Time-efficient combined morphologic and quantitative joint MRI: an in situ study of standardized knee cartilage defects in human cadaveric specimens.

BACKGROUND: Quantitative techniques such as T2 and T1ρ mapping allow evaluating the cartilage and meniscus. We evaluated multi-interleaved X-prepared turbo-spin echo with intuitive relaxometry (MIXTURE) sequences with turbo spin-echo (TSE) contrast and additional parameter maps versus reference TSE sequences in an in situ model of human cartilage defects. METHODS: Standardized cartilage defects of 8, 5, and 3 mm in diameter were created in the lateral femora of ten human cadaveric knee specimens (81 ± 10 years old; nine males, one female). MIXTURE sequences providing proton density-weighted fat-saturated images and T2 maps or T1-weighted images and T1ρ maps as well as the corresponding two- and three-dimensional TSE reference sequences were acquired before and after defect creation (3-T scanner; knee coil). Defect delineability, bone texture, and cartilage relaxation times were quantified. Appropriate parametric or non-parametric tests were used. RESULTS: Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences (p ≤ 0.47). After defect creation, relaxation times significantly increased in the central femur (T2pre = 51 ± 4 ms [mean ± standard deviation] versus T2post = 56 ± 4 ms; p = 0.002) and all regions combined (T1ρpre = 40 ± 4 ms versus T1ρpost = 43 ± 4 ms; p = 0.004). CONCLUSIONS: MIXTURE permitted time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1ρ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defects and bone texture, were comparable between MIXTURE and reference sequences. RELEVANCE STATEMENT: Equally time-efficient and versatile, the MIXTURE sequence platform combines morphologic imaging using familiar contrasts, excellent image correspondence versus corresponding reference sequences and quantitative mapping information, thereby increasing the diagnostic value beyond mere morphology. KEY POINTS: • Combined morphologic and quantitative MIXTURE sequences are based on three-dimensional TSE contrasts. • MIXTURE sequences were studied in an in situ human cartilage defect model. • Morphologic image features, i.e., defect delineabilty and bone texture, were investigated. • Morphologic image features were similar between MIXTURE and reference sequences. • MIXTURE allowed time-efficient simultaneous morphologic and quantitative knee joint assessment.

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

Quantitative MRI techniques such as T2 and T1ρ 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) platform for simultaneous morphologic and quantitative joint imaging. Two MIXTURE sequences were designed along clinical requirements: "MIX1", combining proton density (PD)-weighted fat-saturated (FS) images and T2 mapping (acquisition time: 4:59 min), and "MIX2", combining T1-weighted images and T1ρ mapping (6:38 min). MIXTURE sequences and their reference 2D and 3D TSE counterparts were acquired from ten human cadaveric knee joints at 3.0 T. 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 five-point Likert scales and ordinal regression, with a significance level of α = 0.01. MIX1 and MIX2 had at least equal diagnostic quality compared to reference 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. In clinically feasible scan times, MIXTURE sequences yield morphologic, TSE-based images of diagnostic quality and quantitative parameter maps with additional insights on soft tissue composition and ultrastructure.

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".

Automated Analysis of Alignment in Long-Leg Radiographs by Using a Fully Automated Support System Based on Artificial Intelligence.

