[Li-Fraumeni syndrome]. / Li-Fraumeni-Syndrom.

BACKGROUND: The autosomal dominant inherited Li-Fraumeni syndrome (LFS) increases the lifetime risk of developing a malignancy to almost 100%. Although breast cancer, central nervous system (CNS) tumors and sarcomas are particularly common, tumors can ultimately occur almost anywhere in the body. As causal therapy is not available, the primary focus for improving the prognosis is early cancer detection. To this end, current cancer surveillance recommendations include a series of examinations including regular imaging beginning at birth. CHALLENGES IN IMAGING IN LFS: Due to the wide range of tumor entities that can occur in individuals affected by LFS, a sensitive detection requires imaging of various tissue contrasts; however, because life-long screening is potentially initiated at a young age, this requirement for comprehensiveness must be balanced against the presumed high psychological burden associated with frequent or invasive examinations. As radiation exposure may lead to an increased (secondary) tumor risk, computed tomography (CT) and X­ray examinations should be avoided as far as possible. CURRENT STATUS AND PERSPECTIVES: Because annual whole-body magnetic resonance imaging (MRI) has no radiation exposure and yet a high sensitivity for many tumors, it forms the basis of the recommended imaging; however, due to the rarity of the syndrome, expertise is sometimes lacking and whole-body MRI examinations are performed heterogeneously and sometimes with limited diagnostic quality. Optimization and standardization of MRI protocols should therefore be pursued. In addition, the need for an intravenously administered contrast agent has not been conclusively clarified despite its high relevance.

Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale.

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation-perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial CTEPH diagnosis Europe - MRI (CHANGE-MRI, ClinicalTrials.gov identifier NCT02791282) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6-12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH.

Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi-ethnic study of atherosclerosis COPD study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Identification of imaging biomarkers for phenotyping is necessary for future treatment and therapy monitoring. However, translation of visual analytic pipelines into clinics or their use in large-scale studies is significantly slowed by time-consuming postprocessing steps. PURPOSE: To implement an automated tool chain for regional quantification of pulmonary microvascular blood flow in order to reduce analysis time and user variability. STUDY TYPE: Prospective. POPULATION: In all, 90 MRI scans of 63 patients, of which 31 had a COPD with a mean Global Initiative for Chronic Obstructive Lung Disease status of 1.9 ± 0.64 (µ ± σ). FIELD STRENGTH/SEQUENCE: 1.5T dynamic gadolinium-enhanced MRI measurement using 4D dynamic contrast material-enhanced (DCE) time-resolved angiography acquired in a single breath-hold in inspiration. [Correction added on August 20, 2019, after first online publication: The field strength in the preceding sentence was corrected.] ASSESSMENT: We built a 3D convolutional neural network for semantic segmentation using 29 manually segmented perfusion maps. All five lobes of the lung are denoted, including the middle lobe. Evaluation was performed on 61 independent cases from two sites of the Multi-Ethnic Study of Arteriosclerosis (MESA)-COPD study. We publish our implementation of a model-free deconvolution filter according to Sourbron et al for 4D DCE MRI scans as open source. STATISTICAL TEST: Cross-validation 29/61 (# training / # testing), intraclass correlation coefficient (ICC), Spearman ρ, Pearson r, Sørensen-Dice coefficient, and overlap. RESULTS: Segmentations and derived clinical parameters were processed in ~90 seconds per case on a Xeon E5-2637v4 workstation with Tesla P40 GPUs. Clinical parameters and predicted segmentations exhibit high concordance with the ground truth regarding median perfusion for all lobes with an ICC of 0.99 and a Sørensen-Dice coefficient of 93.4 ± 2.8 (µ ± σ). DATA CONCLUSION: We present a robust end-to-end pipeline that allows for the extraction of perfusion-based biomarkers for all lung lobes in 4D DCE MRI scans by combining model-free deconvolution with deep learning. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:571-579.

Validation of Automated Perfusion-Weighted Phase-Resolved Functional Lung (PREFUL)-MRI in Patients With Pulmonary Diseases.

BACKGROUND: Perfusion-weighted (Qw) noncontrast-enhanced proton lung MRI is a promising technique for assessment of pulmonary perfusion, but still requires validation. PURPOSE: To improve perfusion-weighted phase-resolved functional lung (PREFUL)-MRI, to validate PREFUL with perfusion single photon emission computed tomography (SPECT) as a gold standard, and to compare PREFUL with dynamic contrast-enhanced (DCE)-MRI as a reference. STUDY TYPE: Retrospective. POPULATION: Twenty patients with chronic obstructive pulmonary disease (COPD), 14 patients with cystic fibrosis (CF), and 21 patients with chronic thromboembolic pulmonary hypertension (CTEPH) were included. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI, a spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories sequence were used at 1.5T. ASSESSMENT: PREFUL-MRI coronal slices were acquired in free-breathing. DCE-MRI was performed in breath-hold with injection of 0.03 mmol/kg bodyweight of gadoteric acid at a rate of 4 cc/s. Perfusion SPECT images were obtained for six CTEPH patients. Images were coregistered. An algorithm to define the appropriate PREFUL perfusion phase was developed using perfusion SPECT data. Perfusion defect percentages (QDP) and Qw-values were calculated for all methods. For PREFUL quantitative perfusion values (PREFULQ ) and for DCE pulmonary blood flow (PBF) was calculated. STATISTICAL TESTS: Obtained parameters were assessed using Pearson correlation and Bland-Altman analysis. RESULTS: Qw-SPECT correlated with Qw-DCE (r = 0.50, P < 0.01) and Qw-PREFUL (r = 0.47, P < 0.01). Spatial overlap of QDP maps showed an agreement ≥67.7% comparing SPECT and DCE, ≥64.1% for SPECT and PREFUL, and ≥60.2% comparing DCE and PREFUL. Significant correlations of Qw-PREFUL and Qw-DCE were found (COPD: r = 0.79, P < 0.01; CF: r = 0.77, P < 0.01; CTEPH: r = 0.73, P < 0.01). PREFULQ /PBF correlations were similar/lower (CF, CTEPH: P > 0.12; COPD: P < 0.01) compared to Qw-PREFUL/DCE correlations. PREFULQ -values were higher/similar compared to PBF-values (COPD, CF: P < 0.01; CTEPH: P = 0.026). DATA CONCLUSION: The automated PREFUL algorithm may allow for noncontrast-enhanced pulmonary perfusion assessment in COPD, CF, and CTEPH patients comparable to DCE-MRI. Level of Evidence 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:103-114.