Time-efficient combined morphologic and quantitative joint MRI based on clinical image contrasts -- An exploratory in-situ study of standardized cartilage defects

OBJECTIVES: Quantitative MRI techniques such as T2 and T1$\rho$ mapping are beneficial in evaluating cartilage and meniscus. We aimed to evaluate the MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with IntUitive RElaxometry) sequences that provide morphologic images with clinical turbo spin-echo (TSE) contrasts and additional parameter maps versus reference TSE sequences in an in-situ model of human cartilage defects. MATERIALS AND METHODS: Prospectively, standardized cartilage defects of 8mm, 5mm, and 3mm diameter were created in the lateral femora of 10 human cadaveric knee specimens (81$\pm$10 years, nine male/one female). Using a clinical 3T MRI scanner and knee coil, MIXTURE sequences combining (i) proton-density weighted fat-saturated (PD-w FS) images and T2 maps and (ii) T1-weighted images and T1$\rho$ maps were acquired before and after defect creation, alongside the corresponding 2D TSE and 3D TSE reference sequences. Defect delineability, bone texture, and cartilage relaxation times were quantified. Inter-sequence comparisons were made using appropriate parametric and non-parametric tests. RESULTS: Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences. After defect creation, relaxation times increased significantly in the central femur (for T2) and all regions combined (for T1$\rho$). CONCLUSION: MIXTURE sequences permit time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1$\rho$ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defect delineability and bone texture, were comparable between MIXTURE and corresponding reference sequences.Comment: 12 pages (main body), 3 tables, 6 figure

Two for One -- Combined Morphologic and Quantitative Knee Joint MRI Using a Versatile Turbo Spin-Echo Platform

Introduction: Quantitative MRI techniques such as T2 and T1\r{ho} mapping are beneficial in evaluating knee joint pathologies; however, long acquisition times limit their clinical adoption. MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with IntUitive RElaxometry) provides a versatile turbo spin-echo (TSE) sequence platform for simultaneous morphologic and quantitative joint imaging yet lacks comparative evaluation in basic and translational research contexts. Methods: Two MIXTURE sequences were designed along clinical requirements: (i) MIX1, combining proton density (PD)-weighted fat-saturated (FS) images and quantitative T2 mapping (acquisition time: 4:59 min), and (ii) MIX2, combining T1-weighted images with quantitative T1\r{ho} mapping (6:38 min). MIXTURE sequences and their reference 2D and 3D TSE counterparts were acquired from ten human cadaveric knee joints using a clinical 3T MRI scanner and knee coil. Contrast, contrast-to-noise ratios, and coefficients of variation were comparatively evaluated using parametric tests. Clinical radiologists (n=3) assessed diagnostic quality as a function of sequence and anatomic structure using 5-point Likert scales and ordinal regression. The significance level was set to {\alpha}=0.01. Results: MIX1 and MIX2 had at least equal diagnostic quality compared to the 2D and 3D TSE sequences of the same image weighting. Contrast, contrast-to-noise ratios, and coefficients of variation were largely similar for the PD-weighted FS and T1-weighted images. Discussion: In clinically feasible scan times, the MIXTURE sequence platform yields (i) morphologic images of diagnostic quality and adjustable TSE-based contrasts and (ii) quantitative parameter mapping with additional insights on soft tissue composition and ultrastructure.Comment: 13 pages (main text), 7 figures, 3 table

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany

Abstract Background Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT). Methods Based on Bayes’ theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer’s perspective. Extensive sensitivity analyses were performed. Results Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (ΔQALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of €6,120 for one patient correctly diagnosed as having CAD and with €2,246 per ΔQALY gained versus €7,065 and €2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach. Conclusions In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR

Longitudinal T2 Mapping and Texture Feature Analysis in the Detection and Monitoring of Experimental Post-Traumatic Cartilage Degeneration

Background: Traumatic cartilage injuries predispose articulating joints to focal cartilage defects and, eventually, posttraumatic osteoarthritis. Current clinical-standard imaging modalities such as morphologic MRI fail to reliably detect cartilage trauma and to monitor associated posttraumatic degenerative changes with oftentimes severe prognostic implications. Quantitative MRI techniques such as T2 mapping are promising in detecting and monitoring such changes yet lack sufficient validation in controlled basic research contexts. Material and Methods: 35 macroscopically intact cartilage samples obtained from total joint replacements were exposed to standardized injurious impaction with low (0.49 J, n = 14) or high (0.98 J, n = 14) energy levels and imaged before and immediately, 24 h, and 72 h after impaction by T2 mapping. Contrast, homogeneity, energy, and variance were quantified as features of texture on each T2 map. Unimpacted controls (n = 7) and histologic assessment served as reference. Results: As a function of impaction energy and time, absolute T2 values, contrast, and variance were significantly increased, while homogeneity and energy were significantly decreased. Conclusion: T2 mapping and texture feature analysis are sensitive diagnostic means to detect and monitor traumatic impaction injuries of cartilage and associated posttraumatic degenerative changes and may be used to assess cartilage after trauma to identify “cartilage at risk”