PURPOSE: To develop and validate a deep learning-based method for automatic quantitative analysis of lower-extremity alignment. MATERIALS AND METHODS: In this retrospective study, bilateral long-leg radiographs (LLRs) from 255 patients that were obtained between January and September of 2018 were included. For training data (n = 109), a U-Net convolutional neural network was trained to segment the femur and tibia versus manual segmentation. For validation data (n = 40), model parameters were optimized. Following identification of anatomic landmarks, anatomic and mechanical axes were identified and used to quantify alignment through the hip-knee-ankle angle (HKAA) and femoral anatomic-mechanical angle (AMA). For testing data (n = 106), algorithm-based angle measurements were compared with reference measurements by two radiologists. Angles and time for 30 random radiographs were compared by using repeated-measures analysis of variance and one-way analysis of variance, whereas correlations were quantified by using Pearson r and intraclass correlation coefficients. RESULTS: Bilateral LLRs of 255 patients (mean age, 26 years ± 23 [standard deviation]; range, 0-88 years; 157 male patients) were included. Mean Sørensen-Dice coefficients for segmentation were 0.97 ± 0.09 for the femur and 0.96 ± 0.11 for the tibia. Mean HKAAs and AMAs as measured by the readers and the algorithm ranged from 0.05° to 0.11° (P = .5) and from 4.82° to 5.43° (P < .001). Interreader correlation coefficients ranged from 0.918 to 0.995 (r range, P < .001), and agreement was almost perfect (intraclass correlation coefficient range, 0.87-0.99). Automatic analysis was faster than the two radiologists' manual measurements (3 vs 36 vs 35 seconds, P < .001). CONCLUSION: Fully automated analysis of LLRs yielded accurate results across a wide range of clinical and pathologic indications and is fast enough to enhance and accelerate clinical workflows.Supplemental material is available for this article.© RSNA, 2020See also commentary by Andreisek in this issue.

No pressure, no diamonds? - Static vs. dynamic compressive in-situ loading to evaluate human articular cartilage functionality by functional MRI.

Biomechanical Magnetic Resonance Imaging (MRI) of articular cartilage, i.e. its imaging under loading, is a promising diagnostic tool to assess the tissue's functionality in health and disease. This study aimed to assess the response to static and dynamic loading of histologically intact cartilage samples by functional MRI and pressure-controlled in-situ loading. To this end, 47 cartilage samples were obtained from the medial femoral condyles of total knee arthroplasties (from 24 patients), prepared to standard thickness, and placed in a standard knee joint in a pressure-controlled whole knee-joint compressive loading device. Cartilage samples' responses to static (i.e. constant), dynamic (i.e. alternating), and no loading, i.e. free-swelling conditions, were assessed before (δ0), and after 30 min (δ1) and 60 min (δ2) of loading using serial T1ρ maps acquired on a 3.0T clinical MRI scanner (Achieva, Philips). Alongside texture features, relative changes in T1ρ (Δ1, Δ2) were determined for the upper and lower sample halves and the entire sample, analyzed using appropriate statistical tests, and referenced to histological (Mankin scoring) and biomechanical reference measures (tangent stiffness). Histological, biomechanical, and T1ρ sample characteristics at δ0 were relatively homogenous in all samples. In response to loading, relative increases in T1ρ were strong and significant after dynamic loading (Δ1 = 10.3 ± 17.0%, Δ2 = 21.6 ± 21.8%, p = 0.002), while relative increases in T1ρ after static loading and in controls were moderate and not significant. Generally, texture features did not demonstrate clear loading-related associations underlying the spatial relationships of T1ρ. When realizing the clinical translation, this in-situ study suggests that serial T1ρ mapping is best combined with dynamic loading to assess cartilage functionality in humans based on advanced MRI techniques.

Accuracy of Chest CT for Differentiating COVID-19 from COVID-19 Mimics.

