T2 Relaxation Time Measurements Research Articles

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.

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Physicochemical properties of wet-glycated soy proteins

On a lab-scale, glycation is generally a lengthy process that would be costly if replicated on an industrial scale. In this study, a simplified method for glycating soy protein isolate has been developed. Soy proteins were glycated with allulose, fructose, and glucose in the presence of water. Free amino group content, protein solubility, browning index, and reducing sugar concentration were measured for the glycated proteins. Fourier Transform Infrared (FT-IR) spectroscopy was used to examine structural changes, and hydration behavior was evaluated using Time Domain Nuclear Magnetic Resonance (TD-NMR) relaxometry through T2 relaxation time measurements. The results showed that proteins could be glycated under these austere conditions and with minimal control. It was found that high temperatures were not favorable for glycation, and lower temperatures could be preferred. At high temperatures, proteins become more denatured and less soluble, as shown through the Lowry method for protein solubility and TD-NMR results. Higher browning was observed at a higher temperature, primarily when allulose and fructose were used for glycation. The highest glycation was obtained with glucose, while allulose and fructose showed the lowest reactivity under the proposed conditions. Proteins with low solubility had longer T2 relaxation times, indicating more free water and weaker water-binding capability.

Quantitative 3-T Magnetic Resonance Imaging After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting of the Knee: The Importance of Subchondral Bone Parameters

Background: Matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) is an effective surgical treatment for osteochondral defects. Quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as noninvasive biomarkers to assess the biochemical composition of cartilage repair tissue. Purpose: To evaluate the association of quantitative MRI parameters of cartilage repair tissue and subchondral bone marrow with magnetic resonance morphologic and clinical outcomes after MACI with ABG of the knee. Study Design: Case series; Level of evidence, 4. Methods: Qualitative and quantitative 3 T MRI of the knee was performed in 21 patients (16 male) at 2.5 years after MACI with ABG at the medial (18/21) or lateral (3/21) femoral condyle for the treatment of osteochondral defects. Morphologic MRI sequences were assessed using MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. T2 relaxation time measurements for the assessment of cartilage repair tissue (CRT2) were obtained. Single-voxel magnetic resonance spectroscopy was performed in underlying subchondral bone marrow (BM) and at both central femoral condyles. The presence of pain and Tegner scores were noted. Statistical analyses included Student t tests, correlation analyses, and multivariate regression models. Results: The mean defect size was 4.9 ± 1.9 cm2. At a follow-up of 2.5 ± 0.3 years, 9 of 21 patients were asymptomatic. Perfect defect filling was achieved in 66.7% (14/21) of patients. MOCART 2.0 scores (74.1 ± 18.4) did not indicate pain (68.3 ± 19.0 [pain] vs 81.7 ± 15.4 [no pain]; P = .102). However, knee pain was present in 85.7% (6/7) of patients with deep bony defects (odds ratio, 8.0; P = .078). Relative CRT2 was higher in hypertrophic cartilage repair tissue than in repair tissue with normal filling (1.54 ± 0.42 vs 1.13 ± 0.21, respectively; P = .022). The underlying BM edema–like lesion (BMEL) volume was larger in patients with underfilling compared with patients with perfect defect filling (1.87 ± 1.32 vs 0.31 ± 0.51 cm3, respectively; P = .002). Patients with severe pain showed a higher BMEL volume (1.2 ± 1.3 vs 0.2 ± 0.4 cm3, respectively; P = .046) and had a higher BM water fraction (26.0% ± 12.3% vs 8.6% ± 8.1%, respectively; P = .026) than did patients without pain. Conclusion: Qualitative and quantitative MRI parameters including the presence of subchondral defects, CRT2, BMEL volume, and BM water fraction were correlated with cartilage repair tissue quality and clinical symptoms. Therefore, the integrity of subchondral bone was associated with outcomes after osteochondral transplantation.

