,‡ , Ujjwal Baid20,‡ , Elizabeth Gerstner123,124,‡ , Dongjin Kwon1,2,† , Gagan Acharya107, Manu Agarwal109, Mahbubul Alam33 , Alberto Albiol34, Antonio Albiol34, Francisco J. Albiol35, Varghese Alex107, Nigel Allinson143, Pedro H. A. Amorim159, Abhijit Amrutkar107, Ganesh Anand107, Simon Andermatt152, Tal Arbel92, Pablo Arbelaez134, Aaron Avery60, Muneeza Azmat62, Pranjal B.107, Wenjia Bai128, Subhashis Banerjee36,37, Bill Barth2 , Thomas Batchelder33, Kayhan Batmanghelich88, Enzo Battistella42,43 , Andrew Beers123,124, Mikhail Belyaev137, Martin Bendszus23, Eze Benson38, Jose Bernal40 , Halandur Nagaraja Bharath141, George Biros62, Sotirios Bisdas76, James Brown123,124, Mariano Cabezas40, Shilei Cao67, Jorge M. Cardoso76, Eric N Carver41, Adri Casamitjana138, Laura Silvana Castillo134, Marcel Cat138, Philippe Cattin152, Albert Cerigues ´ 40, Vinicius S. Chagas159 , Siddhartha Chandra42, Yi-Ju Chang45, Shiyu Chang156, Ken Chang123,124, Joseph Chazalon29 , Shengcong Chen25, Wei Chen46, Jefferson W Chen80, Zhaolin Chen130, Kun Cheng120, Ahana Roy Choudhury47, Roger Chylla60, Albert Clrigues40, Steven Colleman141, Ramiro German Rodriguez Colmeiro149,150,151, Marc Combalia138, Anthony Costa122, Xiaomeng Cui115, Zhenzhen Dai41, Lutao Dai50, Laura Alexandra Daza134, Eric Deutsch43, Changxing Ding25, Chao Dong65 , Shidu Dong155, Wojciech Dudzik71,72, Zach Eaton-Rosen76, Gary Egan130, Guilherme Escudero159, Tho Estienne42,43, Richard Everson87, Jonathan Fabrizio29, Yong Fan1,2 , Longwei Fang54,55, Xue Feng27, Enzo Ferrante128, Lucas Fidon42, Martin Fischer95, Andrew P. French38,39 , Naomi Fridman57, Huan Fu90, David Fuentes58, Yaozong Gao68, Evan Gates58, David Gering60 , Amir Gholami61, Willi Gierke95, Ben Glocker128, Mingming Gong88,89, Sandra Gonzlez-Vill40, T. Grosges151, Yuanfang Guan108, Sheng Guo64, Sudeep Gupta19, Woo-Sup Han63, Il Song Han63 , Konstantin Harmuth95, Huiguang He54,55,56, Aura Hernndez-Sabat100, Evelyn Herrmann102 , Naveen Himthani62, Winston Hsu111, Cheyu Hsu111, Xiaojun Hu64, Xiaobin Hu65, Yan Hu66, Yifan Hu117, Rui Hua68,69, Teng-Yi Huang45, Weilin Huang64, Sabine Van Huffel141, Quan Huo68, Vivek HV70, Khan M. Iftekharuddin33, Fabian Isensee22, Mobarakol Islam81,82, Aaron S. Jackson38 , Sachin R. Jambawalikar48, Andrew Jesson92, Weijian Jian119, Peter Jin61, V Jeya Maria Jose82,83 , Alain Jungo4 , Bernhard Kainz128, Konstantinos Kamnitsas128, Po-Yu Kao79, Ayush Karnawat129 , Thomas Kellermeier95, Adel Kermi74, Kurt Keutzer61, Mohamed Tarek Khadir75, Mahendra Khened107, Philipp Kickingereder23, Geena Kim135, Nik King60, Haley Knapp60, Urspeter Knecht4 , Lisa Kohli60, Deren Kong64, Xiangmao Kong115, Simon Koppers32, Avinash Kori107, Ganapathy Krishnamurthi107, Egor Krivov137, Piyush Kumar47, Kaisar Kushibar40, Dmitrii Lachinov84,85 , Tryphon Lambrou143, Joon Lee41, Chengen Lee111, Yuehchou Lee111, Matthew Chung Hai Lee128 , Szidonia Lefkovits96, Laszlo