PURPOSE: To determine the performance of radiologists with different levels of expertise regarding the differentiation of COVID-19 from other atypical pneumonias. Chest CT to identify patients suffering from COVID-19 has been reported to be limited by its low specificity for distinguishing COVID-19 from other atypical pneumonias ("COVID-19 mimics"). Meanwhile, the understanding of the morphologic patterns of COVID-19 has improved and they appear to be fairly specific. MATERIALS AND METHODS: Between 02/2020 and 04/2020, 60 patients with COVID-19 pneumonia underwent chest CT in our department. Cases were matched with a comparable control group of 60 patients of similar age, sex, and comorbidities, who underwent chest CT prior to 01/2020 for atypical pneumonia caused by other pathogens. Included were other viral, fungal, and bacterial pathogens. All 120 cases were blinded to patient history and were reviewed independently by two radiologists and two radiology residents. Readers rated the probability of COVID-19 pneumonia according to the COV-RADS classification system. Results were analyzed using Clopper-Pearson 95 % confidence intervals, Youden's Index for test quality criteria, and Fleiss' kappa statistics. RESULTS: Overall, readers were able to correctly identify the presence of COVID-19 pneumonia in 219/240 (sensitivity: 91 %; 95 %-CI; 86.9 %-94.5 %), and to correctly attribute CT findings to COVID-19 mimics in 159/240 ratings (specificity: 66.3 %; 59.9 %-72.2 %), yielding an overall diagnostic accuracy of 78.8 % (378/480; 74.8 %-82.3 %). Individual reader accuracy ranged from 74.2 % (89/120) to 84.2 % (101/120) and did not correlate significantly with reader expertise. Youden's Index was 0.57. Between-reader agreement was moderate (κ = 0.53). CONCLUSION: In this enriched cohort, radiologists were able to distinguish COVID-19 from "COVID-19 mimics" with moderate diagnostic accuracy. Accuracy did not correlate with reader expertise. KEY POINTS: · In a scenario of direct comparison (no negative findings), CT allows the differentiation of COVID-19 from other atypical pneumonias ("COVID mimics") with moderate accuracy.. · Reader expertise did not significantly influence these results.. · Despite similar patterns and distributions of pulmonary findings, radiologists were able to estimate the probability of COVID-19 pneumonia using the COV-RADS classification in a standardized manner in the larger proportion of cases.. CITATION FORMAT: · Sähn M, Yüksel C, Keil S et al. Accuracy of Chest CT for Differentiating COVID-19 from COVID-19 Mimics. Fortschr Röntgenstr 2021; 193: 1081 - 1091.

A serial multiparametric quantitative magnetic resonance imaging study to assess proteoglycan depletion of human articular cartilage and its effects on functionality.

Water, collagen, and proteoglycans determine articular cartilage functionality. If altered, susceptibility to premature degeneration is increased. This study investigated the effects of enzymatic proteoglycan depletion on cartilage functionality as assessed by advanced Magnetic Resonance Imaging (MRI) techniques under standardized loading. Lateral femoral condylar cartilage-bone samples from patients undergoing knee replacement (n = 29) were serially imaged by Proton Density-weighted and T1, T1ρ, T2, and T2* mapping sequences on a clinical 3.0 T MRI scanner (Achieva, Philips). Using pressure-controlled indentation loading, samples were imaged unloaded and quasi-statically loaded to 15.1 N and 28.6 N, and both before and after exposure to low-concentrated (LT, 0.1 mg/mL, n = 10) or high-concentrated trypsin (HT, 1.0 mg/mL, n = 10). Controls were not treated (n = 9). Responses to loading were assessed for the entire sample and regionally, i.e. sub- and peri-pistonally, and zonally, i.e. upper and lower sample halves. Trypsin effects were quantified as relative changes (Δ), analysed using appropriate statistical tests, and referenced histologically. Histological proteoglycan depletion was reflected by significant sub-pistonal decreases in T1 (p = 0.003) and T2 (p = 0.008) after HT exposure. Loading-induced changes in T1ρ and T2* were not related. In conclusion, proteoglycan depletion alters cartilage functionality and may be assessed using serial T1 and T2 mapping under loading.

Identifying the imaging correlates of cartilage functionality based on quantitative MRI mapping - The collagenase exposure model.

