Linear multi-scale modeling of diffusion MRI data: A framework for characterization of oriented structures across length scales.

Diffusion-weighted magnetic resonance imaging (DW-MRI) has evolved to provide increasingly sophisticated investigations of the human brain's structural connectome in vivo. Restriction spectrum imaging (RSI) is a method that reconstructs the orientation distribution of diffusion within tissues over a range of length scales. In its original formulation, RSI represented the signal as consisting of a spectrum of Gaussian diffusion response functions. Recent technological advances have enabled the use of ultra-high b-values on human MRI scanners, providing higher sensitivity to intracellular water diffusion in the living human brain. To capture the complex diffusion time dependence of the signal within restricted water compartments, we expand upon the RSI approach to represent restricted water compartments with non-Gaussian response functions, in an extended analysis framework called linear multi-scale modeling (LMM). The LMM approach is designed to resolve length scale and orientation-specific information with greater specificity to tissue microstructure in the restricted and hindered compartments, while retaining the advantages of the RSI approach in its implementation as a linear inverse problem. Using multi-shell, multi-diffusion time DW-MRI data acquired with a state-of-the-art 3 T MRI scanner equipped with 300 mT/m gradients, we demonstrate the ability of the LMM approach to distinguish different anatomical structures in the human brain and the potential to advance mapping of the human connectome through joint estimation of the fiber orientation distributions and compartment size characteristics.

End-to-end automated body composition analyses with integrated quality control for opportunistic assessment of sarcopenia in CT.

OBJECTIVES: To develop a pipeline for automated body composition analysis and skeletal muscle assessment with integrated quality control for large-scale application in opportunistic imaging. METHODS: First, a convolutional neural network for extraction of a single slice at the L3/L4 lumbar level was developed on CT scans of 240 patients applying the nnU-Net framework. Second, a 2D competitive dense fully convolutional U-Net for segmentation of visceral and subcutaneous adipose tissue (VAT, SAT), skeletal muscle (SM), and subsequent determination of fatty muscle fraction (FMF) was developed on single CT slices of 1143 patients. For both steps, automated quality control was integrated by a logistic regression model classifying the presence of L3/L4 and a linear regression model predicting the segmentation quality in terms of Dice score. To evaluate the performance of the entire pipeline end-to-end, body composition metrics, and FMF were compared to manual analyses including 364 patients from two centers. RESULTS: Excellent results were observed for slice extraction (z-deviation = 2.46 ± 6.20 mm) and segmentation (Dice score for SM = 0.95 ± 0.04, VAT = 0.98 ± 0.02, SAT = 0.97 ± 0.04) on the dual-center test set excluding cases with artifacts due to metallic implants. No data were excluded for end-to-end performance analyses. With a restrictive setting of the integrated segmentation quality control, 39 of 364 patients were excluded containing 8 cases with metallic implants. This setting ensured a high agreement between manual and fully automated analyses with mean relative area deviations of ΔSM = 3.3 ± 4.1%, ΔVAT = 3.0 ± 4.7%, ΔSAT = 2.7 ± 4.3%, and ΔFMF = 4.3 ± 4.4%. CONCLUSIONS: This study presents an end-to-end automated deep learning pipeline for large-scale opportunistic assessment of body composition metrics and sarcopenia biomarkers in clinical routine. KEY POINTS: • Body composition metrics and skeletal muscle quality can be opportunistically determined from routine abdominal CT scans. • A pipeline consisting of two convolutional neural networks allows an end-to-end automated analysis. • Machine-learning-based quality control ensures high agreement between manual and automatic analysis.

Radiomics workflow definition & challenges - German priority program 2177 consensus statement on clinically applied radiomics.

OBJECTIVES: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation. MATERIALS AND METHODS: The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges. RESULTS: Workflow definitions from 22 publications (published 2012-2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts "agree" or "strongly agree"). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts' perspective the ten most important challenges in radiomics workflows. CONCLUSION: To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized. CRITICAL RELEVANCE STATEMENT: Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics. KEY POINTS: Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community.

Influence of Image Processing on Radiomic Features From Magnetic Resonance Imaging.

