Myocardial T1 mapping and determination of partition coefficients at 3 tesla: comparison between gadobenate dimeglumine and gadofosveset trisodium.

OBJECTIVE: To compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient. MATERIALS AND METHODS: Study subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1. RESULTS: A total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being -7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate. CONCLUSION: Myocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.

Myocardial T1 mapping and determination of partition coefficients at 3 tesla: comparison between gadobenate dimeglumine and gadofosveset trisodium / Mapa T1 e coeficiente de partição do miocárdio em aparelho 3 tesla: comparação entre gadobenato de dimeglumina e gadofosveset trissódico

Abstract Objective: To compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient. Materials and Methods: Study subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1. Results: A total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being −7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate. Conclusion: Myocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.

Resumo Objetivo: Avaliar o efeito da utilização de um agente de contraste intravascular baseado em gadolínio quelado a albumina (gadofosveset) no tempo T1 e no coeficiente de partição do miocárdio, quando comparado com um agente de contraste extravascular baseado no gadolínio não quelado a albumina (gadobenato). Materiais e Métodos: Os participantes do estudo foram submetidos a dois exames para aquisições do mapeamento T1 em aparelho de 3 tesla. Utilizando uma sequência de pulso modificada - modified look-locker inversion recovery (MOLLI) -, realizou-se uma etapa pré-contraste e duas etapas pós-contraste do mapa T1 (média de 15 e 21 minutos). O coeficiente de partição foi calculado como: ΔR1miocárdio /ΔR1sangue. Resultados: Um total de 252 valores de mapa T1 no miocárdio e no sangue foi obtido em 21 indivíduos saudáveis. Após a administração do meio de contraste, a diferença média do tempo T1 do miocárdio entre os agentes de contraste foi -7,6 ± 60 ms (p = 0,41) (isto é, gadobenato T1 < gadofosveset T1). Já no sangue, a diferença média de tempo T1 foi 56,5 ± 67 ms (p < 0,001) (isto é, gadobenato T1 > gadofosveset T1). O coeficiente de partição foi maior para o gadobenato (λ = 0,41) do que para o gadofosveset (λ = 0,33), refletindo uma eliminação mais lenta do gadofosveset em comparação com o gadobenato. Conclusão: Os tempos T1 do miocárdio não foram significativamente diferentes entre gadobenato e gadofosveset. Os coeficientes de partição foram significativamente mais baixos para o agente de contraste intravascular em comparação com o agente extravascular em doses clínicas típicas de cada contraste.

Part 2 - Coronary angiography with gadofosveset trisodium: a prospective intra-subject comparison for dose optimization for 100 % efficiency imaging.

BACKGROUND: Three tesla (3T) coronary magnetic resonance angiography (MRA) may be optimized using gadolinium-based contrast agents (GBCA) such as gadofosveset trisodium. The goal of this study was to evaluate if there is a qualitative or quantitative improvement in the coronary arteries with variation in contrast dose. METHODS: Twenty-eight healthy volunteers were prospectively recruited for coronary MRA at 3T using a steady state injection technique for 3D radial whole-heart image acquisition with retrospective respiratory self-gating (ClinicalTrials.gov identifier: NCT01853592). Nineteen volunteers completed both single- and double-dose imaging instances (0.03 and 0.06 mmol/kg, respectively). Intra-individual comparison of image quality was assessed by measurement of apparent signal/contrast-to-noise ratio (aSNR/aCNR) and subjective evaluation of image quality by 2 independent reviewers. RESULTS: The average duration of coronary MRA acquisition was 7.2 ± 1.2 min. There was significantly higher (60 %, p < 0.001) aSNR of the aorta and right/left ventricle for the double dose compared to single dose injection scheme and aSNR of the coronary arteries increased by 70 % (p < 0.001) for the double dose injection. aCNR increased by +55 % and +60 % in the ventricles and coronary arteries, respectively (p < 0.001). Overall segmental artery visualization for single dose was possible 47 % of the time, which improved to 60 % with double dose (p = 0.019), predominantly driven by improvements in more distal segment visualization (+40 % improvement in mid arterial segments, p = 0.013). CONCLUSIONS: Gadofosveset trisodium dose of 0.06 mmol/kg significantly quantitatively and qualitatively improves the coronary artery image quality compared to 0.03 mmol/kg at 3T for moderate duration (6-8 min) steady state contrast enhanced coronary MRA.

