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PURPOSE: This study assessed the clinical classification performance of an R2*-based MRI technique for LIC quantification relative to FerriScan, with intra-patient FerriScan LIC uncertainty taken into account. The variabilities of R2* and FerriScan LIC were also assessed. MATERIALS AND METHODS: This was an ethics approved retrospective study, performed on patients undergoing chelation treatment for iron overload. 126 patients (69 women, 57 men), with an age of 42 +/- 16 years (range 19-86 years) were included. FerriScan and R2* MRI at 1.5 T were performed as part of a routine liver iron assessment protocol. For R2* MRI, a commercially available pulse sequence and reconstruction implementation was used, together with a previously derived calibration curve to convert R2* to LIC. Clinical classifications arising from R2*-derived LIC estimates were compared to those based on FerriScan. The accuracy and precision of the R2* technique was calculated. The variabilities of FerriScan- and R2*-derived estimates of LIC were compared with a Wilcoxon Signed Rank test. Significance was set at the 95% confidence level. RESULTS: The precision of R2* ranged from 0.59 to 0.92, with an overall accuracy of 72%. When intra-patient FerriScan LIC uncertainty was considered, precision and accuracy increased to >94% and 97% respectively. The R2*-LIC variability (=17%) was significantly lower than the FerriScan-LIC variability (34%) at the 95% confidence level (p < 10-3). CONCLUSION: MRI R2*-based LIC estimates provided a similar clinical classification as FerriScan. The intra-patient uncertainty of R2*-based LIC estimates was significantly lower than FerriScan.
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OBJECTIVE: Conventional single-echo spin-echo T2 mapping used for liver iron quantification is too long for breath-holding. This study investigated a short TR (~100 ms) single-echo spin-echo T2 mapping technique wherein each image (corresponding to a single TE) could be acquired in ~17 s-short enough for a breath-hold. TE images were combined for T2 fitting. To avoid T1 bias, each TE acquisition incremented TR to maintain a constant TR-TE. MATERIALS AND METHODS: Experiments at 1.5T validated the technique's accuracy in phantoms, 9 healthy volunteers, and 5 iron overload patients. In phantoms and healthy volunteers, the technique was compared to the conventional approach of constant TR for all TEs. Iron overload results were compared to FerriScan. RESULTS: In phantoms, the constant TR-TE technique provided unbiased estimates of T2, while the conventional constant TR approach underestimated it. In healthy volunteers, there was no significant discrepancy at the 95% confidence level between constant TR-TE and reference T2 values, whereas there was for constant TR scans. In iron overload patients, there was a high correlation between constant TR-TE and FerriScan T2 values (r2 = 0.95), with a discrepancy of 0.6+/- 1.4 ms. DISCUSSION: The short-TR single-echo breath-hold spin-echo technique provided unbiased estimates of T2 in phantoms and livers.
Subject(s)
Iron Overload , Liver , Humans , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Breath Holding , Iron , Iron Overload/diagnostic imagingABSTRACT
Background: In hemophilia, recurrent hemarthrosis may lead to irreversible arthropathy. T2 mapping MRI may reflect cartilage changes at an earlier reversible stage of arthropathy as opposed to structural MRI. Objectives: To evaluate interval changes of T2 mapping compared with the International Prophylaxis Study Group (IPSG) structural MRI scores of ankle cartilage in boys with hemophilia receiving prophylaxis. Methods: Eight boys with hemophilia A (median age, 13; range, 9-17 years), 7 age- and sex-matched healthy boys (controls, median age, 15; range, 7-16 years). A multiecho spin-echo T2-weighted MRI sequence at 3.0T was used to obtain T2 maps of cartilage of boys with hemophilia and controls. Structural joint status was evaluated using the IPSG MRI score. Results: T2 relaxation times of ankle cartilage increased significantly over time in both persons with hemophilia and controls (P = .002 and P = .00009, respectively). Changes in T2 relaxation time strongly correlated with changes in IPSG cartilage scores (rs = 0.93 to rs = 0.78 [P = .0007 to P = .023]), but not with changes in age (P = .304 to P = .840). Responsiveness of T2 relaxation times were higher than that of IPSG cartilage scores, with standardized response means >1.4 for T2 mapping in all regions-of-interest compared with 0.84 for IPSG cartilage scores. Baseline T2 relaxation time strongly correlated with timepoint 2 IPSG cartilage score (rs = 0.93 to rs = 0.82 [P = .001 to P = .012]) and T2 relaxation time (rs = 0.98 to rs = 0.88 [P = .00003 to P = .004]) changes in most regions-of-interest. Conclusion: T2 mapping shows sensitivity to biochemical changes in cartilage prior to detectable damage using conventional MRI, offering potential for early detection of bleed-related cartilage damage in boys with hemophilia.
