Diagnostic confidence with quantitative cardiovascular magnetic resonance perfusion mapping increases with increased coverage of the left ventricle.

BACKGROUND: Quantitative cardiovascular magnetic resonance (CMR) first pass perfusion maps are conventionally acquired with 3 short-axis (SAX) views (basal, mid, and apical) in every heartbeat (3SAX/1RR). Thus, a significant part of the left ventricle (LV) myocardium, including the apex, is not covered. The aims of this study were 1) to investigate if perfusion maps acquired with 3 short-axis views sampled every other RR-interval (2RR) yield comparable quantitative measures of myocardial perfusion (MP) as 1RR and 2) to assess if acquiring 3 additional perfusion views (i.e., total of 6) every other RR-interval (2RR) increases diagnostic confidence. METHODS: In 287 patients with suspected ischemic heart disease stress and rest MP were performed on clinical indication on a 1.5T MR scanner. Eighty-three patients were examined by acquiring 3 short-axis perfusion maps with 1RR sampling (3SAX/1RR); for which also 2RR maps were reconstructed. Additionally, in 103 patients 3 short-axis and 3 long-axis (LAX; 2-, 3, and 4-chamber view) perfusion maps were acquired using 2RR sampling (3SAX + 3LAX/2RR) and in 101 patients 6 short-axis perfusion maps using 2RR sampling (6SAX/2RR) were acquired. The diagnostic confidence for ruling in or out stress-induced ischemia was scored according to a Likert scale (certain ischemia [2 points], probably ischemia [1 point], uncertain [0 points], probably no ischemia [1 point], certain no ischemia [2 points]). RESULTS: There was a strong correlation (R = 0.99) between 3SAX/1RR and 3SAX/2RR for global MP (mL/min/g). The diagnostic confidence score increased significantly when the number of perfusion views was increased from 3 to 6 (1.24 ± 0.68 vs 1.54 ± 0.64, p < 0.001 with similar increase for 3SAX+3LAX/2RR (1.29 ± 0.68 vs 1.55 ± 0.65, p < 0.001) and for 6SAX/2RR (1.19 ± 0.69 vs 1.53 ± 0.63, p < 0.001). CONCLUSION: Quantitative perfusion mapping with 2RR sampling of data yields comparable perfusion values as 1RR sampling, allowing for the acquisition of additional views within the same perfusion scan. The diagnostic confidence for stress-induced ischemia increases when adding 3 additional views, short- or long axes, to the conventional 3 short-axis views. Thus, future development and clinical implementation of quantitative CMR perfusion should aim at increasing the LV coverage from the current standard using 3 short-axis views.

Fetal 3D cardiovascular cine image acquisition using radial sampling and compressed sensing.

PURPOSE: To explore a fetal 3D cardiovascular cine acquisition using a radial image acquisition and compressed-sensing reconstruction and compare image quality and scan time with conventional multislice 2D imaging. METHODS: Volumetric fetal cardiac data were acquired in 26 volunteers using a radial 3D balanced SSFP pulse sequence. Cardiac gating was performed using a Doppler ultrasound device. Images were reconstructed using a parallel-imaging and compressed-sensing algorithm. Multiplanar reformatting to standard cardiac views was performed before image analysis. Clinical 2D images were used for comparison. Qualitative and quantitative image evaluation were performed by two experienced observers (scale: 1-4). Volumes, mass, and function were assessed. RESULTS: Average scan time for the 3D imaging was 6 min, including one localizer. A 2D imaging stack covering the entire heart including localizer sequences took at least 6.5 min, depending on planning complexity. The 3D acquisition was successful in 7 of 26 subjects (27%). Overall image contrast and perceived resolution were lower in the 3D images. Nonetheless, the 3D images had, on average, a moderate cardiac diagnostic quality (median [range]: 3 [1-4]). Standard clinical 2D acquisitions had a high cardiac diagnostic quality (median [range]: 4 [3, 4]). Cardiac measurements were not different between 2D and 3D images (all p > 0.16). CONCLUSION: The presented free-breathing whole-heart fetal 3D radial cine MRI acquisition and reconstruction method enables retrospective visualization of all cardiac views while keeping examination times short. This proof-of-concept work produced images with diagnostic quality, while at the same time reducing the planning complexity to a single localizer.

Factors affecting performance of fetal blood T2 measurements for noninvasive estimation of oxygen saturation.

PURPOSE: To ultimately make accurate and precise fetal noninvasive oxygen saturation (sO2 ) measurements by T2 -prepared bSSFP more widely available by systematically assessing error sources in order to potentially reduce perinatal mortality in cardiovascular malformations and fetal growth restriction. METHODS: T2 -prepared bSSFP data were acquired in phantoms; in flowing blood in adults in the superior sagittal sinus, ascending and descending aorta, and main pulmonary artery; and in the fetal descending aorta and umbilical vein. T2 was assessed in relation to T2 two- or three-parameter curve-fitting techniques, SSFP readout, refocusing time delay (τ), constant and pulsatile blood flow, and impact of T1 recovery. Further, fetal T2 and sO2 variability were quantified in the descending aorta and umbilical vein in healthy fetuses and fetuses with cardiovascular malformation (gestational weeks 32-38). RESULTS: In phantoms, three-parameter fitting was accurate irrespective of phase FOV (<4 ms; i.e., <2%), and T2 was overestimated (up to 23 ms/10%; p = 0.001) beyond ±30 Hz off-resonance. In the adult aorta, T2 was underestimated during higher blood flow velocities and pulsatility for τ = 16 ms (-41 ms/-17%; p = 0.008). In fetuses, two-parameter fitting overestimated T2 compared with three-parameter fitting (+33 ms/+18%; p = 0.03). T2 variability was 18 ms/15% in the fetal descending aorta and 28 ms/14% in the umbilical vein. The resulting estimated sO2 variability was ∼10% (15% of sO2 value) in the fetal descending aorta. CONCLUSIONS: Errors due to T2 -fitting techniques, off-resonance, flow velocity, and insufficient T1 recovery between image acquisitions could be mitigated by using three-parameter fitting with included saturation-prepared images approximating infinite T2 -preparation time, adequate shimming covering the fetus and placenta, and by modifying acquisition parameters. Variability in fetal blood T2 and sO2 , however, indicate that it is currently not feasible to use these methods for prediction of disease.

