Fractional myocardial blood volume (fMBV) estimated using ferumoxytol‐enhanced magnetic resonance imaging (MRI) (FE‐MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half‐life and its use for steady‐state MRI is off‐label. The aim of this prospective study was to optimize and evaluate a two‐compartment model for estimation of fMBV based on FE‐MRI. Nine healthy swine and one swine with artificially induced single‐vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin–lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look‐Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125–4.0 mg/kg). fMBV and water exchange were estimated using a two‐compartment model. Model‐fitted fMBV was compared to simple fast‐exchange fMBV approximation and percent change in pre‐ and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one‐way analysis of variance. Fast‐exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland–Altman analysis. Healthy normal swine showed a mean mid‐ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s−1. There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight‐dose and four‐dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement −1.04% [−1.45, −0.62%] to 1.18% [0.77, 1.59%]). Pixel‐wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two‐compartment model based on FE‐MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease. Level of Evidence 2. Technical Efficacy Stage 2.

Purpose To develop a free‐breathing, non‐electrocardiogram technique for simultaneous myocardial T1, T2, T2*, and fat‐fraction (FF) mapping in a single scan. Methods The MR Multitasking framework is adapted to quantify T1, T2, T2*, and FF simultaneously. A variable TR scheme is developed to preserve temporal resolution and imaging efficiency. The underlying high‐dimensional image is modeled as a low‐rank tensor, which allows accelerated acquisition and efficient reconstruction. The accuracy and/or repeatability of the technique were evaluated on static and motion phantoms, 12 healthy volunteers, and 3 patients by comparing to the reference techniques. Results In static and motion phantoms, T1/T2/T2*/FF measurements showed substantial consistency (R > 0.98) and excellent agreement (intraclass correlation coefficient > 0.93) with reference measurements. In human subjects, the proposed technique yielded repeatable T1, T2, T2*, and FF measurements that agreed with those from references. Conclusions The proposed free‐breathing, non‐electrocardiogram, motion‐resolved Multitasking technique allows simultaneous quantification of myocardial T1, T2, T2*, and FF in a single 2.5‐min scan.

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Myocardial T1 reactivity, defined as the relative change in T1 between rest and vasodilator-induced stress, has been proposed as a magnetic resonance imaging (MRI) biomarker of tissue perfusion. We hypothesize that the superparamagnetic iron-oxide nanoparticle, ferumoxytol, sensitizes T1 to changes in the intramyocardial vascular compartment and improves the sensitivity and specificity of T1 reactivity as an imaging biomarker of tissue perfusion. We aim to assess the diagnostic performance of ferumoxytol-enhanced (FE) myocardial T1 reactivity in swine models of myocardial hypoperfusion. We induced acute myocardial hypoperfusion in 13 swine via percutaneous, transcatheter deployment of a 3D printed intracoronary stenosis implant into the left anterior descending coronary artery. We performed native and FE adenosine stress testing using 5(3)3(3)3 MOLLI and SASHA T1 mapping sequences with bSSFP readout on a clinical 3.0 T magnet. MOLLI T1 maps were fitted using both the conventional MOLLI and the Instantaneous Signal Loss (InSiL) T1-fitting algorithms. Regardless of the MOLLI or SASHA pulse sequence or T1-fitting algorithm, ferumoxytol contrast increased the dynamic range of T1 reactivity in both the remote and ischemic myocardial regions. Relative to remote myocardium, native and FE T1 reactivity were blunted in ischemic myocardium (p < 0.05) with InSiL-MOLLI, MOLLI and SASHA. An InSiL-MOLLI-derived FE T1 reactivity threshold of −4.65% had 73.3% sensitivity and 96.2% specificity for prediction of regional wall motion abnormalities (AUC 0.915, 95% CI 0.786-0.979), whereas a SASHA-derived FE T1 reactivity threshold of −5.25% had 75.0% sensitivity and 95.2% specificity (AUC 0.905, 95% CI 0.751-0.979). Ferumoxytol significantly increased the dynamic range of T1 reactivity as a measure of myocardial hypoperfusion in vasodilator stress T1 mapping studies. FE T1 reactivity maps can be used to quantitatively distinguish ischemic and remote myocardium with high specificity in swine models of acute myocardial hypoperfusion.