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Importance: There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). Objective: To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. Design, Setting, and Participants: This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Exposures: Sequential therapy with anthracyclines, trastuzumab, and radiation. Main Outcomes and Measures: CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Results: Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. Conclusions and Relevance: In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.
Subject(s)
Breast Neoplasms , Heart Diseases , Hyperemia , Humans , Female , Middle Aged , Cardiotoxicity/diagnostic imaging , Cardiotoxicity/etiology , Breast Neoplasms/drug therapy , Cohort Studies , Contrast Media , Prospective Studies , Gadolinium , Magnetic Resonance Imaging, Cine , Trastuzumab/adverse effects , Heart Diseases/diagnosis , Heart Diseases/diagnostic imaging , Fibrosis , Receptor, ErbB-2 , Anthracyclines/adverse effects , Magnetic Resonance Spectroscopy , InflammationABSTRACT
BACKGROUND: Persons with hemophilia experience hemarthrosis, which can lead to cartilage degeneration, causing physical impairment. MRI T2 mapping has the potential to be used as a tool to evaluate early arthropathic changes and cartilage degeneration in patients with hemophilia. PURPOSE: To assess the value of MRI-T2 mapping as a tool for investigating the cartilage status of children and adolescents with hemophilic arthropathy. STUDY TYPE: Prospective, cross-sectional. SUBJECTS: Twenty-eight boys with hemophilia (aged 5-17 years) and 23 healthy boys (aged 7-17 years). FIELD STRENGTH/SEQUENCES: A multiecho spin-echo T2 -weighted gradient echo sequence was used on a 3.0T magnet. ASSESSMENT: MRI-T2 maps of ankle (tibia-talus) (n = 19) or knee (femur-tibia) (n = 9) cartilage were assessed in hemophilia and healthy groups. An anatomically-based MRI score was also assigned to each ankle/knee. STATISTICAL TESTS: Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC), and analysis of variance (ANOVA) test. RESULTS: Negative associations between age and ankle/knee cartilage T2 relaxation times were found in hemophilia (r = -0.72 [P = 0.03] to -0.55 [P = 0.01]) and healthy (r = -0.84 [P < 0.001] to -0.55 [P = 0.20]) groups. There were nonsignificant associations between ankle cartilage T2 relaxation times and MRI scores (r = -0.15 [P = 0.54] to 0.31 [P = 0.19]). DATA CONCLUSION: Results of this clinical investigation emphasize the potential importance of MRI-T2 maps as a tool to understand the functional status of cartilage in children and adolescents with hemophilic arthropathy, while holding promise for the detection of early cartilage degeneration prior to macroscopic characterization by conventional MRI. MRI-T2 mapping may provide novel information that is not reflected in the anatomically-based MRI scoring system. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
Subject(s)
Cartilage, Articular , Adolescent , Cartilage, Articular/diagnostic imaging , Child , Child, Preschool , Cross-Sectional Studies , Humans , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging , Male , Prospective StudiesABSTRACT
BACKGROUND: Investigation of a simple, precision optimized, identical pre-/post-contrast modified look locker inversion recovery (MOLLI) protocol employing Composite inversion group (IG) fitting in a clinical cardiomyopathy population. METHODS: Cardiac magnetic resonance imaging (MRI) was performed at 3 Tesla in 36 patients (48.0 years [IQR: 35.7, 58.2 years]) with known/suspicion of hypertrophic cardiomyopathy. T1 mapping was performed pre-/post-contrast (0.15 mmol/kg Gadobutrol) using a standard 3-parameter fit (STANDARD) and an optimized (OPTIMAL) single-protocol Composite-IG fitting MOLLI approach. The OPTIMAL protocol was based on a simulation study (for 11hb acquisitions) with cost metric analysis across the range of expected T1 values (300-1400 ms) and heart rates (50-80 bpm). All maps were generated offline based on motion corrected source images. Based on region of interest analysis, the precision of both approaches was assessed using a previously validated propagation of errors technique for pre-/post-contrast T1 mapping as well as calculated ECV (based on point-of care hematocrit measurements. Furthermore, respective T1 and ECV values were calculated. Statistical methods included Wilcoxon Signed-Rank tests