Cartilage functionality is determined by tissue structure and composition. If altered, cartilage is predisposed to premature degeneration. This pathomimetical study of early osteoarthritis evaluated the dose-dependant effects of collagenase-induced collagen disintegration and proteoglycan depletion on cartilage functionality as assessed by serial T1, T1ρ, T2, and T2* mapping under loading. 30 human femoral osteochondral samples underwent imaging on a clinical 3.0 T MRI scanner (Achieva, Philips) in the unloaded reference configuration (δ0) and under pressure-controlled quasi-static indentation loading to 15.1 N (δ1) and to 28.6 N (δ2). Imaging was performed before and after exposure to low (LC, 0.5 mg/mL; n = 10) or high concentration (HC, 1.5 mg/mL; n = 10) of collagenase. Untreated samples served as controls (n = 10). Loading responses were determined for the entire sample and the directly loaded (i.e. sub-pistonal) and bilaterally adjacent (i.e. peri­pistonal) regions, referenced histologically, quantified as relative changes, and analysed using adequate parametric and non-parametric statistical tests. Dose-dependant surface disintegration and tissue loss were reflected by distinctly different pre- and post-exposure response-to-loading patterns. While T1 generally decreased with loading, regardless of collagenase exposure, T1ρ increased significantly after HC exposure (p = 0.008). Loading-induced decreases in T2 were significant after LC exposure (p = 0.006), while changes in T2* were ambiguous. In conclusion, aberrant loading-induced changes in T2 and T1ρ reflect moderate and severe matrix changes, respectively, and indicate the close interrelatedness of matrix changes and functionality in cartilage.

Detection of Early-Stage Degeneration in Human Articular Cartilage by Multiparametric MR Imaging Mapping of Tissue Functionality.

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young's modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student's t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

Functional in situ assessment of human articular cartilage using MRI: a whole-knee joint loading device.

The response to loading of human articular cartilage as assessed by magnetic resonance imaging (MRI) remains to be defined in relation to histology and biomechanics. Therefore, an MRI-compatible whole-knee joint loading device for the functional in situ assessment of cartilage was developed and validated in this study. A formalin-fixed human knee was scanned by computed tomography in its native configuration and digitally processed to create femoral and tibial bone models. The bone models were covered by artificial femoral and tibial articular cartilage layers in their native configuration using cartilage-mimicking polyvinyl siloxane. A standardized defect of 8 mm diameter was created within the artificial cartilage layer at the central medial femoral condyle, into which native cartilage samples of similar dimensions were placed. After describing its design and specifications, the comprehensive validation of the device was performed using a hydraulic force gauge and digital electronic pressure-sensitive sensors. Displacement-controlled quasi-static uniaxial loading to 2.5 mm [Formula: see text] and 5.0 mm [Formula: see text] of the mobile tibia versus the immobile femur resulted in forces of [Formula: see text] N [Formula: see text] and [Formula: see text] N [Formula: see text] (on the entire joint) and local pressures of [Formula: see text] MPa [Formula: see text] and [Formula: see text] MPa [Formula: see text] (at the site of the cartilage sample). Upon confirming the MRI compatibility of the set-up, the response to loading of macroscopically intact human articular cartilage samples ([Formula: see text]) was assessed on a clinical 3.0-T MR imaging system using clinical standard proton-density turbo-spin echo sequences and T2-weighted multi-spin echo sequences. Serial imaging was performed at the unloaded state [Formula: see text] and at consecutive loading positions (i.e. at [Formula: see text] and [Formula: see text]. Biomechanical unconfined compression testing (Young's modulus) and histological assessment (Mankin score) served as the standards of reference. All samples were histologically intact (Mankin score, [Formula: see text]) and biomechanically reasonably homogeneous (Young's modulus, [Formula: see text] MPa). They could be visualized in their entirety by MRI and significant decreases in sample height [[Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text] (repeated-measures ANOVA)] as well as pronounced T2 signal decay indicative of tissue pressurization were found as a function of compressive loading. In conclusion, our compression device has been validated for the noninvasive response-to-loading assessment of human articular cartilage by MRI in a close-to-physiological experimental setting. Thus, in a basic research context cartilage may be functionally evaluated beyond mere static analysis and in reference to histology and biomechanics.