T2 Relaxation Time Measurements Research Articles

Quantitative MRI assessment of joint effusion using T2-relaxometry at 3 Tesla: a feasibility and reproducibility study.

T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71ms; circular ROI: LoA = 146ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO:ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63ms; circular ROI: LoA = 41ms). T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility.

Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation.

T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. Prospective. 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. 3T, multiecho spin-echo sequence. T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2 -weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. 2 TECHNICAL EFFICACY: Stage 1.

Multi-echo single-shot spectroscopy combined with simultaneous 2D model fitting for fast and accurate measurement of metabolite-specific concentrations and T2 relaxation times.

The purpose of the current study was to develop a novel single-voxel MR spectroscopy acquisition scheme to simultaneously determine metabolite-specific concentrations and transverse relaxation times within realistic clinical scan times. Partly truncated multi-TE data are acquired as an echo train in a single acquisition (multi-echo single-shot [MESS]). A 2D multiparametric model fitting approach combines truncated, low-resolved short TE data with fully sampled, highly resolved, longer TE data to yield concentration and T2 estimates for major brain metabolites simultaneously. Cramer-Rao lower bounds (CRLB) are used as a measure of performance. The novel scheme was compared with traditional multi-echo multi-shot methods. In silico, in vitro, and in vivo experiments support the findings. MESS schemes, requiring only 2 min 12s for the acquisition of three echo times, provide valid concentration and relaxation estimates for multiple metabolites and outperform traditional methods for simultaneous determinations of metabolite-specific T2 s and concentrations, with improvements ranging from 5% to 30% for T2 s and from 10% to 50% for concentrations. However, substantial unsuppressed residual water signals may hamper the method's reproducibility, as observed in an initial experiment setup that prioritizes short TEs with severely truncated acquisition for the benefit of signal-to-noise ratio (SNR). Nevertheless, CRLB have been confirmed to be well suited as design criteria, and within-session repeatability approaches CRLB when residual water is removed in postprocessing by exploiting longer and less truncated data recordings. MESS MRS combined with 2D model fitting promises comparable accuracy, increased precision, or inversely shorter experimental times compared with traditional approaches. However, the optimal design must be investigated as a trade-off between SNR, the truncation factor, and TE batch selections, all of which influence the robustness of estimations.

3D T1 relaxation time measurements in an equine model of subtle post-traumatic osteoarthritis using MB-SWIFT.

The aim of this study is to assess whether articular cartilage changes in an equine model of post-traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very subtle sharp grooves, could be detected with ex vivo T1 relaxation time mapping utilizing three-dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T1 relaxation times of the samples (n = 8 + 8 for experimental and n = 12 for contralateral controls) were measured with a variable flip angle 3D multiband-sweep imaging with Fourier transform sequence. Equilibrium and instantaneous Young's moduli and proteoglycan (PG) content from OD of Safranin-O-stained histological sections were measured and utilized as reference parameters for the T1 relaxation times. T1 relaxation time was significantly (p < 0.05) increased in both groove areas, particularly in the blunt grooves, compared with control samples, with the largest changes observed in the superficial half of the cartilage. T1 relaxation times correlated weakly (Rs ≈ 0.33) with equilibrium modulus and PG content (Rs ≈ 0.21). T1 relaxation time in the superficial articular cartilage is sensitive to changes induced by the blunt grooves but not to the much subtler sharp grooves, at the 39-week timepoint post-injury. These findings support that T1 relaxation time has potential in detection of mild PTOA, albeit the most subtle changes could not be detected.

Comparing CT and MR Properties of Artificial Thrombi According to Their Composition.