and Student's paired t-test. RESULTS: A total of ~9000 11hb inversion groupings were simulated with a 4(0)2(0)2(0)2(0)1 grouping providing the optimal precision across the specified T1/heart rate range. In comparison to standard pre-contrast 5(3)3 MOLLI, this OPTIMAL protocol demonstrated a significantly improved pre-contrast precision (9.1 [6.2, 9.9]ms vs. 9.4 [7.3, 10.8]ms; P < 0.001) while no significant differences were found for post-contrast T1 mapping (4.5 [2.6, 5.3]ms vs. 4.2 [2.8, 5.1]ms; P = 0.25) and EVC mapping (0.38 [0.28, 0.45]ms vs. 0.35 [0.25, 0.44]ms; P = 0.07) or reproducibility (0.16 [0.14, 0.19] vs. 0.19 [0.13, 0.23]P = 0.53). Direct comparison of resulting T1/ECV values demonstrated no significant differences between STANDARD and OPTIMAL techniques for pre-contrast T1 (1178 [1158, 1199]ms vs. 1173 [1143, 1195]ms; P = 0.46) and significant differences for post-contrast T1 (466 [446, 506]ms vs. 456 [433, 503]ms; P = 0.04) and ECV (23.1 [20.8, 25.1]% vs. 23.9 [22.3, 26.4]%; P = 0.001). CONCLUSIONS: A single optimized Composite-IG fitting protocol for pre-/post-contrast T1 mapping demonstrated improved precision over standard MOLLI techniques. It enables a simplified workflow with reduction of potential sources of error especially with respect to image data co-registration easing advanced post-processing for generation of patient specific ECV maps.
Subject(s)
Contrast Media , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging , Adult , Artifacts , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Computer Simulation , Female , Heart/diagnostic imaging , Heart/physiopathology , Humans , Male , Movement , Organometallic Compounds , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
OBJECTIVES: The purpose of this study was to compare clinical decision-making in iron overload patients using FerriScan and an R2*-based approach. METHODS: One-hundred and six patients were imaged at two consecutive timepoints (454 ± 158 days) on a 1.5-T Siemens MAGNETOM Avanto Fit scanner. For both timepoints, patients underwent the standard FerriScan MRI protocol. During the second exam, each patient additionally underwent R2*-MRI mapping. For each patient, a retrospective (simulated) decision was made to increase, decrease, or maintain chelator levels. Two different decision models were considered: The fixed threshold model assumed that chelator adjustments are based strictly on fixed liver iron concentration (LIC) thresholds. Decisions made with this model depend only on the most recent LIC value and do not require any clinician input. The second model utilized decisions made by two hematologists retrospectively based on trends between two consecutive LIC values. Agreement (κA) between hematologists (i.e., interobserver variability) was compared with the agreement (κB) between a single hematologist using the two different LIC techniques. RESULTS: Good agreement between R2*- and FerriScan-derived decisions was achieved for the fixed threshold model. True positive/negative rates were greater than 80%, and false positive/negative rates were less than 10%. ROC analysis yielded areas under the curve greater than 0.95. In the second model, the agreement in clinical decision-making for the two scenarios (κA vs. κB) was equal at the 95% confidence level. CONCLUSIONS: Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another. KEY POINTS: ⢠Good agreement between R2*- and FerriScan-derived decisions in liver iron overload patient management ⢠Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another.
Subject(s)
Clinical Decision-Making , Iron Overload/diagnosis , Iron/metabolism , Liver/metabolism , Magnetic Resonance Imaging/methods , Adult , Aged , Female , Humans , Iron Overload/metabolism , Liver/diagnostic imaging , Male , Middle Aged , ROC Curve , Retrospective Studies , Young AdultABSTRACT
OBJECTIVES: The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T1, T2, and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD). BACKGROUND: Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability. METHODS: A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T1 and T2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM. RESULTS: Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T1 (29 ms), T2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T1. The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%). CONCLUSIONS: The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.
