Magnetic resonance imaging of human knee joint functionality under variable compressive in-situ loading and axis alignment.

Magnetic resonance imaging (MRI) under mechanical loading, commonly referred to as stress MRI, allows the evaluation of functional properties of intra- and periarticular tissues non-invasively beyond static assessment. Quantitative MRI can identify physiological and pathological responses to loading as indication of, potentially treatable, early degeneration and load transmission failure. Therefore, we have developed and validated an MRI-compatible pressure-controlled axial loading device to compress human knee specimens under variable loading intensity and axis deviation. Ten structurally intact human knee specimens (mean age 83.2 years) were studied on a 3.0T scanner (Achieva, Philips). Proton density-weighted fat-saturated turbo spin-echo and high-resolution 3D water selective 3D gradient-echo MRI scans were acquired sequentially at 10° joint flexion in seven configurations: unloaded and then at approximately half and full body weight loading in neutral, 10° varus and 10° valgus alignment, respectively. Following manual segmentation in both femorotibial compartments, cartilage thickness (ThC) was determined as well as meniscus extrusion (ExM). These measures were compared to computed tomography scans, histological grading (Mankin and Pauli scores), and biomechanical properties (Instantaneous Young's Modulus). Compartmental, regional and subregional changes in ThC and ExM were reflective of loading intensity and joint alignment, with the greatest changes observed in the medial compartment during varus and in the lateral compartment during valgus loading. These were not significantly associated with the histological tissue status or biomechanical properties. In conclusion, this study explores the physiological in-situ response of knee cartilage and meniscus, based on stress MRI, and as a function of loading intensity, joint alignment, histological tissue status, and biomechanical properties, as another step towards clinical implementation.

Biomechanical effects of posterior pedicle screw-based instrumentation using titanium versus carbon fiber reinforced PEEK in an osteoporotic spine human cadaver model.

BACKGROUND: Aim of this biomechanical investigation was to compare the biomechanical effects of a carbon fiber reinforced PEEK and titanium pedicle screw/rod device in osteoporotic human cadaveric spine. METHODS: Ten human fresh-frozen cadaveric lumbar spines (L1-L5) have been used and were randomized into two groups according to the bone mineral density. A monosegmental posterior instrumentation (L3-L4) using titanium pedicle screws and rods was carried out in group A and using carbon fiber reinforced PEEK in group B. A cyclic loading test was performed at a frequency of 3 Hz, starting with a peak of 500 N for the first 2000 cycles, up to 950 N for 100,000 cycles under a general preload with 100 N. All specimens were evaluated with regard to a potential collapse of the implanted pedicle screws. A CT supported digital measurement of cavities around the pedicle at 3 defined measuring points was performed. Finally, the maximum zero-time failure load of all specimens was determined using a universal testing machine (80% Fmax). FINDINGS: Regarding maximum axial force (group A: 2835 N, group B: 3006 N, p = 0.595) and maximum compression (group A: 11.67 mm, group B: 15.15 mm, p = 0.174) no statistical difference could be shown between the two groups. However, significant smaller cavity formation around the pedicle screws could be observed in group B (p = 0.007), especially around the screw tip (p < 0.001). INTERPRETATION: Carbon fiber reinforced PEEK devices seem to be advantageous in terms of microscopic screw loosening compared to titanium devices.

An MRI-compatible varus-valgus loading device for whole-knee joint functionality assessment based on compartmental compression: a proof-of-concept study.

OBJECTIVE: Beyond static assessment, functional techniques are increasingly applied in magnetic resonance imaging (MRI) studies. Stress MRI techniques bring together MRI and mechanical loading to study knee joint and tissue functionality, yet prototypical axial compressive loading devices are bulky and complex to operate. This study aimed to design and validate an MRI-compatible pressure-controlled varus-valgus loading device that applies loading along the joint line. METHODS: Following the device's thorough validation, we demonstrated proof of concept by subjecting a structurally intact human cadaveric knee joint to serial imaging in unloaded and loaded configurations, i.e. to varus and valgus loading at 7.5 kPa (= 73.5 N), 15 kPa (= 147.1 N), and 22.5 kPa (= 220.6 N). Following clinical standard (PDw fs) and high-resolution 3D water-selective cartilage (WATSc) sequences, we performed manual segmentations and computations of morphometric cartilage measures. We used CT and radiography (to quantify joint space widths) and histology and biomechanics (to assess tissue quality) as references. RESULTS: We found (sub)regional decreases in cartilage volume, thickness, and mean joint space widths reflective of areal pressurization of the medial and lateral femorotibial compartments. DISCUSSION: Once substantiated by larger sample sizes, varus-valgus loading may provide a powerful alternative stress MRI technique.

Signal changes in T2-weighted MRI of liver metastases under bevacizumab-A practical imaging biomarker?