This study aims to determine whether and to what extent the structure and composition of thrombi can be assessed using NMR and CT measurements. Seven different thrombus models, namely, six RBC thrombi with hematocrit levels (HTs) of 0%, 20%, 40%, 60%, 80% and 100% and one platelet thrombus model, were analyzed using proton NMR at 100 MHz and 400 MHz, with measurements of T1 and T2 NMR relaxation times and measurements of the apparent diffusion coefficient (ADC). In addition, the thrombus models were CT-scanned in a dual-energy mode (80 kV and 140 kV) and in a single-energy mode (80 kV) to measure their CT numbers. The results confirmed that RBC thrombi can be distinguished from platelet thrombi by using ADC and CT number measurements in all three settings, while they cannot be distinguished by using T1 and T2 measurements. All measured parameters allowed for the differentiation of RBC thrombi according to their HT values, but the best sensitivity to HT was obtained with ADC and single-energy CT measurements. The importance of this study also lies in the potential application of its results for the characterization of actual thrombi in vivo.

Creating Solid Solutions of Metallocenes: Migration of Nickelocene into the Ferrocene Crystal Lattice in the Absence of a Solvent

Ferrocene and nickelocene do not react with each other in solution; however, the large impact of the paramagnetic component on the ferrocene 1H NMR signal linewidth and relaxation times has been quantified. Co-crystallization of ferrocene and nickelocene at any ratio from a solvent can be explained with both pure substances crystallizing in the same space group P21/n. As a new phenomenon, when a ferrocene single crystal is exposed to polycrystalline nickelocene in the absence of a solvent, the nickelocene migrates into the ferrocene crystal lattice and a mixed crystal is formed that retains its macroscopic shape. This process has been proven visually by cutting the single crystal. Mixing polycrystalline ferrocene with polycrystalline nickelocene at different molar ratios with a mortar and pestle leads to crystalline solid solutions with the corresponding molar ratios of both components. This migration of one organometallic component into an existing crystal lattice of another at ambient temperature in the absence of a solvent has not been described previously. Paramagnetic 1H solid-state NMR spectroscopy of static and rotating samples of dry ferrocene/nickelocene mixtures at varying ratios is used to prove and quantify the mixing of both metallocenes at the molecular level. A single-crystal X-ray structure of a 50/50 mixed crystal corroborates the NMR results that nickelocene and ferrocene are randomly distributed in the lattice and that the space group P21/n is retained. All ferrocene molecules in the mixed crystal lattice show a broadening of their 1H wideline signals and residual magic-angle spinning (MAS) lines at ambient temperature. The broadening of the ferrocene signals correlates with the nickelocene content. 1H T1 relaxation time measurements for the signals of ferrocene in samples with different amounts of nickelocene corroborate the assumption that the signal broadening is due to paramagnetic dipole–dipole relaxation of ferrocene molecules in the vicinity of nickelocene. Spatially separated ferrocene and nickelocene powders in one rotor show the solid-state NMR characteristics of the individual polycrystalline metallocenes. The described formation of solid solutions of metallocenes in the absence of a solvent will open new pathways to homogeneously mixed nanoparticles with desired metal ratios and dual-atom catalysts.

Imaging Non-alcoholic Fatty Liver Disease Model Using H-1 and F-19 MRI.

We explore the use of intravenously delivered perfluorocarbon (PFC) nanoemulsion and 19F MRI for detecting inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD). Correlative studies of 1H-based liver proton density fat fraction (PDFF) and T1 measurements and histology are also evaluated. C57BL/6 mice were fed standard or high-fat diet (HFD) for 6weeks to induce NAFLD. 1H MRI measurements of PDFF and T1 relaxation time were performed at baseline to assess NAFLD onset prior to administration of a PFC nanoemulsion to enable 19F MRI of liver PFC uptake. 1H and 19F MRI biomarkers were acquired at 2, 21, and 42days post-PFC to assess changes. Histopathology of liver tissue was performed at experimental endpoint. Significant increases in liver volume, PDFF, and total PFC uptake were noted in HFD mice compared to Std diet mice. Liver fluorine density and T1 relaxation time were significantly reduced in HFD mice. We demonstrated longitudinal quantification of multiple MRI biomarkers of disease in NAFLD mice. The changes in liver PFC uptake in HFD mice were compared with healthy mice that suggests that 19F MRI may be a viable biomarker of liver pathology.