Subject(s)
Anthracyclines/adverse effects , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Heart Diseases/diagnostic imaging , Magnetic Resonance Imaging, Cine , Trastuzumab/adverse effects , Adult , Biomarkers/blood , Cardiotoxicity , Case-Control Studies , Female , Heart Diseases/blood , Heart Diseases/chemically induced , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Observer Variation , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Time Factors , Troponin I/bloodABSTRACT
The accumulation of INTERmuscular fat and INTRAmuscular fat (IMF) has been a hallmark of individuals with diabetes, those with mobility impairments such as spinal cord injuries and is known to increase with aging. An elevated amount of IMF has been associated with fractures and frailty, but the imprecision of IMF measurement has so far limited the ability to observe more consistent clinical associations. Magnetic resonance imaging has been recognized as the gold standard for portraying these features, yet reliable methods for quantifying IMF on magnetic resonance imaging is far from standardized. Previous investigators used manual segmentation guided by histogram-based region-growing, but these techniques are subjective and have not demonstrated reliability. Others applied fuzzy classification, machine learning, and atlas-based segmentation methods, but each is limited by the complexity of implementation or by the need for a learning set, which must be established each time a new disease cohort is examined. In this paper, a simple convergent iterative threshold-optimizing algorithm was explored. The goal of the algorithm is to enable IMF quantification from plain fast spin echo (FSE) T1-weighted MR images or from water-saturated images. The algorithm can be programmed into Matlab easily, and is semiautomated, thus minimizing the subjectivity of threshold-selection. In 110 participants from 3 cohort studies, IMF area measurement demonstrated a high degree of reproducibility with errors well within the 5% benchmark for intraobserver, interobserver, and test-retest analyses; in contrast to manual segmentation which already yielded over 20% error for intraobserver analysis. This algorithm showed validity against manual segmentations (r > 0.85). The simplicity of this technique lends itself to be applied to fast spin echo images commonly ordered as part of standard of care and does not require more advanced fat-water separated images.
Subject(s)
Adipose Tissue/diagnostic imaging , Magnetic Resonance Imaging/methods , Muscle, Skeletal/diagnostic imaging , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged , Reproducibility of Results , Subcutaneous Fat/diagnostic imaging , Young AdultABSTRACT
A technique is presented for performing T2 spectroscopy in magnetic resonance imaging (MRI). It is based on a weighted linear combination of T2 decay data. The data is combined in a manner that acts like a filter on the T2 spectrum. The choice of weighting coefficients determines the filter specifications (e.g. passband/stopband locations, stopband suppression factors). To perform spectroscopy, a series of filters are designed with narrow passbands centered about consecutive regions of the T2 spectrum. This provides an estimate of every region of the spectrum. Taken together, an initial estimate of the full T2 spectrum is thus obtained. However, the filtering process causes a distortion of the estimate relative to the true spectrum. To reduce this distortion, deconvolution is performed. The characteristics of the technique are first evaluated through simulation. The technique is then applied to experimental MRI data to demonstrate practical feasibility. T2 spectroscopy falls into a class of problems requiring inverse transformation with a set of exponential basis functions (i.e. the Laplace Transform). It is demonstrated how the present technique may be applied to problems involving non-exponential basis functions as well.
Subject(s)
Magnetic Resonance Spectroscopy/methods , Signal Processing, Computer-Assisted , Feasibility Studies , Phantoms, ImagingABSTRACT
MOLLI-based T1 mapping has been applied to a variety of cardiac pathologies. However, conventional MOLLI's requirement for rest periods between inversion groups increases scan time, and limits the choice of inversion groups. The recently developed inversion group (IG) fitting technique eliminates the rest period requirement, and permits complete flexibility of inversion groups. However, a limitation is that its T1 maps have low precision - up to 30% poorer than conventional 3-parameter methods. In the original IG method, T1 maps were derived from the first inversion group only. In the present study, a technique is presented which utilize data from all inversion groups to generate T1 maps. It is hypothesized this "composite-IG" fitting method will provided improved prevision over conventional-IG T1 mapping methods. Simulations, phantom, and in vivo experiments on nine clinical cardiac patients (congenital heart disease, ischemic- and non-ischemic cardiomyopathy) were performed. Imaging was performed on a 1.5â¯T Siemens scanner. Myocardial T1 mapping precision and reproducibility were calculated for conventional-IG, composite-IG, and 3-parameter techniques. Precision and reproducibility between the techniques was compared using the Wilcoxon Signed Rank test. Statistical significance was set at the 95% confidence level, with the Bonferroni correction for multiple comparisons employed. Composite-IG improves precision by 16-38% over conventional-IG (pâ¯<â¯0.01). Composite-IG T1 maps provided up to 5% better precision than 3-parameter fits (pâ¯<â¯0.01). Composite-IG had better reproducibility than conventional-IG (pâ¯<â¯0.01). However, there was no significant difference between composite-IG and conventional 5(3)3 3-parameter reproducibility.