Feasibility of T2 relaxation time in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids

Purpose The aim of this study was to assess the feasibility of T2 relaxation time in predicting the immediate technical outcome i.e., nonperfused volume ratio (NPVr) of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it with existing T2-weighted imaging methods (Funaki classification and scaled signal intensity, SSI). Materials and methods 30 patients with 32 uterine fibroids underwent an MRI study including a quantitative T2 relaxation time measurement prior to MRgHIFU treatment. T2 relaxation times were measured with a multi-echo fast imaging-based technique with 16 echoes. The correlation between pretreatment values of the uterine fibroids and treatment outcomes, that is nonperfused volume ratios (NPVr), was assessed with nonparametric statistical measures. T2 relaxation time-based method was compared to existing T2-weighted imaging-based methods using receiver-operating-characteristics (ROC) curve analysis and Chi-square test. Results Nonparametric measures of association revealed a statistically significant negative correlation between T2 relaxation time values and NPVr. The T2 relaxation time classification (T2 I, T2 II, and T2 III) resulted in the whole model p-value of 0.0019, whereas the Funaki classification resulted in a p-value of 0.56. The T2 relaxation time classification (T2 I and T2 II) achieved a whole model of a p-value of 0.0024, whereas the SSI classification had a p-value of 0.0749. Conclusions A longer T2 relaxation time of the fibroid prior to treatment correlated with a lower NPVr. Based on our results, the T2 relaxation time classifications seem to outperform the Funaki classification and the SSI method.

Cartilage T2 Relaxation Times and Subchondral Trabecular Bone Parameters Predict Morphological Outcome After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting

Background: Quantitative magnetic resonance (MR) imaging techniques are established for evaluation of cartilage composition and trabecular bone microstructure at the knee. It remains unclear whether quantitative MR parameters predict the midterm morphological outcome after matrix-associated chondrocyte implantation (MACI) with autologous bone grafting (ABG). Purpose: To assess longitudinal changes and associations of the biochemical composition of cartilage repair tissue, the subchondral bone architecture, and morphological knee joint abnormalities on 3-T MR imaging after MACI with ABG at the knee. Study Design: Case series; Level of evidence, 4. Methods: Knees of 18 patients (28.7 ± 8.4 years [mean ± SD]; 5 women) were examined preoperatively and 3, 6, 12, and 24 months after MACI and ABG using 3-T MR imaging. Cartilage composition was assessed using T2 relaxation time measurements. Subchondral bone microstructure was quantified using a 3-dimensional phase-cycled balanced steady-state free precision sequence. Trabecular bone parameters were calculated using a dual threshold algorithm (apparent bone fraction, apparent trabecular number, and apparent trabecular separation). Morphological abnormalities were assessed using the MOCART (magnetic resonace observation of cartilage repair tissue) score, the WORMS (Whole-Organ Magnetic Resonance Imaging Score), and the CROAKS (Cartilage Repair Osteoarthritis Knee Score). Clinical symptoms were assessed using the Tegner activity and Lysholm knee scores. Statistical analyses were performed by using multiple linear regression analysis. Results: Total WORMS (P = .02) and MOCART (P = .001) scores significantly improved over 24 months after MACI. Clinical symptoms were significantly associated with the presence of bone marrow edema pattern abnormalities 24 months after surgery (P = .035). Overall there was a good to excellent radiological outcome found after 24 months (MOCART score, 88.8 ± 10.1). Cartilage repair T2 values significantly decreased between 12 and 24 months after MACI (P = .009). Lower global T2 values after 3 months were significantly associated with better MOCART scores after 24 months (P = .04). Moreover, trabecular bone parameters after 3 months were significantly associated with the total WORMS after 24 months (apparent bone fraction, P = .048; apparent trabecular number, P = .013; apparent trabecular separation, P = .013). Conclusion: After MACI with ABG, early postoperative quantitative assessment of biochemical composition of cartilage and microstructure of subchondral bone may predict the outcome after 24 months. The perioperative global joint cartilage matrix quality is essential for proper proliferation of the repair tissue, reflected by MOCART scores. The subchondral bone quality of the ABG site is essential for proper maturation of the cartilage repair tissue, reflected by cartilage T2 values.

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents

The relaxivity of MRI contrast agents can be increased by increasing the size of the contrast agent and by increasing concentration of the bound gadolinium. Large multi-site ligands able to coordinate several metal centres show increased relaxivity as a result. In this paper, an “aza-type Michael” reaction is used to prepare cyclen derivatives that can be attached to organosilicon frameworks via hydrosilylation reactions. A range of organosilicon frameworks were tested including silsesquioxane cages and dimethylsilylbenzene derivatives. Michael donors with strong electron withdrawing groups could be used to alkylate cyclen on three amine centres in a single step. Hydrosilylation successfully attached these to mono-, di-, and tri-dimethylsilyl-substituted benzene derivatives. The europium and gadolinium complexes were formed and studied using luminescence spectroscopy and relaxometry. This showed the complexes to contain two bound water moles per lanthanide centre and T1 relaxation time measurements demonstrated an increase in relaxivity had been achieved, in particular for the trisubstituted scaffold 1,3,5-tris((pentane-sDO3A)dimethylsilyl)benzene-Gd3. This showed a marked increase in the relaxivity (13.1 r1p/mM−1s−1).