OBJECTIVE: Before implementing radiomics in routine clinical practice, comprehensive knowledge about the repeatability and reproducibility of radiomic features is required. The aim of this study was to systematically investigate the influence of image processing parameters on radiomic features from magnetic resonance imaging (MRI) in terms of feature values as well as test-retest repeatability. MATERIALS AND METHODS: Utilizing a phantom consisting of 4 onions, 4 limes, 4 kiwifruits, and 4 apples, we acquired a test-retest dataset featuring 3 of the most commonly used MRI sequences on a 3 T scanner, namely, a T1-weighted, a T2-weighted, and a fluid-attenuated inversion recovery sequence, each at high and low resolution. After semiautomatic image segmentation, image processing with systematic variation of image processing parameters was performed, including spatial resampling, intensity discretization, and intensity rescaling. For each respective image processing setting, a total of 45 radiomic features were extracted, corresponding to the following 7 matrices/feature classes: conventional indices, histogram matrix, shape matrix, gray-level zone length matrix, gray-level run length matrix, neighboring gray-level dependence matrix, and gray-level cooccurrence matrix. Systematic differences of individual features between different resampling steps were assessed using 1-way analysis of variance with Tukey-type post hoc comparisons to adjust for multiple testing. Test-retest repeatability of radiomic features was measured using the concordance correlation coefficient, dynamic range, and intraclass correlation coefficient. RESULTS: Image processing influenced radiological feature values. Regardless of the acquired sequence and feature class, significant differences ( P < 0.05) in feature values were found when the size of the resampled voxels was too large, that is, bigger than 3 mm. Almost all higher-order features depended strongly on intensity discretization. The effects of intensity rescaling were negligible except for some features derived from T1-weighted sequences. For all sequences, the percentage of repeatable features (concordance correlation coefficient and dynamic range ≥ 0.9) varied considerably depending on the image processing settings. The optimal image processing setting to achieve the highest percentage of stable features varied per sequence. Irrespective of image processing, the fluid-attenuated inversion recovery sequence in high-resolution overall yielded the highest number of stable features in comparison with the other sequences (89% vs 64%-78% for the respective optimal image processing settings). Across all sequences, the most repeatable features were generally obtained for a spatial resampling close to the originally acquired voxel size and an intensity discretization to at least 32 bins. CONCLUSION: Variation of image processing parameters has a significant impact on the values of radiomic features as well as their repeatability. Furthermore, the optimal image processing parameters differ for each MRI sequence. Therefore, it is recommended that these processing parameters be determined in corresponding test-retest scans before clinical application. Extensive repeatability, reproducibility, and validation studies as well as standardization are required before quantitative image analysis and radiomics can be reliably translated into routine clinical care.

Are We There Yet? The Value of Deep Learning in a Multicenter Setting for Response Prediction of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy.

This retrospective study aims to evaluate the generalizability of a promising state-of-the-art multitask deep learning (DL) model for predicting the response of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (nCRT) using a multicenter dataset. To this end, we retrained and validated a Siamese network with two U-Nets joined at multiple layers using pre- and post-therapeutic T2-weighted (T2w), diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps of 83 LARC patients acquired under study conditions at four different medical centers. To assess the predictive performance of the model, the trained network was then applied to an external clinical routine dataset of 46 LARC patients imaged without study conditions. The training and test datasets differed significantly in terms of their composition, e.g., T-/N-staging, the time interval between initial staging/nCRT/re-staging and surgery, as well as with respect to acquisition parameters, such as resolution, echo/repetition time, flip angle and field strength. We found that even after dedicated data pre-processing, the predictive performance dropped significantly in this multicenter setting compared to a previously published single- or two-center setting. Testing the network on the external clinical routine dataset yielded an area under the receiver operating characteristic curve of 0.54 (95% confidence interval [CI]: 0.41, 0.65), when using only pre- and post-therapeutic T2w images as input, and 0.60 (95% CI: 0.48, 0.71), when using the combination of pre- and post-therapeutic T2w, DW images, and ADC maps as input. Our study highlights the importance of data quality and harmonization in clinical trials using machine learning. Only in a joint, cross-center effort, involving a multidisciplinary team can we generate large enough curated and annotated datasets and develop the necessary pre-processing pipelines for data harmonization to successfully apply DL models clinically.

Technological Advances of Magnetic Resonance Imaging in Today's Health Care Environment.

Today's health care environment is shifting rapidly, driven by demographic change and high economic pressures on the system. Furthermore, modern precision medicine requires highly accurate and specific disease diagnostics in a short amount of time. Future imaging technology must adapt to these challenges.Demographic change necessitates scanner technologies tailored to the needs of an aging and increasingly multimorbid patient population. Accordingly, examination times have to be short enough that diagnostic images can be generated even for patients who can only lie in the scanner for a short time because of pain or with low breath-hold capacity.For economic reasons, the rate of nondiagnostic scans due to artifacts should be reduced as far as possible. As imaging plays an increasingly pivotal role in clinical-therapeutic decision making, magnetic resonance (MR) imaging facilities are confronted with an ever-growing number of patients, emphasizing the need for faster acquisitions while maintaining image quality.Lastly, modern precision medicine requires high and standardized image quality as well as quantifiable data in order to develop image-based biomarkers on which subsequent treatment management can rely.In recent decades, a variety of approaches have addressed the challenges of high throughput, demographic change, and precision medicine in MR imaging. These include field strength, gradient, coil and sequence development, as well as an increasing consideration of artificial intelligence. This article reviews state-of-the art MR technology and discusses future implementation from the perspective of what we know today.