Subject(s)
Heart/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging , Myocardial Ischemia/diagnostic imaging , Algorithms , Cardiomyopathies/diagnostic imaging , Computer Simulation , Heart Defects, Congenital/diagnostic imaging , Humans , Models, Statistical , Monte Carlo Method , Motion , Myocardium/pathology , Phantoms, Imaging , Reproducibility of Results , Software , TimeABSTRACT
Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM-MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient-reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast-enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM-MSCs were characterized by a panel of anti-inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro-inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM-MSC anti-inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM-MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM-MSC dosing and BM-MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757.
Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Osteoarthritis, Knee/therapy , Synovitis/therapy , Biomarkers/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cartilage/metabolism , Cartilage/pathology , Cells, Cultured , Female , Humans , Joint Capsule/metabolism , Joint Capsule/pathology , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Middle Aged , Osteoarthritis, Knee/complications , Quality of Life , Synovitis/etiology , Treatment OutcomeABSTRACT
BACKGROUND: FerriScan is the method-of-choice for noninvasive liver iron concentration (LIC) quantification. However, it has a number of drawbacks including cost and expediency. PURPOSE/HYPOTHESIS: To characterize an R2*-based MRI technique that may potentially be used as an alternative to FerriScan. This was accomplished through the derivation of a calibration curve that characterized the relationship between FerriScan-derived LIC and R2*. The nature and source of uncertainty in this curve were investigated. It was hypothesized that the source of uncertainty is heterogeneity of LIC across the liver. STUDY TYPE: Prospective. SUBJECTS: In all, 125 patients (69 women, 56 men) undergoing chelation treatment for iron overload prospectively underwent FerriScan and R2* MRI during the same exam. FIELD STRENGTH/SEQUENCE: Pulse sequences included 2D multislice spin-echo pulse for FerriScan, and a prototype 3D 6-echo gradient echo acquisition for R2* mapping at 1.5T. ASSESSMENT: A linear calibration curve was derived from the relationship between FerriScan-derived LIC estimates and R2* through least-squares fitting. STATISTICAL TESTS: The nature of the uncertainty in the curve was characterized through tests of normality and homoscedasticity. The source of uncertainty was tested by comparing the magnitude of LIC variation over the FerriScan ROI to the observed uncertainty in the R2*-derived LIC estimates. RESULTS: A linear relationship between logarithmically transformed FerriScan-derived LIC and R2* (log{FerriScan-derived LIC} = 1.029 log{R2*} - 3.822) was confirmed. Uncertainty was random, with a behaviour that was normal and homoscedastic. The source of uncertainty was confirmed as iron heterogeneity across the liver. The nontransformed calibration curve was: FerriScan-derived LIC = 0.0266â R2*, with a constant coefficient-of-variation of 0.32. DATA CONCLUSION: FerriScan and R2* techniques were found to provide equivalent quantification of LIC in this study. Any difference in accuracy or precision was at a level lower than the uncertainty caused by variation in LIC over the liver. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1467-1474.