Accuracy, repeatability, and reproducibility of T1 and T2 relaxation times measurement by 3D magnetic resonance fingerprinting with different dictionary resolutions

ObjectivesTo assess the accuracy, repeatability, and reproducibility of T1 and T2 relaxation time measurements by three-dimensional magnetic resonance fingerprinting (3D MRF) using various dictionary resolutions.MethodsThe ISMRM/NIST phantom was scanned daily for 10 days in two 3 T MR scanners using a 3D MRF sequence reconstructed using four dictionaries with varying step sizes and one dictionary with wider ranges. Thirty-nine healthy volunteers were enrolled: 20 subjects underwent whole-brain MRF scans in both scanners and the rest in one scanner. ROI/VOI analyses were performed on phantom and brain MRF maps. Accuracy, repeatability, and reproducibility metrics were calculated.ResultsIn the phantom study, all dictionaries showed high T1 linearity to the reference values (R2 > 0.99), repeatability (CV < 3%), and reproducibility (CV < 3%) with lower linearity (R2 > 0.98), repeatability (CV < 6%), and reproducibility (CV ≤ 4%) for T2 measurement. The volunteer study demonstrated high T1 reproducibility of within-subject CV (wCV) < 4% by all dictionaries with the same ranges, both in the brain parenchyma and CSF. Yet, reproducibility was moderate for T2 measurement (wCV < 8%). In CSF measurement, dictionaries with a smaller range showed a seemingly better reproducibility (T1, wCV 3%; T2, wCV 8%) than the much wider range dictionary (T1, wCV 5%; T2, wCV 13%). Truncated CSF relaxometry values were evident in smaller range dictionaries.ConclusionsThe accuracy, repeatability, and reproducibility of 3D MRF across various dictionary resolutions were high for T1 and moderate for T2 measurements. A lower-resolution dictionary with a well-defined range may be adequate, thus significantly reducing the computational load.Key Points• A lower-resolution dictionary with a well-defined range may be sufficient for 3D MRF reconstruction.• CSF relaxation times might be underestimated due to truncation by the upper dictionary range.• Dictionary with a higher upper range might be advisable, especially for CSF evaluation and elderly subjects whose perivascular spaces are more prominent.

Liver T1 relaxation time of the 'normal liver' in healthy Asians: measurement with MOLLI and B1-corrected VFA methods at 3T.

Liver T1 is a potential magnetic resonance imaging biomarker for liver diseases. This study aimed to determine the T1 relaxation time of the normal liver (PDFF<5%) in healthy Asian volunteers using modified look-locker inversion recovery (MOLLI) and B1 inhomogeneity-corrected variable flip angle (B1-corrected VFA). 60 healthy Asian volunteers without focal or diffuse liver disease underwent a liver scan at 3T magnetic resonance. Proton density fat fraction (PDFF) and liver stiffness measurements were applied for the quantification of liver fat and fibrosis. T1 mapping was performed with MOLLI and B1-corrected VFA sequences. Bland-Altman, linear regression, Student t-test, and one-way analysis of variance were used for statistical analysis. The mean T1 relaxation times of the whole liver were 901 ± 34 ms by MOLLI, and 948 ± 29 ms by B1-corrected VFA in healthy volunteers. There was a strong correlation (r = 0.86, p < 0.0001) for liver T1 between two T1 mapping methods. There were significant differences between the right and left lobes in liver T1 relaxation times using both methods (p < 0.05). Gender and Asian ethnic disparities had no impact on liver T1 relaxation times. T1 relaxation times of the normal liver (PDFF<5%) in healthy volunteers were established by MOLLI and B1-corrected VFA T1 mapping methods at 3T. It may provide suitable and robust baseline values for the assessment of liver diseases. Gender and Asian ethnic disparities do not impact liver T1 relaxation time measurements.

T1 reduction rate with Gd-EOB-DTPA determines liver function on both 1.5\xa0T and 3\xa0T MRI

Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child–Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126–0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.