OBJECTIVE: The purpose of this study was to investigate signal changes in T2-weighted magnetic resonance imaging of liver metastases under treatment with and without bevacizumab-containing chemotherapy and to compare these signal changes to tumor contrast enhancement. MATERIALS AND METHODS: Retrospective analysis of 44 patients, aged 36-84 years, who underwent liver magnetic resonance imaging including T2-weighted and dynamic contrast enhancement sequences. Patients received bevacizumab-containing (n = 22) or conventional cytotoxic chemotherapy (n = 22). Magnetic resonance imaging was obtained at baseline and at three follow-ups (on average 3, 6 and 9 months after initial treatment). Three independent readers rated the T2 signal intensity and the relative contrast enhancement of the metastases on a 5-point scale. RESULTS: T2 signal intensity of metastases treated with bevacizumab showed a significant (p<0.001) decrease in T2 signal intensity after initial treatment and exhibit compared to conventionally treated metastases significantly (p<0.001 for each follow-up) hypointense (bevacizumab: 0.70 ± 0.83 before vs. -1.55 ± 0.61, -1.91 ± 0.62, and -1.97 ± 0.52; cytotoxic: 0.73 ± 0.79 before vs. -0.69 ± 0.81, -0.71 ± 0.68, and -0.75 ± 0.65 after 3, 6, and 9 months, respectively). T2 signal intensity was strongly correlated with tumor contrast enhancement (r = 0.71; p<0.001). Intra-observer agreement for T2-signal intensity was substantial (κ = 0.75). The agreement for tumoral contrast enhancement between the readers was considerably lower (κ = 0.39). CONCLUSION: Liver metastases exhibit considerably hypointense in T2-weighted imaging after treatment with bevacizumab, in contrast to conventionally treated liver metastases. Therefore, T2-weighted imaging seems to reflect the effect of bevacizumab.

Multiphase CT-based prediction of Child-Pugh classification: a machine learning approach.

BACKGROUND: To evaluate whether machine learning algorithms allow the prediction of Child-Pugh classification on clinical multiphase computed tomography (CT). METHODS: A total of 259 patients who underwent diagnostic abdominal CT (unenhanced, contrast-enhanced arterial, and venous phases) were included in this retrospective study. Child-Pugh scores were determined based on laboratory and clinical parameters. Linear regression (LR), Random Forest (RF), and convolutional neural network (CNN) algorithms were used to predict the Child-Pugh class. Their performances were compared to the prediction of experienced radiologists (ERs). Spearman correlation coefficients and accuracy were assessed for all predictive models. Additionally, a binary classification in low disease severity (Child-Pugh class A) and advanced disease severity (Child-Pugh class ≥ B) was performed. RESULTS: Eleven imaging features exhibited a significant correlation when adjusted for multiple comparisons with Child-Pugh class. Significant correlations between predicted and measured Child-Pugh classes were observed (ρLA = 0.35, ρRF = 0.32, ρCNN = 0.51, ρERs = 0.60; p < 0.001). Significantly better accuracies for the prediction of Child-Pugh classes versus no-information rate were found for CNN and ERs (p ≤ 0.034), not for LR and RF (p ≥ 0.384). For binary severity classification, the area under the curve at receiver operating characteristic analysis was significantly lower (p ≤ 0.042) for LR (0.71) and RF (0.69) than for CNN (0.80) and ERs (0.76), without significant differences between CNN and ERs (p = 0.144). CONCLUSIONS: The performance of a CNN in assessing Child-Pugh class based on multiphase abdominal CT images is comparable to that of ERs.

Functional MRI Mapping of Human Meniscus Functionality and its Relation to Degeneration.

Meniscus pathology may promote early osteoarthritis. This study assessed human meniscus functionality (i.e. its response to loading) ex vivo based on quantitative T1, T1ρ, and T2 mapping as a function of histological degeneration and loading. Forty-five meniscus samples of variable degeneration were harvested from the lateral meniscus body region of 45 patients during total knee arthroplasties. Samples underwent serial mapping on a 3.0-T MRI scanner (Achieva, Philips) using a force-controlled and torque-inducing compressive loading device. Samples were measured at three loading positions, i.e. unloaded, loaded to 2 bar (compression force 37 N) and 4 bar (69 N). Histology (Pauli classification) and biomechanics (Elastic Modulus) served as references. Based on histology, samples were trichotomized as grossly intact (n = 14), mildly degenerative (n = 16), and moderate-to-severely degenerative (n = 15) and analyzed using appropriate parametric and non-parametric tests. For T1, we found loading-induced decreases in all samples, irrespective of degeneration. For T1ρ, zonal increases in intact (apex) and decreases in degenerative samples (base) were found, while for T2, changes were ambiguous. In conclusion, force-controlled loading and serial MR imaging reveal response-to-loading patterns in meniscus. Zonal T1ρ response-to-loading patterns are most promising in differentiating degeneration, while T1 and T2 aren't clearly related to degeneration.and may provide an imaging-based indication of functional tissue properties.