Quantitative magnetic resonance imaging: differentiating soft tissue implants and fillers used in cosmetic and reconstructive surgery.

To evaluate the value of synthetic magnetic resonance imaging (MRI) and T2 mapping in distinguishing between different types of fillers in soft tissues. Ex vivo fillers of buttock soft tissues (silicone, collagen, and different types of hyaluronic acid) were scanned using a synthetic MRI sequence at 1.5 and 3T and an optimized T2 mapping sequence to measure the T2 relaxation times of the fillers ex vivo. Three patients addressed to assess complications with buttock fillers underwent MRI with the standard morphological sequences and an additional synthetic MRI sequence; T2 mapping was not performed for the patients. Two patients had silicone fillers, whereas the exact filler composition for the third patient was unknown. Measurements of T1 and T2 relaxation times of ex vivo fillers at 1.5 and 3T using synthetic MRI showed that the silicone, collagen, and hyaluronic acid had distinct relaxation time characteristics. In vivo, the synthetic MRI correctly identified silicone in the two patients with known silicone fillers, showing low T1 and T2 values, whereas in the third patient with an unknown filler type, the synthetic MRI suggested a collagen filler, with intermediate relaxation time values. Quantitative sequences have the potential to differentiate between filler types in a noninvasive fashion.

Myocardial T1 mapping using SMART1 Map and MOLLI mapping in asymptomatic patients with recent extracardiac sarcoidosis.

Sarcoidosis is a systemic granulomatous disease affecting in particular the respiratory tract. Cardiac magnetic resonance (CMR), including a measurement of T1 relaxation time, could potentially detect early stadia of sarcoidosis of the heart. The study aims to assess T1 mapping in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. One hundred and twenty patients with extracardiac sarcoidosis and without any heart disease history were included. One hundred and thirteen of them underwent a CMR examination. The mean time from the diagnosis of sarcoidosis was 0.8 (0.2-3.3) years. Cine images for the assessment of left ventricular (LV) functional parameters and pre- and post-contrast saturation method using adaptive recovery times for cardiac T1 mapping (SMART1 Map) and modified Look-Locker inversion recovery (MOLLI) images were acquired for the assessment of native T1 relaxation time and extracellular volume (ECV). The measured parameters were compared between sarcoidosis patients and 22 controls. The sarcoidosis patients had normal global and regional systolic LV function-LV ejection fraction 65 ± 5% versus 66 ± 7% (p NS). The mean native T1 relaxation times were not prolonged-1465 ± 93 ms versus 1480 ± 88 ms (p NS) measured by SMART1 Map and 1317 ± 60 ms versus 1313 ± 83 ms (p NS) measured using a MOLLI sequence. Similarly, the mean ECV values did not increase-16.9 ± 3.9% versus 17.9 ± 3.7% (p NS) measured by SMART1 Map and 30.9 ± 2.9% versus 31.6 ± 8.3% (p NS) measured using a MOLLI sequence. Myocardial native T1 relaxation times were not prolonged and ECV was not increased in asymptomatic patients with extracardiac sarcoidosis.

Accelerated T2 Mapping of the Lumbar Intervertebral Disc: Highly Undersampled K-Space Data for Robust T2 Relaxation Time Measurement in Clinically Feasible Acquisition Times.

Fifty-eight individuals (26 female; mean age, 23.3 ± 8.1 years) were prospectively studied at 3 T. GRAPPATINI was conducted with the same parameters as the 2D-MESE while shortening the acquisition time from 13:18 to 2:27 minutes. The setup was also validated in a phantom experiment using a 6.48-hour-long single echo-spin echo sequence as reference. The IVDs were manually segmented on 4 central slices. The median nucleus pulposus showed a strong Pearson correlation coefficient between T2GRAPPATINI and T2MESE (rp = 0.919; P < 0.001). There was also a significant correlation for the ventral (rp = 0.241; P < 0.001) and posterior (rp = 0.418; P < 0.001) annular regions.In the single spin-echo phantom experiment, the most accurate T2 estimation was achieved using T2GRAPPATINI with a median absolute deviation of 15.3 milliseconds as compared with T2MESE with 26.5 milliseconds. GRAPPATINI facilitates precise T2 mapping at 3 T in accordance with clinical standards and reference methods using the same parameters while shortening acquisition times from 13:18 to 2:27 minutes with the same parameters.