Subject(s)
Iron Overload/diagnostic imaging , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Aged , Calibration , Female , Humans , Imaging, Three-Dimensional , Iron Overload/etiology , Male , Middle Aged , Prospective Studies , UncertaintyABSTRACT
OBJECTIVES: To evaluate the accuracy of magnetic resonance imaging measurements of cartilage tissue-mimicking phantoms and to determine a combination of magnetic resonance imaging parameters to optimize accuracy while minimizing scan time. METHOD: Edge dimensions from 4 rectangular agar phantoms ranging from 10.5 to 14.5 mm in length and 1.25 to 5.5 mm in width were independently measured by two readers using a steel ruler. Coronal T1 spin echo (T1 SE), fast spoiled gradient-recalled echo (FSPGR) and multiplanar gradient-recalled echo (GRE MPGR) sequences were used to obtain phantom images on a 1.5-T scanner. RESULTS: Inter- and intra-reader reliability were high for both direct measurements and for magnetic resonance imaging measurements of phantoms. Statistically significant differences were noted between the mean direct measurements and the mean magnetic resonance imaging measurements for phantom 1 when using a GRE MPGR sequence (512x512 pixels, 1.5-mm slice thickness, 5:49 min scan time), while borderline differences were noted for T1 SE sequences with the following parameters: 320x320 pixels, 1.5-mm slice thickness, 6:11 min scan time; 320x320 pixels, 4-mm slice thickness, 6:11 min scan time; and 512x512 pixels, 1.5-mm slice thickness, 9:48 min scan time. Borderline differences were also noted when using a FSPGR sequence with 512x512 pixels, a 1.5-mm slice thickness and a 3:36 min scan time. CONCLUSIONS: FSPGR sequences, regardless of the magnetic resonance imaging parameter combination used, provided accurate measurements. The GRE MPGR sequence using 512x512 pixels, a 1.5-mm slice thickness and a 5:49 min scan time and, to a lesser degree, all tested T1 SE sequences produced suboptimal accuracy when measuring the widest phantom.
Subject(s)
Cartilage/diagnostic imaging , Dimensional Measurement Accuracy , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Observer Variation , Radiographic Image Interpretation, Computer-Assisted , Reference Values , Reproducibility of Results , Signal-To-Noise Ratio , Time FactorsABSTRACT
OBJECTIVES: To evaluate the accuracy of magnetic resonance imaging measurements of cartilage tissue-mimicking phantoms and to determine a combination of magnetic resonance imaging parameters to optimize accuracy while minimizing scan time. METHOD: Edge dimensions from 4 rectangular agar phantoms ranging from 10.5 to 14.5 mm in length and 1.25 to 5.5 mm in width were independently measured by two readers using a steel ruler. Coronal T1 spin echo (T1 SE), fast spoiled gradient-recalled echo (FSPGR) and multiplanar gradient-recalled echo (GRE MPGR) sequences were used to obtain phantom images on a 1.5-T scanner. RESULTS: Inter- and intra-reader reliability were high for both direct measurements and for magnetic resonance imaging measurements of phantoms. Statistically significant differences were noted between the mean direct measurements and the mean magnetic resonance imaging measurements for phantom 1 when using a GRE MPGR sequence (512x512 pixels, 1.5-mm slice thickness, 5:49 min scan time), while borderline differences were noted for T1 SE sequences with the following parameters: 320x320 pixels, 1.5-mm slice thickness, 6:11 min scan time; 320x320 pixels, 4-mm slice thickness, 6:11 min scan time; and 512x512 pixels, 1.5-mm slice thickness, 9:48 min scan time. Borderline differences were also noted when using a FSPGR sequence with 512x512 pixels, a 1.5-mm slice thickness and a 3:36 min scan time. CONCLUSIONS: FSPGR sequences, regardless of the magnetic resonance imaging parameter combination used, provided accurate measurements. The GRE MPGR sequence using 512x512 pixels, a 1.5-mm slice thickness and a 5:49 min scan time and, to a lesser degree, all tested T1 SE sequences produced suboptimal accuracy when measuring the widest phantom.
Subject(s)
Cartilage/diagnostic imaging , Dimensional Measurement Accuracy , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Observer Variation , Radiographic Image Interpretation, Computer-Assisted , Reference Values , Reproducibility of Results , Signal-To-Noise Ratio , Time FactorsABSTRACT
Susceptibility-weighted imaging (SWI) has become an important imaging sequence in the evaluation of patients with neurovascular disease. In this review, we provide a general overview of the physics of SWI and describe how image contrast is produced with this technique. We provide a general approach and differential diagnosis for 2 commonly encountered radiographic patterns seen with SWI in neurovascular disease. Finally, we discuss specific neurovascular applications of SWI, including its application in acute stroke, vascular malformations, venous thrombosis, and evaluation of cerebral microbleeds.