Part 1 - Coronary angiography with gadofosveset trisodium: a prospective feasibility study evaluating injection techniques for steady-state imaging.

BACKGROUND: The purpose of this study was to define an optimal injection protocol for 5-10 min duration navigator-based coronary MR angiography using an intravascular gadolinium-based contrast agent (GBCA), which is better suited for steady-state coronary MR angiography than conventional GBCAs. METHODS: Using projections from pharmacokinetic models of the intravascular concentration of gadofosveset, a dual-injection protocol was formulated and tested on 14 healthy human subjects. Modified Look-Locker inversion recovery (MOLLI) sequences were used for T1 mapping at 3 Tesla to evaluate the concentration of tracer in the aorta over the scanning interval. RESULTS: Pharmacokinetic models for a bolus plus slow infusion technique at a 5, 10, and 15 min steady state intravascular concentration was compared to single bolus curves. The 70 %/30 % bolus/slow infusion technique resulted in the highest intravascular concentration over a 5 min scan duration. Similarly, the 60 %/40 % bolus/slow infusion technique was projected to be ideal for image acquisition duration of 5-10 min. These models were confirmed with T1 maps on normal volunteers. Arterial-venous mixing of contrast was achieved within 90 s of the beginning of the bolus. CONCLUSIONS: Gadofosveset injection is optimized for the lowest intravascular T1 time for 5-10 min duration MR angiography by bolus injection of 60-70 % of the total dose followed by slow infusion of the remainder of the total dose. This protocol achieves rapid and prolonged steady state intravascular concentrations of the GBCA that may be useful for prolonged image acquisition, such as required for navigator-based coronary MR angiography at 3 Tesla. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01130545 NCT01130545 , registered as of May 25, 2010.

Regional Strain Analysis with Multidetector CT in a Swine Cardiomyopathy Model: Relationship to Cardiac MR Tagging and Myocardial Fibrosis.

PURPOSE: To investigate the use of cine multidetector computed tomography (CT) to detect changes in myocardial function in a swine cardiomyopathy model. MATERIALS AND METHODS: All animal protocols were in accordance with the Principles for the Utilization and Care of Vertebrate Animals Used in Testing Research and Training and approved by the University of Missouri Animal Care and Use Committee. Strain analysis of cine multidetector CT images of the left ventricle was optimized and analyzed with feature-tracking software. The standard of reference for strain was harmonic phase analysis of tagged cardiac magnetic resonance (MR) images at 3.0 T. An animal model of cardiomyopathy was imaged with both cardiac MR and 320-section multidetector CT at a temporal resolution of less than 50 msec. Three groups were evaluated: control group (n = 5), aortic-banded myocardial hypertrophy group (n = 5), and aortic-banded and cyclosporine A- treated cardiomyopathy group (n = 5). Histologic samples of the myocardium were obtained for comparison with strain results. Dunnett test was used for comparisons of the concentric remodeling group and eccentric remodeling group against the control group. RESULTS: Collagen volume fraction ranged from 10.9% to 14.2%; lower collagen fraction values were seen in the control group than in the cardiomyopathy groups (P < .05). Ejection fraction and conventional metrics showed no significant differences between control and cardiomyopathy groups. Radial strain for both cardiac MR and multidetector CT was abnormal in both concentric (cardiac MR 25.1% ± 4.2; multidetector CT 28.4% ± 2.8) and eccentric (cardiac MR 23.2% ± 2.0; multidetector CT 24.4% ± 2.1) remodeling groups relative to control group (cardiac MR 18.9% ± 1.9, multidetector CT 22.0% ± 1.7, P < .05, all comparisons). Strain values for multidetector CT versus cardiac MR showed better agreement in the radial direction than in the circumferential direction (r = 0.55, P = .03 vs r = 0.40, P = .13, respectively). CONCLUSION: Multidetector CT strain analysis has potential to identify regional wall-motion abnormalities in cardiomyopathy that is not otherwise detected using conventional metrics of myocardial function.