Lefkovits97, James Levitt62, Tengfei Li51, Hongwei Li65, Wenqi Li76,77 , Hongyang Li108, Xiaochuan Li110, Yuexiang Li133, Heng Li51, Zhenye Li146, Xiaoyu Li67, Zeju Li158 , XiaoGang Li162, Wenqi Li76,77, Zheng-Shen Lin45, Fengming Lin115, Pietro Lio153, Chang Liu41 , Boqiang Liu46, Xiang Liu67, Mingyuan Liu114, Ju Liu115,116, Luyan Liu112, Xavier Llado´ 40, Marc Moreno Lopez132, Pablo Ribalta Lorenzo72, Zhentai Lu53, Lin Luo31, Zhigang Luo162, Jun Ma73 , Kai Ma117, Thomas Mackie60, Anant Madabhushi129, Issam Mahmoudi74, Klaus H. Maier-Hein22 , Pradipta Maji36, CP Mammen161, Andreas Mang165, B. S. Manjunath79, Michal Marcinkiewicz71 , Steven McDonagh128, Stephen McKenna157, Richard McKinley6 , Miriam Mehl166, Sachin Mehta91 , Raghav Mehta92, Raphael Meier4,6 , Christoph Meinel95, Dorit Merhof32, Craig Meyer27,28, Robert Miller131, Sushmita Mitra36, Aliasgar Moiyadi19, David Molina-Garcia142, Miguel A.B. Monteiro105 , Grzegorz Mrukwa71,72, Andriy Myronenko21, Jakub Nalepa71,72, Thuyen Ngo79, Dong Nie113, Holly Ning131, Chen Niu67, Nicholas K Nuechterlein91, Eric Oermann122, Arlindo Oliveira105,106, Diego D. C. Oliveira159, Arnau Oliver40, Alexander F. I. Osman140, Yu-Nian Ou45, Sebastien Ourselin76 , Nikos Paragios42,44, Moo Sung Park121, Brad Paschke60, J. Gregory Pauloski58, Kamlesh Pawar130, Nick Pawlowski128, Linmin Pei33, Suting Peng46, Silvio M. Pereira159, Julian Perez-Beteta142, Victor M. Perez-Garcia142, Simon Pezold152, Bao Pham104, Ashish Phophalia136 , Gemma Piella101, G.N. Pillai109, Marie Piraud65, Maxim Pisov137, Anmol Popli109, Michael P. Pound38, Reza Pourreza131, Prateek Prasanna129, Vesna Pr?kovska99, Tony P. Pridmore38, Santi Puch99, lodie Puybareau29, Buyue Qian67, Xu Qiao46, Martin Rajchl128, Swapnil Rane19, Michael Rebsamen4 , Hongliang Ren82, Xuhua Ren112, Karthik Revanuru139, Mina Rezaei95, Oliver Rippel32, Luis Carlos Rivera134, Charlotte Robert43, Bruce Rosen123,124, Daniel Rueckert128 , Mohammed Safwan107, Mostafa Salem40, Joaquim Salvi40, Irina Sanchez138, Irina Snchez99 , Heitor M. Santos159, Emmett Sartor160, Dawid Schellingerhout59, Klaudius Scheufele166, Matthew R. Scott64, Artur A. Scussel159, Sara Sedlar139, Juan Pablo Serrano-Rubio86, N. Jon Shah130 , Nameetha Shah139, Mazhar Shaikh107, B. Uma Shankar36, Zeina Shboul33, Haipeng Shen50 , Dinggang Shen113, Linlin Shen133, Haocheng Shen157, Varun Shenoy61, Feng Shi68, Hyung Eun Shin121, Hai Shu52, Diana Sima141, Matthew Sinclair128, Orjan Smedby167, James M. Snyder41 , Mohammadreza Soltaninejad143, Guidong Song145, Mehul Soni107, Jean Stawiaski78, Shashank Subramanian62, Li Sun30, Roger Sun42,43, Jiawei Sun46, Kay Sun60, Yu Sun69, Guoxia Sun115 , Shuang Sun115, Yannick R Suter4 , Laszlo Szilagyi97, Sanjay Talbar20, Dacheng Tao26, Dacheng Tao90, Zhongzhao Teng154, Siddhesh Thakur20, Meenakshi H Thakur19, Sameer Tharakan62 , Pallavi Tiwari129, Guillaume Tochon29, Tuan Tran103, Yuhsiang M. Tsai111, Kuan-Lun