Structure and Role of BCOR PUFD in Noncanonical PRC1 Assembly and Disease.

Polycomb repression complex 1 (PRC1) is a multiprotein assembly that regulates transcription. The Polycomb group ring finger 1 protein (PCGF1) is central in the assembly of the noncanonical PRC1 variant called PRC1.1 through its direct interaction with BCOR (BCL-6-interacting corepressor) or its paralog, BCOR-like 1 (BCORL1). Previous structural studies revealed that the C-terminal PUFD domain of BCORL1 is necessary and sufficient to heterodimerize with the RAWUL domain of PCGF1 and, together, form a new protein-protein binding interface that associates with the histone demethylase KDM2B. Here, we show that the PUFD of BCOR and BCORL1 differ in their abilities to assemble with KDM2B. Unlike BCORL1, the PUFD of BCOR alone does not stably assemble with KDM2B. Rather, additional residues N-terminal to the BCOR PUFD are necessary for stable association. Nuclear magnetic resonance (NMR) structure determination and 15N T2 relaxation time measurements of the BCOR PUFD alone indicate that the termini of the BCOR PUFD, which are critical for binding PCGF1 and KDM2B, are disordered. This suggests a hierarchical mode of assembly whereby BCOR PUFD termini become structurally ordered upon binding PCGF1, which then allows stable association with KDM2B. Notably, BCOR internal tandem duplications (ITDs) leading to pediatric kidney and brain tumors map to the PUFD termini. Binding studies with the BCOR ITD indicate the ITD would disrupt PRC1.1 assembly, suggesting loss of the ability to assemble PRC1.1 is a critical molecular event driving tumorigenesis.

Verification of Nuclear Magnetic Resonance Characterization of Traditional Homeopathically Manufactured Metal (Cuprum metallicum) and Plant (Gelsemium sempervirens) Medicines and Controls.

Nuclear magnetic resonance (NMR) proton relaxation is sensitive to the dynamics of the water molecule, H2O, through the interaction of the spin of the proton (1H) with external magnetic and electromagnetic fields. NMR relaxation times describe how quickly the spin of 1H, forced in a direction by an external electromagnetic field, returns to a normal resting position. As a result, such measurements allow us potentially to describe higher structuring of water in homeopathic medicines. The purpose of the present study was to verify whether specific NMR relaxation times could be measured in full lines of cH dynamizations of a metal (copper) and of a plant substance (Gelsemium sempervirens), compared with a solvent control, a potentized lactose control and a control prepared by simple dilution, in three production lines. It is aimed at verification of a previous publication (2017) on two new manufacturing lines of the same starting material and controls. To monitor dilution and potentization processes, measurements of 1H spin-lattice T1 and spin-spin T2 relaxation times were used. T1 and T2 relaxation times were measured at 25°C with a spin analyser working at a frequency of 20 MHz. To account for its possible role as a confounding factor, free oxygen was also measured in all samples, using a MicroOptode meter. When the values of the three production lines were pooled, a statistically significant discrimination of NMR relaxation times between the medicines and their controls was confirmed. We found for copper cH and Gelsemium sempervirens cH a highly significant influence of the starting material (p = 0.008), a highly significant influence of level of dilution (p < 0.001), and a significant influence of the O2 concentration (p = 0.04). We have evidence of an obvious retention of a specific magnetic resonance signal when a substance (lactose, copper, Gelsemium) is diluted/potentized in pure water. This means that homeopathic solutions cannot be considered to be pure water. O2 is a covariant and not an explanatory variable: this factor itself is too weak to explain the NMR signal specificities in potentized samples. Homeopathic dilutions may thus have a specific material configuration governed not only by the potentized substance but also by the chemical nature of the containers, the chemical nature of dissolved gases and even by the electromagnetic environment. This sensitivity of homeopathically prepared medicines to electromagnetic fields may be amplified by the processes routinely applied during their preparation; because it occurs only when a dynamization has been performed, we may call this phenomenon "dynamic pharmacy".