A multi-purpose force-controlled loading device for cartilage and meniscus functionality assessment using advanced MRI techniques.

Response to loading of soft tissues as assessed by advanced magnetic resonance imaging (MRI) techniques is a promising approach to evaluate tissue functionality beyond (statically obtained) structural and compositional features. As cartilage and meniscus pathologies are closely intertwined in osteoarthritis (OA) and beyond, both tissues should ideally be studied to elucidate further the underlying mechanisms involved in load transmission and its failure leading to OA. Hence, we devised, constructed and validated a dedicated MRI-compatible pneumatic force-controlled loading device to study cartilage and meniscus functionality in a standardized and reproducible manner and in reference to alternative tissue evaluation methods. Mechanical reference measurements using digital force sensors confirmed the reproducible application of forces in the range of 0-76N. To demonstrate the device's utility in a basic research context, MRI measurements of human articular cartilage (obtained from the lateral femoral condyle, n = 5) and meniscus (obtained from lateral meniscus body, n = 5) were performed in the unloaded (δ0) and loaded configurations (δ1: [cartilage] 0.75 bar corresponding to 15.1 N, [meniscus] 2 bar corresponding to 37.1 N; δ2: [cartilage] 1.5 bar corresponding to 28.6 N, [meniscus] 4 bar corresponding to 69.1 N). Cartilage samples were directly indented, while meniscus samples were subject to torque-induced compression using a dedicated lever compression device. Morphological MR Imaging using Proton Density-weighted sequences and quantitative MR Imaging using T2 and T1ρ mapping were performed serially and at high resolution. For reference, samples underwent subsequent biomechanical and histological reference evaluation. In conclusion, the force-controlled loading device has been validated for the non-invasive response-to-loading assessment of human cartilage and meniscus samples by advanced MRI techniques. Hereby, both tissues may be functionally evaluated in combination, beyond mere static analysis and in reference to histological and biomechanical measures.

Influence of additional cement augmentation on endplate stability in circumferential stabilisation of osteoporotic spine fractures.

BACKGROUND: Anterior stabilisation of osteoporotic spine fractures is uncommon but necessary in the case of complex vertebral body comminution. The purpose of this study was to investigate the effect of additional cement-augmentation on the endplate stability. METHODS: Twelve human cadaveric lumbar spines were divided in two groups: (A) posterior cement-augmented pedicle screw/rod-based instrumentation of L3 to L5, posterior decompression of L4/5 and partial corpectomy of L4 and (B) same experimental setup with additional cement-augmentation of the adjacent endplates. A cyclic loading test was performed at a frequency of 3 Hz, starting with a peak of 500 N for the first 2.000 cycles, up to 950 N for 100.000 cycles under a general preload with 50 N. All specimens were evaluated with regard to a potential collapse of the adjacent endplates. Subsequently, the maximum zero-time failure load of all specimens was determined using a universal testing machine. FINDINGS: The median T-score of bone density was -4.32 (range -2.97 to -5.59), distributed equally in the two groups (average age 83 years). The specimen of the endplate-augmented group showed a significant higher failure load compared to non-endplate-augmented cadavers (group A: 2038 N, group B: 2990 N, p = 0.03). All specimens passed the full cyclic loading protocol with 100.000 cycles. No significant difference was observable regarding the adjacent endplate subsidence. INTERPRETATION: Additional cement augmentation in circumferential stabilisation resulted in a significant enhancement of the endplate stability regarding the maximum axial load, while the cyclic loading did not significantly enhance the fatigue endurance of the vertebral endplates over the 100,000 cycles tested.

Differentiation of human cartilage degeneration by functional MRI mapping-an ex vivo study.