Tseng111 , Tran Anh Tuan103, Vadim Turlapov85, Nicholas Tustison28, Maria Vakalopoulou42,43, Sergi Valverde40, Rami Vanguri48,49, Evgeny Vasiliev85, Jonathan Ventura132, Luis Vera142, Tom Vercauteren76,77, C. A. Verrastro149,150, Lasitha Vidyaratne33, Veronica Vilaplana138, Ajeet Vivekanandan60, Guotai Wang76,77, Qian Wang112, Chiatse J. Wang111, Weichung Wang111, Duo Wang153, Ruixuan Wang157, Yuanyuan Wang158, Chunliang Wang167, Guotai Wang76,77, Ning Wen41, Xin Wen67, Leon Weninger32, Wolfgang Wick24, Shaocheng Wu108, Qiang Wu115,116 , Yihong Wu144, Yong Xia66, Yanwu Xu88, Xiaowen Xu115, Peiyuan Xu117, Tsai-Ling Yang45 , Xiaoping Yang73, Hao-Yu Yang93,94, Junlin Yang93, Haojin Yang95, Guang Yang170, Hongdou Yao98, Xujiong Ye143, Changchang Yin67, Brett Young-Moxon60, Jinhua Yu158, Xiangyu Yue61 , Songtao Zhang30, Angela Zhang79, Kun Zhang89, Xuejie Zhang98, Lichi Zhang112, Xiaoyue Zhang118, Yazhuo Zhang145,146,147, Lei Zhang143, Jianguo Zhang157, Xiang Zhang162, Tianhao Zhang168, Sicheng Zhao61, Yu Zhao65, Xiaomei Zhao144,55, Liang Zhao163,164, Yefeng Zheng117 , Liming Zhong53, Chenhong Zhou25, Xiaobing Zhou98, Fan Zhou51, Hongtu Zhu51, Jin Zhu153, Ying Zhuge131, Weiwei Zong41, Jayashree Kalpathy-Cramer123,124,† , Keyvan Farahani12,†,‡ , Christos Davatzikos1,2,†,‡ , Koen van Leemput123,124,125,† , and Bjoern Menze9,65,127,†,∗Preprin

Differentiation of recurrent glioblastoma from radiation necrosis using diffusion radiomics with machine learning model development and external validation

The purpose of this study was to establish a high-performing radiomics strategy with machine learning from conventional and diffusion MRI to differentiate recurrent glioblastoma (GBM) from radiation necrosis (RN) after concurrent chemoradiotherapy (CCRT) or radiotherapy. Eighty-six patients with GBM were enrolled in the training set after they underwent CCRT or radiotherapy and presented with new or enlarging contrast enhancement within the radiation field on follow-up MRI. A diagnosis was established either pathologically or clinicoradiologically (63 recurrent GBM and 23 RN). Another 41 patients (23 recurrent GBM and 18 RN) from a different institution were enrolled in the test set. Conventional MRI sequences (T2-weighted and postcontrast T1-weighted images) and ADC were analyzed to extract 263 radiomic features. After feature selection, various machine learning models with oversampling methods were trained with combinations of MRI sequences and subsequently validated in the test set. In the independent test set, the model using ADC sequence showed the best diagnostic performance, with an AUC, accuracy, sensitivity, specificity of 0.80, 78%, 66.7%, and 87%, respectively. In conclusion, the radiomics models models using other MRI sequences showed AUCs ranging from 0.65 to 0.66 in the test set. The diffusion radiomics may be helpful in differentiating recurrent GBM from RN..ope