Polymer/silica core–shell nanoparticles with temperature-dependent stability properties

This work aimed at the synthesis of hydrogel-based composite core/shell nanoparticles and their subsequent surface modification with thermoresponsive copolymers. Submicron hydrogel-based nanoparticles were obtained from the layer-by-layer coating of silica nanoparticles with two natural oppositely-charged polyelectrolytes, chitosan and sodium alginate. Further modifications with a PVAm-b-PNIPAM copolymer synthetized by RAFT polymerization was achieved by the “grafting to” approach. First, the optimum feed weight ratio (fwr) was determined by a combined approach of zeta potential and T2 relaxation time measurements. Then, diblock grafting at this optimum fwr was performed and characterized by XPS. XPS analysis confirmed the presence of copolymer at the particles’ surface with the increase of C and N atomic percentage. The quantification study was carried out by spectrofluorimetry using the fluorescently labeled PVAm-b-P(NIPAM-stat-NVC) copolymer and revealed that the grafting efficiency could reach 60 %. Finally, a study of thermosensivity properties confirmed that our smart system allowed a temperature-induced destabilization of the particles suspension at 45 °C. This work has promising prospects in the field of controlled drug delivery.

Relaxation time of brain tissue in the elderly assessed by synthetic MRI.

BackgroundSynthetic MRI (SyMRI) is a quantitative technique that allows measurements of T1 and T2 relaxation times (RTs). Brain RT evolution across lifespan is well described for the younger population. The aim was to study RTs of brain parenchyma in a healthy geriatric population in order to define the normal value of structures in this group population. Normal values for geriatric population could help find biomarker for age‐related brain disease.Materials and methodsFifty‐four normal‐functioning individuals (22 females, 32 males) with mean age of 83 years (range 56–98) underwent SyMRI. RT values in manually defined ROIs (centrum semiovale, middle cerebellar peduncles, thalamus, and insular cortex) and in segmented whole‐brain components (brain parenchyma, gray matter, white matter, myelin, CSF, and stromal structures) were extracted from the SyMRI segmentation software. Patients' results were combined into the group age. Main ROI‐based and whole‐brain results were compared for the all dataset and for age group results as well.ResultsFor white matter, RTs between ROI‐based analyses and whole‐brain results for T2 and for T1 were statistically different and a trend of increasing T1 in centrum semiovale and cerebellar peduncle was observed. For gray matter, thalamic T1 was statistically different from insular T1. A difference was also found between left and right insula (p < .0001). T1 RTs of ROI‐based and whole‐brain‐based analyses were statistically different (p < .0001). No significant difference in T1 and T2 was found between age groups on ROI‐based analysis, but T1 in centrum semiovale and thalamus increased with age. No statistical difference between age groups was found for the various segmented volumes except for myelin between 65–74 years of age and the 95–105 years of age groups (p = .038).ConclusionsSyMRI is a new tool that allows faster imaging and permits to obtain quantitative T1 and T2. By defining RT values of different brain components of normal‐functioning elderly individuals, this technique may be used as a biomarker for clinical disorders like dementia.

Volume and T2 relaxation time measurements of quadriceps femoris and hamstring muscles are reliable and reproducible

Background/aimVolume and T2 relaxation time measurements of the skeletal muscle provide quantitative information. We aimed to evaluate the interobserver reliability and the intraobserver reproducibility of measurements of volumes and T2 relaxation times of the quadriceps femoris and the hamstring muscles.Materials and methodsA cross-sectional reliability study was conducted on ten recreational athletes. The images of the quadriceps and the hamstring muscles of both limbs were obtained using a 3.0 Tesla magnetic resonance imaging (MRI) scanner. Two sports medicine specialists measured muscle volumes from a total of 2560 images and T2 relaxation times from a total of 40 images, and repeated this once more. The intraobserver and interobserver compliance were assessed by the intraclass correlation coefficient (ICC) and Cronbach’s alpha (α).ResultsVolume and T2 relaxation time of quadriceps femoris and hamstring muscle measurements with MRI had good to excellent reliability (Muscle volume; intraobserver ICCs: between 0.97 and 0.99, α: between 0.98 and 0.99 and interobserver ICCs: between 0.96 and 0.99, α: 0.99. T2 relaxation time; intraobserver ICCs: between 0.74 and 0.96, α: between 0.85 and 0.98 and interobserver ICCs: between 0.75 and 0.90, α: between 0.85 and 0.95).ConclusionVolume and T2 relaxation time measurements of the quadriceps femoris and the hamstring muscles are reliable and reproducible.

