Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.

Purpose This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region. Methods Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size. Results VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10 −3 mm 2 /s vs. 0.98 ± 0.38 × 10 −3 mm 2 /s, respectively; p = 0.18). Conclusion This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future. Key Points • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale. Electronic supplementary material The online version of this article (10.1007/s00330-019-6011-8) contains supplementary material, w...

ObjectiveMonitoring biomarkers using machine learning (ML) may determine glioblastoma treatment response. We systematically reviewed quality and performance accuracy of recently published studies.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Diagnostic Test Accuracy, we extracted articles from MEDLINE, EMBASE and Cochrane Register between 09/2018–01/2021. Included study participants were adults with glioblastoma having undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide), and follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics, the target condition). Using Quality Assessment of Diagnostic Accuracy Studies Two/Checklist for Artificial Intelligence in Medical Imaging, we assessed bias risk and applicability concerns. We determined test set performance accuracy (sensitivity, specificity, precision, F1-score, balanced accuracy). We used a bivariate random-effect model to determine pooled sensitivity, specificity, area-under the receiver operator characteristic curve (ROC-AUC). Pooled measures of balanced accuracy, positive/negative likelihood ratios (PLR/NLR) and diagnostic odds ratio (DOR) were calculated. PROSPERO registered (CRD42021261965).ResultsEighteen studies were included (1335/384 patients for training/testing respectively). Small patient numbers, high bias risk, applicability concerns (particularly confounding in reference standard and patient selection) and low level of evidence, allow limited conclusions from studies. Ten studies (10/18, 56%) included in meta-analysis gave 0.769 (0.649-0.858) sensitivity [pooled (95% CI)]; 0.648 (0.749-0.532) specificity; 0.706 (0.623-0.779) balanced accuracy; 2.220 (1.560-3.140) PLR; 0.366 (0.213-0.572) NLR; 6.670 (2.800-13.500) DOR; 0.765 ROC-AUC.ConclusionML models using MRI features to distinguish between progression and mimics appear to demonstrate good diagnostic performance. However, study quality and design require improvement.

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