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Background The ultrasmall, superparamagnetic iron oxide (USPIO) nanoparticle ferumoxytol has unique applications in cardiac, vascular, and body magnetic resonance imaging (MRI) due to its long intravascular half‐life and suitability as a blood pool agent. However, limited availability and high cost have hindered its clinical adoption. A new ferumoxytol generic, and the emergence of MoldayION as an alternative USPIO, represent opportunities to expand the use of USPIO‐enhanced MRI techniques. Purpose To compare in vitro and in vivo MRI relaxometry and enhancement of Feraheme, generic ferumoxytol, and MoldayION. Study Type Prospective. Animal Model Ten healthy swine and six swine with artificially induced coronary narrowing underwent cardiac MRI. Field Strength/Sequence 3.0 T; T1‐weighted (4D‐MUSIC, 3D‐VIBE, 2D‐MOLLI) and T2‐weighted (2D‐HASTE) sequences pre‐ and post‐contrast. Assessment We compared the MRI relaxometry of Feraheme, generic ferumoxytol, and MoldayION using saline, plasma, and whole blood MRI phantoms with contrast concentrations from 0.26 mM to 2.10 mM. In‐vivo contrast effects on T1‐ and T2‐weighted sequences and fractional intravascular contrast distribution volume in myocardium, liver, and spleen were evaluated. Statistical Tests Analysis of variance and covariance were used for group comparisons. A P value <0.05 was considered statistically significant. Results The r1 relaxivities for Feraheme, generic ferumoxytol, and MoldayION in saline (22 °C) were 7.11 ± 0.13 mM−1 s−1, 8.30 ± 0.29 mM−1 s−1, 8.62 ± 0.16 mM−1 s−1, and the r2 relaxivities were 111.74 ± 3.76 mM−1 s−1, 105.07 ± 2.20 mM−1 s−1, and 109.68 ± 2.56 mM−1 s−1, respectively. The relationship between contrast concentration and longitudinal (R1) and transverse (R2) relaxation rate was highly linear in saline and plasma. The three agents produced similar in vivo contrast effects on T1 and T2 relaxation time‐weighted sequences. Data Conclusion Relative to clinically approved ferumoxytol formulations, MoldayION demonstrates minor differences in in vitro relaxometry and comparable in vivo MRI characteristics. Level of Evidence 2 Technical Efficacy Stage 1

This study evaluates the implementation of volumetric‐modulated arc therapy (VMAT) using multicriteria optimization (MCO) in the RayStation treatment planning system (TPS) for complex sites, namely extremity and body sarcoma. The VMAT‐MCO algorithm implemented in RayStation is newly developed and requires an integrated, comprehensive analysis of plan generation, delivery, and treatment efficiency. Ten patients previously treated by intensity‐modulated radiation therapy (IMRT) with MCO were randomly selected and replanned using VMAT‐MCO. The plan quality was compared using homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV) and dose sparing of organs at risk (OARs). Given the diversity of the tumor location, the 10 plans did not have a common OAR except for skin. The skin D50 and Ditalicmean was directly compared between VMAT‐MCO and IMRT‐MCO. Additional OAR dose points were compared on a plan‐by‐plan basis. The treatment efficiency was compared using plan monitor units (MU) and net beam‐on time. Plan quality assurance was performed using the Sun Nuclear ArcCHECK phantom and a gamma criteria of 3%/3 mm. No statistically significant differences were found between VMAT‐ and IMRT‐MCO for HI and CI of the PTV or D50 and Ditalicmean to the skin. The VMAT‐MCO plans showed general improvements in sparing to OARs. The VMAT‐MCO plan set showed statistically significant improvements over the IMRT‐MCO set in treatment efficiency per plan MU (p<0.05) and net beam‐on time (p<0.01). The VMAT‐MCO plan deliverability was validated. Similar gamma passing rates were observed for the two modalities. This study verifies the suitability of VMAT‐MCO for sarcoma cancer and highlighted the comparability in plan quality and improvement in treatment efficiency offered by VMAT‐MCO as compared to IMRT‐MCO.PACS number(s): separated by commas 87.55.D, 87.55.de, 87.55.Qr

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