3Tesla post-mortem MRI quantification of anatomical brain structures

Quantitative post-mortem magnetic resonance imaging (PMMR) allows for measurement of T1 and T2 relaxation times and proton density (PD) of brain tissue. Quantitative PMMR values may be used for advanced post-mortem neuro-imaging diagnostics such as computer aided diagnosis. So far, the quantitative T1, T2 and PD post-mortem values of regular anatomical brain structures were unknown for a 3 Tesla PMMR application. The goal of this basic research study was to evaluate the quantitative values of post-mortem brain structures for a 3 T post-mortem magnetic resonance application with regard to various corpse temperatures. In 50 forensic cases, a quantitative PMMR brain sequence was applied prior to autopsy. Measurements of T1 (in ms), T2 (in ms), and PD (in %) values of cerebrum (Group 1: frontal grey matter, frontal white matter, thalamus, caudate nucleus, globus pallidus, putamen, internal capsule) brainstem and cerebellum (Group 2: cerebral peduncle, substantia nigra, red nucleus, pons, middle cerebellar peduncle, cerebellar hemisphere, medulla oblongata) were conducted in synthetically calculated axial PMMR brain images. Assessed quantitative values were corrected for corpse temperature. Temperature dependence was observed mainly for T1 values. ANOVA testing resulted in significant differences of quantitative values between the investigated anatomical brain structures in both groups. It can be concluded that temperature corrected 3 Tesla PMMR T1, T2 and PD values are feasible for characterization and discrimination of regular anatomical brain structures. This may provide a base for future advanced diagnostics of forensically relevant brain lesions and pathology.

Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence

BackgroundAxonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI).ObjectiveBy using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children.Materials and methodsAverage R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE.ResultsR1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74–0.76±0.04 s−1) and lowest for the corpus callosum (0.37–0.44±0.03 s−1). The myelination rate is fastest in the corpus callosum and slowest in the deep grey matter. R1 is decreased in hypo- and dysmyelination disorders. Myelin maturation is clearly visible on MP2RAGE, especially in the first year of life.ConclusionMP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures.

Cardiac MRI findings in patients with Crohn's disease.

Early cardiac death is more common in patients with Crohn's disease (CD) than in healthy adults, but the exact cause is unknown. The aim of this study is to investigate the cardiac magnetic resonance imaging (MRI) findings in patients with CD and compare the MRI findings with healthy controls (HCs). This study also aimed to demonstrate the possible cardiac involvement in patients with CD using MRI. In this prospective study, participants with CD (n = 20) and HC (n = 20) underwent cardiac MRI. Erythrocyte sedimentation rate (ESR) and hematocrit levels were investigated before MRI in both groups. Two observers evaluated the ventricular functional and morphological parameters in consensus. Myocardial T1/T2-relaxation times were calculated by two observers independently using two different software, and hematocrit-corrected left ventricle extracellular volume (LV-ECV) was calculated. Observer-2 also performed histogram analysis for T1/T2-mapping images. Patients with CD had a significantly higher LV-ECV, mildly decreased right ventricle ejection fraction, and prolonged T2-relaxation time than HC. Moreover, histogram analysis showed that the maximum and mean T2-relaxation times were higher in patients with CD. There was an excellent agreement between observers for the assessment of mean native and post-contrast T1-relaxation time (intraclass correlation coefficient (ICC) of 0.991 and ICC of 0.941, respectively) and mean T2-relaxation time measurements (ICC of 0.983). Moreover, mean T2-relaxation time was found to be significantly correlated with ESR. This study suggests visually undetectable myocardial involvement due to chronic systemic inflammation in patients with Crohn's disease. Cardiac MRI can help assess and monitor cardiac involvement in patients with CD.