Assessment of spin-lattice T1 and spin-spin T2 relaxation time measurements in breast cell cultures at 1.5 Tesla as a potential diagnostic tool in vitro

Magnetic resonance imaging (MRI) is a critically important tool in current medicine. This dynamic diagnostic method allows for detailed and accurate imaging of the human body and diagnosis of metabolic changes by magnetic resonance spectroscopy (MRS) assays. Our work presented herein shows measurement of spin-lattice T1 and spin-spin T2 relaxation time as an indicator of changes in cellular morphology. MRI spin-lattice T1 and spin-spin T2 relaxation time measurements are innovative experiments that provide a detailed picture of the biological microenvironment within cell cultures. Here, we used two types of cell cultures: cancerous and healthy breast cells. By measuring spin-lattice T1 and spin-spin T2 relaxation time in cancerous and healthy cell cultures we can detect differences and morphological conditions of both cell lines. A number of observations indicate that MRI can detect differences between cancer and healthy cells. In order to obtain a high density of cells for our cellular MRI study, we grew the cells in 3D geometry. In this paper, we underline the potential of quantitative MRI in vitro for future cellular mapping of drug concentration and drug efficiency in cell culture. We have shown that MRI, which is used often for imaging of anatomy, is also a promising technology for specific morphological measurements of cells.

A novel anthropomorphic multimodality phantom for MRI-based radiotherapy quality assurance testing.

Increased utilization of magnetic resonance imaging (MRI) in radiotherapy has caused a growing need for phantoms that provide tissue-like contrast in both computed tomography (CT) and MRI images. Such phantoms can be used to compare MRI-based processes with CT-based clinical standards. Here, we develop and demonstrate the clinical utility of a three-dimensional (3D)-printed anthropomorphic pelvis phantom containing materials capable of T1 , T2 , and electron density matching for a clinically relevant set of soft tissues and bone. The phantom design was based on a male pelvic anatomy template with thin boundaries separating tissue types. Slots were included to allow insertion of various dosimeters. The phantom structure was created using a 3D printer. The tissue compartments were filled with carrageenan-based materials designed to match the T1 and T2 relaxation times and electron densities of the corresponding tissues. CT and MRI images of the phantom were acquired and used to compare phantom T1 and T2 relaxation times and electron densities to literature-reported values for human tissue. To demonstrate clinical utility, the phantom was used for end-to-end testing of an MRI-only treatment simulation and planning workflow. Based on a T2 -weighted MRI image, synthetic CT (sCT) images were created using a statistical decomposition algorithm (MRIPlanner, Spectronic Research AB, Sweden) and used for dose calculation of volumetric-modulated arc therapy (VMAT) and seven-field intensity-modulated radiation therapy (IMRT) prostate plans. The plans were delivered on a Truebeam STX (Varian Medical Systems, Palo Alto, CA), with film and a 0.3cc ion chamber used to measure the delivered dose. Doses calculated on the CT and sCTs were compared using common dose volume histogram metrics. T1 and T2 relaxation time and electron density measurements for the muscle, prostate, and bone agreed well with literature-reported in vivo measurements. Film analysis resulted in a 99.7% gamma pass rate (3.0%, 3.0mm) for both plans. The ion chamber-measured dose discrepancies at the isocenter were 0.36% and 1.67% for the IMRT and VMAT plans, respectively. The differences in PTV D98% and D95% between plans calculated on the CT and 1.5T/3.0T-derived sCT images were under 3%. The developed phantom provides tissue-like contrast on MRI and CT and can be used to validate MRI-based processes through comparison with standard CT-based processes.

NMR Relaxation Measurements on Complex Samples Based on Real-Time Pure Shift Techniques.

Longitudinal spin-lattice relaxation (T1) and transverse spin-spin relaxation (T2) reveal valuable information for studying molecular dynamics in NMR applications. Accurate relaxation measurements from conventional 1D proton spectra are generally subject to challenges of spectral congestion caused by J coupling splittings and spectral line broadenings due to magnetic field inhomogeneity. Here, we present an NMR relaxation method based on real-time pure shift techniques to overcome these two challenges and achieve accurate measurements of T1 and T2 relaxation times from complex samples that contain crowded NMR resonances even under inhomogeneous magnetic fields. Both theoretical analyses and detailed experiments are performed to demonstrate the effectiveness and ability of the proposed method for accurate relaxation measurements on complex samples and its practicability to non-ideal magnetic field conditions.