OBJECTIVE: To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage. METHODS: Upon IRB approval and written informed consent, 59 macroscopically intact osteochondral samples were obtained from the central lateral femoral condyles of patients undergoing total knee replacement. Spatially resolved T1, T2, T2*, and T1ρ maps were generated prior to and during displacement-controlled quasi-static indentation loading to 405 µm (Δ1/2) and 810 µm (Δ1). Upon manual segmentation, absolute qMRI parameters and loading-induced relative changes (δ1/2, δ1) were determined for the entire cartilage sample and distinct zones and regions. Based on their histologically determined degeneration as quantified according to Mankin (Mankin sum scores [MSS], range 0-14), samples were dichotomised into intact (int; MSS 0-4, n = 35) and early degenerative (ed, MSS 5-8, n = 24). RESULTS: For T1ρ, consistent loading-induced increases were found for δ1/2 and δ1. Throughout the entire sample, increases in T1ρ were significantly higher in early degenerative than in intact samples (Δ1/2(ed) = 23.8 [q25 = 18.1, q75 = 29.0] %; Δ1/2(int) = 12.7 [q25 = 5.9, q75 = 19.5] %; p < 0.0005), according to Wilcoxon's signed-rank test). Zonal and regional analysis revealed these changes to be most pronounced in the sub-pistonal area. No significant degeneration-dependent loading-induced changes were found for T1, T2, or T2*. CONCLUSION: Aberrant load-bearing of early degenerative cartilage may be detected using T1ρ mapping as a function of loading. Hence, the diagnostic differentiation of intact versus early degenerative cartilage may allow the reliable identification of early and potentially reversible cartilage degeneration, thereby opening new opportunities for diagnosis and treatment of cartilage pathologies. KEY POINTS: • T1ρ mapping of the cartilage response to loading allows the reliable identification of early degenerative changes ex vivo. • Distinct response-to-loading patterns of cartilage tissue as assessed by functional MRI techniques are associated with biomechanical and histological tissue properties. • Non-invasive functional MR imaging techniques may facilitate the more sensitive monitoring of therapeutic outcomes and treatment strategies.

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.

T2 MR imaging vs. computational modeling of human articular cartilage tissue functionality.

The detection of early stages of cartilage degeneration remains diagnostically challenging. One promising non-invasive approach is to functionally assess the tissue response to loading by serial magnetic resonance (MR) imaging in terms of T2 mapping under simultaneous mechanical loading. As yet, however, it is not clear which cartilage component contributes to the tissue functionality as assessed by quantitative T2 mapping. To this end, quantitative T2 maps of histologically intact cartilage samples (n=8) were generated using a clinical 3.0-T MR imaging system. Using displacement-controlled quasi-static indentation loading, serial T2 mapping was performed at three defined strain levels and loading-induced relative changes were determined in distinct regions-of-interest. Samples underwent conventional biomechanical testing (by unconfined compression) as well as histological assessment (by Mankin scoring) for reference purposes. Moreover, an anisotropic hyperelastic constitutive model of cartilage was implemented into a finite element (FE) code for cross-referencing. In efforts to simulate the evolution of compositional and structural intra-tissue changes under quasi-static loading, the indentation-induced changes in quantitative T2 maps were referenced to underlying changes in cartilage composition and structure. These changes were parameterized as cartilage fluid, proteoglycan and collagen content as well as collagen orientation. On a pixel-wise basis, each individual component correlation with T2 relaxation times was determined by Spearman's ρs and significant correlations were found between T2 relaxation times and all four tissue parameters for all indentation strain levels. Thus, the biological changes in functional MR Imaging parameters such as T2 can further be characterized to strengthen the scientific basis of functional MRI techniques with regards to their perspective clinical applications.

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.

Anxiety of patients undergoing CT imaging-an underestimated problem?

RATIONALE AND OBJECTIVES: Prospective evaluation of anxiety in patients undergoing computed tomography (CT) imaging using a standardized state-trait anxiety inventory (STAI-S) and identification of possible risk factors. MATERIAL AND METHODS: During a 9-month interval, patients undergoing CT were questioned using STAI-S. Additionally, 10 questions concerning specific procedure-related features (claustrophobia, radiation, administration of contrast, and so forth) were added. Moreover, sex, age, admitting subspecialty, organ region, reason for imaging, and prior imaging studies were recorded. Statistical analysis was performed using the Student t test and linear regression analysis; significance level was set to 5%. RESULTS: Of 6122 patients, 825 patients undergoing CT (14%) were included (67% men; average age, 54 ± 17 years). Average STAI was 42 ± 10 with women (45 ± 11 vs. 41 ± 10; P < .001) and patients who received intravenous contrast (43 ± 10 vs. 42 ± 11; P = .021) showing significantly higher anxiety levels compared to those without contrast. Patients with investigations of their extremities (41 ± 11 vs. 43 ± 10; P = .020) and trauma patients (41 ± 11 vs. 43 ± 10; P = .006) revealed significantly lower STAI results. Patients who had never received a CT scan before showed significantly greater STAI-S values than those with repeat studies (42 ± 10 vs. 41 ± 11; P = .036). Females had greater fears concerning examination results (P < .001), radiation exposure (P = .032), administration of contrast (P = .014), and claustrophobia (P < .001). Patients with known malignancies had a significantly higher level of anxiety concerning their CT results (P = .002). CONCLUSIONS: Anxiety does not only occur before MRI but also occur before CT. Its sources are manifold and include communication of CT results, administration of contrast agents, radiation exposure, and claustrophobia. In this setting, women seemed to be more receptive than men.