Patellar instability MRI measurements are associated with knee joint degeneration after reconstruction of the medial patellofemoral ligament

ObjectiveTo qualitatively and quantitatively evaluate the 2-year magnetic resonance imaging (MRI) outcome after MPFL reconstruction at the knee and to assess MRI-based risk factors that predispose for inferior clinical and imaging outcomes.Materials and methodsA total of 31 patients with MPFL reconstruction were included (22 ± 6 years, 10 female). MRI was performed preoperatively in 21/31 patients. Two-year follow-up MRI included quantitative cartilage T2 and T1rho relaxation time measurements at the ipsilateral and contralateral knee. T2relative was calculated as T2patellofemoral/T2femorotibial. Morphological evaluation was conducted via WORMS scores. Patellar instability parameters and clinical scores were obtained. Statistical analyses included descriptive statistics, t-tests, multivariate regression models, and correlation analyses.ResultsTwo years after MPFL reconstruction, all patellae were clinically stable. Mean total WORMS scores improved significantly from baseline to follow-up (mean difference ± SEM, − 4.0 ± 1.3; P = 0.005). As compared to patients with no worsening of WORMS subscores over time (n = 5), patients with worsening of any WORMS subscore (n = 16) had lower trochlear depth, lower facetal ratio, higher tibial-tuberosity to trochlear groove (TTTG) distance, and higher postoperative lateral patellar tilt (P < 0.05). T2relative was higher at the ipsilateral knee (P = 0.010). T2relative was associated with preoperatively higher patellar tilt (P = 0.021) and higher TTTG distance (P = 0.034). TTTG distance, global T2 values, and WORMS progression correlated with clinical outcomes (P < 0.05).ConclusionMPFL reconstruction is an optimal treatment strategy to restore patellar stability. Still, progressive knee joint degeneration and patellofemoral cartilage matrix degeneration may be observed, with patellar instability MRI parameters representing particular risk factors.

Reproducibility of T1 relaxation times in diagnostic MRI: A phantom study

T1 mapping is crucial for many quantitative magnetic resonance imaging (MRI) procedures. However, studies have reported wide T1 variations, both in vivo and in vitro. Since clinical decisions depend on T1 relaxation times, evaluating the factors affecting their reproducibility is necessary. Available studies are limited in that they do not provide a comparative perspective on the variation of T1 relaxation times as a function of relevant parameters, such as pulse sequence type, magnetic field strength and how their interplay with the scanner model affects the resulting T1 values. To address these gaps, we imaged two phantoms modelling T1 of different samples at 1.5 T and 3.0 T using fast and slow inversion recovery (IR) sequences. The results show that T1 relaxation times from 3.0 T scanners are accurate and reproducible in terms of the expected reference values and when compared between different scanner models. Similarly, T1 values measured with the two pulse sequences were similar for all 3.0 T scanners. On the contrary, 1.5 T scanners exhibited larger discrepancies in the measured T1 compared with the reference values. In addition, 1.5 T scanners displayed less reproducibility in T1 relaxation time measurements across different 1.5 T scanners, and pulse sequences.

POS0277 ANABOLIC EFFECT OF LNA043, A NOVEL DISEASE-MODIFYING OSTEOARTHRITIS DRUG CANDIDATE: RESULTS FROM AN IMAGING-BASED PROOF-OF-CONCEPT TRIAL IN PATIENTS WITH FOCAL ARTICULAR CARTILAGE LESIONS

