Assessment of brain cancer atlas maps with multimodal imaging features.

BACKGROUND: Glioblastoma Multiforme (GBM) is a fast-growing and highly aggressive brain tumor that invades the nearby brain tissue and presents secondary nodular lesions across the whole brain but generally does not spread to distant organs. Without treatment, GBM can result in death in about 6 months. The challenges are known to depend on multiple factors: brain localization, resistance to conventional therapy, disrupted tumor blood supply inhibiting effective drug delivery, complications from peritumoral edema, intracranial hypertension, seizures, and neurotoxicity. MAIN TEXT: Imaging techniques are routinely used to obtain accurate detections of lesions that localize brain tumors. Especially magnetic resonance imaging (MRI) delivers multimodal images both before and after the administration of contrast, which results in displaying enhancement and describing physiological features as hemodynamic processes. This review considers one possible extension of the use of radiomics in GBM studies, one that recalibrates the analysis of targeted segmentations to the whole organ scale. After identifying critical areas of research, the focus is on illustrating the potential utility of an integrated approach with multimodal imaging, radiomic data processing and brain atlases as the main components. The templates associated with the outcome of straightforward analyses represent promising inference tools able to spatio-temporally inform on the GBM evolution while being generalizable also to other cancers. CONCLUSIONS: The focus on novel inference strategies applicable to complex cancer systems and based on building radiomic models from multimodal imaging data can be well supported by machine learning and other computational tools potentially able to translate suitably processed information into more accurate patient stratifications and evaluations of treatment efficacy

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

AI in Medical Imaging Informatics: Current Challenges and Future Directions

This paper reviews state-of-the-art research solutions across the spectrum of medical imaging informatics, discusses clinical translation, and provides future directions for advancing clinical practice. More specifically, it summarizes advances in medical imaging acquisition technologies for different modalities, highlighting the necessity for efficient medical data management strategies in the context of AI in big healthcare data analytics. It then provides a synopsis of contemporary and emerging algorithmic methods for disease classification and organ/ tissue segmentation, focusing on AI and deep learning architectures that have already become the de facto approach. The clinical benefits of in-silico modelling advances linked with evolving 3D reconstruction and visualization applications are further documented. Concluding, integrative analytics approaches driven by associate research branches highlighted in this study promise to revolutionize imaging informatics as known today across the healthcare continuum for both radiology and digital pathology applications. The latter, is projected to enable informed, more accurate diagnosis, timely prognosis, and effective treatment planning, underpinning precision medicine

Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas.

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naïve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmeanin the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmeanin the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmeanthreshold of 1201 × 10-6mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratiocut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratiothreshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study

Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell–cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations

Current State-of-the-Art of AI Methods Applied to MRI

Di Noia, C., Grist, J. T., Riemer, F., Lyasheva, M., Fabozzi, M., Castelli, M., Lodi, R., Tonon, C., Rundo, L., & Zaccagna, F. (2022). Predicting Survival in Patients with Brain Tumors: Current State-of-the-Art of AI Methods Applied to MRI. Diagnostics, 12(9), 1-16. [2125]. https://doi.org/10.3390/diagnostics12092125Given growing clinical needs, in recent years Artificial Intelligence (AI) techniques have increasingly been used to define the best approaches for survival assessment and prediction in patients with brain tumors. Advances in computational resources, and the collection of (mainly) public databases, have promoted this rapid development. This narrative review of the current state-of-the-art aimed to survey current applications of AI in predicting survival in patients with brain tumors, with a focus on Magnetic Resonance Imaging (MRI). An extensive search was performed on PubMed and Google Scholar using a Boolean research query based on MeSH terms and restricting the search to the period between 2012 and 2022. Fifty studies were selected, mainly based on Machine Learning (ML), Deep Learning (DL), radiomics-based methods, and methods that exploit traditional imaging techniques for survival assessment. In addition, we focused on two distinct tasks related to survival assessment: the first on the classification of subjects into survival classes (short and long-term or eventually short, mid and long-term) to stratify patients in distinct groups. The second focused on quantification, in days or months, of the individual survival interval. Our survey showed excellent state-of-the-art methods for the first, with accuracy up to ∼98%. The latter task appears to be the most challenging, but state-of-the-art techniques showed promising results, albeit with limitations, with C-Index up to ∼0.91. In conclusion, according to the specific task, the available computational methods perform differently, and the choice of the best one to use is non-univocal and dependent on many aspects. Unequivocally, the use of features derived from quantitative imaging has been shown to be advantageous for AI applications, including survival prediction. This evidence from the literature motivates further research in the field of AI-powered methods for survival prediction in patients with brain tumors, in particular, using the wealth of information provided by quantitative MRI techniques.publishersversionpublishe

Radiogenomics Framework for Associating Medical Image Features with Tumour Genetic Characteristics

Significant progress has been made in the understanding of human cancers at the molecular genetics level and it is providing new insights into their underlying pathophysiology. This progress has enabled the subclassification of the disease and the development of targeted therapies that address specific biological pathways. However, obtaining genetic information remains invasive and costly. Medical imaging is a non-invasive technique that captures important visual characteristics (i.e. image features) of abnormalities and plays an important role in routine clinical practice. Advancements in computerised medical image analysis have enabled quantitative approaches to extract image features that can reflect tumour genetic characteristics, leading to the emergence of ‘radiogenomics’. Radiogenomics investigates the relationships between medical imaging features and tumour molecular characteristics, and enables the derivation of imaging surrogates (radiogenomics features) to genetic biomarkers that can provide alternative approaches to non-invasive and accurate cancer diagnosis. This thesis presents a new framework that combines several novel methods for radiogenomics analysis that associates medical image features with tumour genetic characteristics, with the main objectives being: i) a comprehensive characterisation of tumour image features that reflect underlying genetic information; ii) a method that identifies radiogenomics features encoding common pathophysiological information across different diseases, overcoming the dependence on large annotated datasets; and iii) a method that quantifies radiogenomics features from multi-modal imaging data and accounts for unique information encoded in tumour heterogeneity sub-regions. The present radiogenomics methods advance radiogenomics analysis and contribute to improving research in computerised medical image analysis