Subject(s)
Brain/diagnostic imaging , Cerebrovascular Disorders/diagnostic imaging , Magnetic Resonance Imaging , Brain/pathology , HumansABSTRACT
Purpose To quantify myocardial extracellular volume (ECV) by using cardiac magnetic resonance (MR) imaging in thalassemia major and to investigate the relationship between ECV and myocardial iron overload. Materials and Methods With institutional review board approval and informed consent, 30 patients with thalassemia major (mean age ± standard deviation, 34.6 years ± 9.5) and 10 healthy control subjects (mean age, 31.5 years ± 4.4) were prospectively recruited (clinicaltrials.gov identification number NCT02090699). Nineteen patients (63.3%) had prior myocardial iron overload (defined as midseptal T2* < 20 msec on any prior cardiac MR images). Cardiac MR imaging at 1.5 T included cine steady-state free precession for ventricular function, T2* for myocardial iron quantification, and unenhanced and contrast material-enhanced T1 mapping. ECV was calculated with input of the patient's hematocrit level. Peak systolic global longitudinal strain by means of speckle tracking was assessed with same-day transthoracic echocardiography. Statistical analysis included use of the two-sample t test, Fisher exact test, and Spearman correlation. Results Unenhanced T1 values were significantly lower in patients with prior myocardial iron overload than in control subjects (850.3 ± 115.1 vs 1006.3 ± 35.4, P < .001) and correlated strongly with T2* values (r = 0.874, P < .001). Patients with prior myocardial iron overload had higher ECV than did patients without iron overload (31.3% ± 2.8 vs 28.2% ± 3.4, P = .030) and healthy control subjects (27.0% ± 3.1, P = .003). There was no difference in ECV between patients without iron overload and control subjects (P = .647). ECV correlated with lowest historical T2* (r = -0.469, P = .010) but did not correlate significantly with left ventricular ejection fraction (r = -0.216, P = .252) or global longitudinal strain (r = -0.164, P = .423). Conclusion ECV is significantly increased in thalassemia major and is associated with myocardial iron overload. These abnormalities may potentially reflect diffuse interstitial myocardial fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.
Subject(s)
Heart Diseases/diagnostic imaging , Iron Overload/diagnostic imaging , Magnetic Resonance Imaging , beta-Thalassemia/complications , Adult , Echocardiography , Heart Diseases/etiology , Humans , Iron Overload/etiology , Male , Middle Aged , Myocardium/pathology , beta-Thalassemia/diagnostic imaging , beta-Thalassemia/pathologyABSTRACT
PURPOSE: The Modified Look-Locker Inversion Recovery (MOLLI) technique is used for T1 mapping in the heart. However, a drawback of this technique is that it requires lengthy rest periods in between inversion groupings to allow for complete magnetization recovery. In this work, a new MOLLI fitting algorithm (inversion group [IG] fitting) is presented that allows for arbitrary combinations of inversion groupings and rest periods (including no rest period). THEORY AND METHODS: Conventional MOLLI algorithms use a three parameter fitting model. In IG fitting, the number of parameters is two plus the number of inversion groupings. This increased number of parameters permits any inversion grouping/rest period combination. Validation was performed through simulation, phantom, and in vivo experiments. RESULTS: IG fitting provided T1 values with less than 1% discrepancy across a range of inversion grouping/rest period combinations. By comparison, conventional three parameter fits exhibited up to 30% discrepancy for some combinations. The one drawback with IG fitting was a loss of precision-approximately 30% worse than the three parameter fits. CONCLUSION: IG fitting permits arbitrary inversion grouping/rest period combinations (including no rest period). The cost of the algorithm is a loss of precision relative to conventional three parameter fits. Magn Reson Med 75:2332-2340, 2016. © 2015 Wiley Periodicals, Inc.
Subject(s)
Cardiac Imaging Techniques/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Algorithms , Computer Simulation , Humans , Phantoms, Imaging , Reproducibility of ResultsABSTRACT
PURPOSE: To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy. METHODS AND MATERIALS: We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P<.05. RESULTS: In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina. CONCLUSIONS: Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin.