26 research outputs found
Effectively Measuring Exercise-Related Variations in T1Ï and T2 Relaxation Times of Healthy Articular Cartilage.
BACKGROUND: Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. PURPOSE: To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. STUDY TYPE: Prospective observational study. POPULATION: Phantom and 19 healthy participants. FIELD STRENGTH/SEQUENCE: 3T; 3D fat-saturated spoiled gradient recalled-echo; T1Ï - and T2 -prepared pseudosteady-state 3D fast spin echo. ASSESSMENT: The intrasessional repeatability of T1Ï and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1Ï and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. STATISTICAL TESTS: Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. RESULTS: Without knee repositioning, both surface-averaged T1Ï and T2 were very repeatable on all cartilage surfaces, with RMS-CVâSDD) average exercise-induced in T1Ï and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. DATA CONCLUSION: Joint-loading with a stepping activity resulted in T1Ï and T2 changes above background measurement error. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.GlaxoSmithKline
National Institute of Health Research (NIHR) Cambridge Biomedical Research Centr
Manganese-Enhanced Tâ Mapping in the Myocardium of Normal and Infarcted Hearts
Background. Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods. T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22âÎŒmol/kg)) or chelated (mangafodipir (22â44âÎŒmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100â200âÎŒmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48âh later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Massonâs trichrome (MTC). Results. Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30â43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI â14.8 to 17.1 P>0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI â9.1 to 31.8 P=0.002), as did DEMRI T1 mapping (bias 8.2%, 95% CI â10.7 to 27.2 P=0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial âT1 inversely correlating with left ventricular ejection fraction after myocardial infarction (r=â0.61, P=0.022). Conclusions. MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.</jats:p
Segmentation of knee MRI data with convolutional neural networks for semi-automated three-dimensional surface-based analysis of cartilage morphology and composition
Objective: To assess automatic segmentations for surface-based analysis of cartilage morphology and composition on knee magnetic resonance (MR) images. Methods: 2D and 3D U-Nets were trained on double echo steady state (DESS) images from the publicly available Osteoarthritis Initiative (OAI) dataset with femoral and tibial bone and cartilage segmentations provided by the Zuse Institute Berlin (ZIB). The U-Nets were used to perform automatic segmentation of femoral and tibial bone-cartilage structures (bone and cartilage segmentations combined into one structure) from the DESS images. T2-weighted images from the OAI dataset were registered to the DESS images and used for T2 map calculation. Using the 3D cartilage surface mapping (3D-CaSM) method, surface-based analysis of cartilage morphology (thickness) and composition (T2) was performed using both manual and network-generated segmentations from OAI ZIB testing images. Bland-Altman analyses were performed to evaluate the accuracy of the extracted cartilage thickness and T2 measurements from both U-Nets compared to manual segmentations. Results: Bland-Altman analysis showed a mean bias [95% limits of agreement] for femoral and tibial cartilage thickness measurements ranging between -0.12 to 0.33 [-0.28, 0.96] mm with 2D U-Net and 0.07 to 0.14 [-0.14, 0.39] mm with 3D U-Net. For T2, the mean bias [95% limits of agreement] ranged between -0.16 to 1.32 [-4.71, 4.83] ms with 2D U-Net and -0.05 to 0.46 [-2.47, 3.39] ms with 3D U-Net. Conclusions: While both 2D and 3D U-Nets exemplified the time-efficiency benefit of using deep learning methods for generating the required segmentations, segmentations from 3D U-Nets demonstrated higher accuracy in the extracted thickness and T2 features using 3D-CaSM compared to the segmentations from 2D U-Nets
Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.
BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients receivedââ€â6 monthly doses of dezamizumab in the Phase 2 trial (nâ=â7),ââ€â2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (nâ=â2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)
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Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.
BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients receivedââ€â6 monthly doses of dezamizumab in the Phase 2 trial (nâ=â7),ââ€â2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (nâ=â2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)
Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study
Abstract: Objectives: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. Methods: Fourteen individuals aged 40â60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. Results: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. Conclusions: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. Key Points: âą Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. âą This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. âą The DCE-MRI biomarker Ktransdemonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies
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Quantifying disease activity in rheumatoid arthritis with the TSPO PET ligand 18 F-GE-180 and comparison with 18 F-FDG and DCE-MRI
Abstract: Purpose: While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using 18F-fluorodeoxyglucose (18F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate 18F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared 18F-GE-180 uptake with that of 18F-FDG and DCE-MRI measures of inflammation. Methods: Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with 18F-GE-180 and 18F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUVmax). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient Ktrans using Pearson correlation (r). Results: PET/CT imaging with 18F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). 18F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09â0.31). 18F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUVmax vs. Ktrans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). Conclusions: The correlations between DCE-MRI parameters and 18F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer 18F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA
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Effectively Measuring Exercise-Related Variations in T1Ï and T2 Relaxation Times of Healthy Articular Cartilage.
BACKGROUND: Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. PURPOSE: To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. STUDY TYPE: Prospective observational study. POPULATION: Phantom and 19 healthy participants. FIELD STRENGTH/SEQUENCE: 3T; 3D fat-saturated spoiled gradient recalled-echo; T1Ï - and T2 -prepared pseudosteady-state 3D fast spin echo. ASSESSMENT: The intrasessional repeatability of T1Ï and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1Ï and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. STATISTICAL TESTS: Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. RESULTS: Without knee repositioning, both surface-averaged T1Ï and T2 were very repeatable on all cartilage surfaces, with RMS-CVâSDD) average exercise-induced in T1Ï and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. DATA CONCLUSION: Joint-loading with a stepping activity resulted in T1Ï and T2 changes above background measurement error. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.GlaxoSmithKline
National Institute of Health Research (NIHR) Cambridge Biomedical Research Centr
Magnetic resonance imaging reveals the complementary effects of decongestant and Breathe Right Nasal Strips on internal nasal anatomy
Objectives/Hypothesis
This magnetic resonance imaging (MRI) study of 26 subjects with nasal congestion was performed to assess in the complete nasal passage both the anatomical effect of the marketed Breathe Right Nasal Strip (BRNS) relative to placebo and the potential adjunctive effect of using a decongestant in combination with the BRNS.
Study Design
Randomized, crossover study.
Methods
The study consisted of two parts, the first involving application of either the BRNS or the placebo strip in a randomized, crossover design with evaluator blinding, and repeated MRI scanning; and the second a sequential process of decongestant administration, MRI scanning, application of the BRNS, and repeated MRI. The same anatomical MRI protocol was used throughout. Nasal patency was assessed in the whole nasal passage and eight subregions (by inferiorâsuperior, anteriorâposterior division). Numerical response scores representing subjective nasal congestion were also obtained.
Results
Results demonstrate significant anatomical enlargement with the BRNS relative to placebo (P < .001), as well as an additive effect of using a decongestant in combination with the BRNS; both supported by a strong and significant negative correlation with the subjective nasal response measures of nasal congestion (r = â0.98, P = .002). Furthermore, analysis of the nasal subregions indicates that this adjunctive effect arises from a partially localized action of the complementary products: the BRNS acting primarily anteriorly in the nose and the decongestant mainly posteriorly.
Conclusions
The BRNS alone significantly increases nasal patency and alleviates perceived nasal congestion, and additional relief of symptoms can be obtained with simultaneous use of a decongestant