Background:LNA043 is a modified, recombinant version of the human angiopoietin-like 3 (ANGPTL3) protein acting directly on cartilage-resident cells to transmit its cartilage anabolic effect. A first-in-human study previously demonstrated the favourable safety profile and the modulation of several pathways involved in cartilage homeostasis and osteoarthritis (OA)1. A previous proof-of-mechanism imaging study used high field (7 Tesla) magnetic resonance imaging (MRI) to show formation of hyaline-like tissue after a single injection of 20 mg LNA043 (unpublished data).Objectives:To evaluate non-invasively the chondro-regenerative capacity of multiple intra-articular (i.a.) injections of LNA043 in patients with articular cartilage lesions in the knee (NCT03275064).Methods:This was a randomised, double-blind, placebo (PBO)-controlled, proof-of-concept study in patients with a partial thickness cartilage lesion. In total, 58 patients (43 [20 mg LNA043]; 15 [PBO]), stratified by lesion type (condylar or patellar) were treated with 4 weekly i.a. injections. The primary endpoint was T2 relaxation time measurement as a marker of collagen fiber network, and cartilage lesion-volume was a secondary endpoint, both using 3-Tesla MRI. Assessments were performed at baseline, weeks (wks) 8, 16, 28 and 52 (the latter in 23/58 patients). While lesion-volume for the secondary endpoint was determined from manually segmented images, the cartilage volume of 21 sub-regions spanning the entire knee was also measured from 3D isotropic MR images employing an automated segmentation prototype software (MR Chondral Health 2.1 [MRCH], Siemens Healthcare)2. An exploratory analysis evaluated the treatment effect for the additive volume of the 3 subregions in the weight-bearing area of the medial femur.Results:No change in T2 relaxation time was detected between treatment and PBO groups. Manual segmentation showed continuous filling of the cartilage lesions up to wk 28 in LNA043-treated patients with femoral lesions (p=0.08, vs PBO) while no effect was detected for patients with patellar lesions. Given the limitations of measuring small, irregularly shaped lesions with manual image-analysis, the MRCH approach was used (Figure 1). In the medial femoral weight-bearing region, refilling was detected over time (Δ=123 mm3 at wk 28, N= 37, p= 0.05). No overgrowth was detected in the lateral femoral condyles without cartilage damage. The overall safety profile was favourable; only mild/moderate local reactions were reported, including a higher incidence of joint swelling (9.3% vs 0%) and arthralgia (11.6% vs 6.7%) for LNA043 vs PBO resolving spontaneously or with paracetamol/NSAIDs. No anti-drug antibodies were detected.Conclusion:Treatment with 4 weekly i.a. injections of 20 mg LNA043 resulted in regeneration of damaged cartilage in patients with femoral articular cartilage lesions. Automated measurement of cartilage volume in the femoral index region was able to detect a relevant treatment effect and was found to be more sensitive than the manual segmentation method. No sign of cartilage overgrowth was observed in healthy femoral regions. A Phase 2b study in patients with mild to moderate knee OA is in preparation.

MRI diffusion phantoms: ADC and relaxometric measurement comparisons between polyacrylamide and agarose gels

PurposeThe aim of this study is to compare polyacrylamide and agarose gels, as components of a simple MRI phantom, for the measurements of Apparent Diffusion Coefficient (ADC), T1 and T2 relaxation times. Materials and methodsFive (5) test tubes with polyacrylamide gels of different monomer concentrations and six (6) test tubes of different agarose gel concentrations were used as a phantom for ADC, T1 and T2 measurements, which were expressed as 2D color parametric maps, on a 1.5 T clinical MRI system. ADC and T2 maps were calculated utilizing a Weighted Linear (WL) regression fitting algorithm. T1 maps were calculated utilizing a standard non-linear fitting algorithm. ResultsIn agarose gels, ADC measurements are independent of the agarose concentration, whereas the T1 and T2 relaxation times decrease with increasing agarose concentration. On the contrary, in polyacrylamide gels, ADC measurements decrease quadratically while increasing the monomer concentration, whereas the T1 and T2 relaxation times reveal a linear decrease with increasing monomer concentration. ConclusionPolyacrylamide gels can serve as a better means for simulating ADC values, as compared with the agarose gels used in this study.