Modified look-locker inversion recovery T1 mapping indices: assessment of accuracy and reproducibility between magnetic resonance scanners.

BACKGROUND: Cardiovascular magnetic resonance (CMR) T1 mapping indices, such as T1 time and partition coefficient (λ), have shown potential to assess diffuse myocardial fibrosis. The purpose of this study was to investigate how scanner and field strength variation affect the accuracy and precision/reproducibility of T1 mapping indices. METHODS: CMR studies were performed on two 1.5T and three 3T scanners. Eight phantoms were made to mimic the T1/T2 of pre- and post-contrast myocardium and blood at 1.5T and 3T. T1 mapping using MOLLI was performed with simulated heart rate of 40-100 bpm. Inversion recovery spin echo (IR-SE) was the reference standard for T1 determination. Accuracy was defined as the percent error between MOLLI and IR-SE, and scan/re-scan reproducibility was defined as the relative percent mean difference between repeat MOLLI scans. Partition coefficient was estimated by ΔR1myocardium phantom/ΔR1blood phantom. Generalized linear mixed model was used to compare the accuracy and precision/reproducibility of T1 and λ across field strength, scanners, and protocols. RESULTS: Field strength significantly affected MOLLI T1 accuracy (6.3% error for 1.5T vs. 10.8% error for 3T, p<0.001) but not λ accuracy (8.8% error for 1.5T vs. 8.0% error for 3T, p=0.11). Partition coefficients of MOLLI were not different between two 1.5T scanners (47.2% vs. 47.9%, p=0.13), and showed only slight variation across three 3T scanners (49.2% vs. 49.8% vs. 49.9%, p=0.016). Partition coefficient also had significantly lower percent error for precision (better scan/re-scan reproducibility) than measurement of individual T1 values (3.6% for λ vs. 4.3%-4.8% for T1 values, approximately, for pre/post blood and myocardium values). CONCLUSION: Based on phantom studies, T1 errors using MOLLI ranged from 6-14% across various MR scanners while errors for partition coefficient were less (6-10%). Compared with absolute T1 times, partition coefficient showed less variability across platforms and field strengths as well as higher precision.

3.0-T whole-heart coronary magnetic resonance angiography: comparison of gadobenate dimeglumine and gadofosveset trisodium.

Gadolinium enhanced coronary magnetic resonance angiography (MRA) at 3 T appears to be superior to non-contrast methods. Gadofosveset is an intravascular contrast agent that may be well suited to this application. The purpose of this study was to perform an intra-individual comparison of gadofosveset and gadobenate for coronary MRA at 3 T. In this prospective randomized study, 22 study subjects [8 (36%) male; 27.9 ± 6 years; BMI = 22.8 ± 2 kg/m(2)] underwent two studies using a contrast-enhanced inversion recovery three-dimensional fast low angle shot MRA at 3 T. The order of contrast agent administration was varied randomly, separated by an average of 30 ± 5 days, using either gadobenate dimeglumine (Gd-BOPTA; Bracco, 0.1 mmol/Kg) or gadofosveset trisodium (MS-325; Lantheus Med, 0.03 mmol/Kg). Acquisition time, signal-to-noise ratio (SNR) of coronary vessels and contrast-to-noise ratio (CNR) were evaluated. Of 308 coronary arteries and veins segment analyzed, overall SNR of coronary arteries and veins segments were not different for the two contrast agents (132 ± 79 for gadofosveset vs. 135 ± 78 for gadobenate, p = 0.69). Coronary artery CNR was greater for gadofosveset in comparison to gadobenate (73.5 ± 46.9 vs. 59.3 ± 75.7 respectively, p = 0.03). Gadofosveset-enhanced MRA images displayed better image quality than gadobenate-enhanced MRA images (2.77 ± 0.61 for gadofosveset vs. 2.11 ± 0.51, p < .001). Inter- and intra-reader variability was excellent (ICC > 0.90) for both contrast agents. Gadofosveset trisodium appears to show slightly better performance for coronary MRA at 3 T compared to gadobenate.