Super-Resolution Cine Image Enhancement for Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images. PURPOSE: To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks]). FIELD STRENGTH/SEQUENCE: 1.5 T, balanced steady-state free precession (bSSFP) cine sequence. ASSESSMENT: Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10. STATISTICAL TESTS: Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P < 0.05 showing statistically significant differences. RESULTS: Both proposed methods showed no significant difference in image quality compared to clinical images (8 [7-8.5]) down to 33% (phasrGAN 8 [6.5-8]; phasrresnet 8 [7-8], all P ≥ 0.19) phase-encoding resolution, i.e., up to three times faster image acquisition, whereas bicubic interpolation and k-space zeropadding showed significantly lower quality for 33% phase-encoding resolution (both 7 [6-8]). DATA CONCLUSION: Super-resolution enhancement can be used for fetal cine cardiac MRI to reduce image acquisition time while maintaining image quality. This may lead to an improved success rate for fetal cine MR imaging, as the impact of fetal motion is lessened by shortened acquisitions. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Infarct quantification with cardiovascular magnetic resonance using "standard deviation from remote" is unreliable: validation in multi-centre multi-vendor data.

BACKGROUND: The objective of the study was to investigate variability and agreement of the commonly used image processing method "n-SD from remote" and in particular for quantifying myocardial infarction by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). LGE-CMR in tandem with the analysis method "n-SD from remote" represents the current reference standard for infarct quantification. This analytic method utilizes regions of interest (ROIs) and defines infarct as the tissue with a set number of standard deviations (SD) above the signal intensity of remote nulled myocardium. There is no consensus on what the set number of SD is supposed to be. Little is known about how size and location of ROIs and underlying signal properties in the LGE images affect results. Furthermore, the method is frequently used elsewhere in medical imaging often without careful validation. Therefore, the usage of the "n-SD" method warrants a thorough validation. METHODS: Data from 214 patients from two multi-center cardioprotection trials were included. Infarct size from different remote ROI positions, ROI size, and number of standard deviations ("n-SD") were compared with reference core lab delineations. RESULTS: Variability in infarct size caused by varying ROI position, ROI size, and "n-SD" was 47%, 48%, and 40%, respectively. The agreement between the "n-SD from remote" method and the reference infarct size by core lab delineations was low. Optimal "n-SD" threshold computed on a slice-by-slice basis showed high variability, n = 5.3 ± 2.2. CONCLUSION: The "n-SD from remote" method is unreliable for infarct quantification due to high variability which depends on different placement and size of remote ROI, number "n-SD", and image signal properties related to the CMR-scanner and sequence used. Therefore, the "n-SD from remote" method should not be used, instead methods validated against an independent standard are recommended.

Measuring extracellular volume fraction by MRI: First verification of values given by clinical sequences.

PURPOSE: To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1-mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers. METHODS: Between May 2016 and March 2017, 8 volunteers (25 ± 4 years, 3 female) and 8 pigs (4 female) underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method. RESULTS: In pigs, ECV in normal myocardium was not different between radioisotope (average ± standard deviation; 19 ± 2%) and SASHA (21 ± 2%; P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope (P ≤ 0.001 for all). ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA (22 ± 3%; P = 0.022 and P = 0.033). No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs (0.08% and 0.07%/min; P = 0.004 and P = 0.013) and by MOLLI5s(3s)3s for volunteers (0.07%/min; P = 0.032) but did not increase as measured by SASHA. CONCLUSION: Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI-sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence.

Free-breathing fetal cardiac MRI with doppler ultrasound gating, compressed sensing, and motion compensation.

BACKGROUND: Fetal cardiovascular MRI complements ultrasound to assess fetal cardiovascular pathophysiology. PURPOSE: To develop a free-breathing method for retrospective fetal cine MRI using Doppler ultrasound (DUS) cardiac gating and tiny golden angle radial sampling (tyGRASP) for accelerated acquisition capable of detecting fetal movements for motion compensation. STUDY TYPE: Feasibility study. SUBJECTS: Nine volunteers (gestational week 34-40). Short-axis and four-chamber views were acquired during maternal free-breathing and breath-hold. FIELD STRENGTH/SEQUENCE: 1.5T cine balanced steady-state free precession. ASSESSMENT: A self-gated reconstruction method was improved for clinical application by using 1) retrospective DUS gating, and 2) motion detection and rejection/correction algorithms for compensating for fetal motion. The free-breathing reconstructions were qualitatively and quantitatively assessed, and DUS-gating was compared with self-gating in breath-hold reconstructions. A scoring of 1-4 for overall image quality, cardiac, and extracardiac diagnostic quality was used. STATISTICAL TESTS: Friedman's test was used to assess differences in qualitative scoring between observers. A Wilcoxon matched-pairs signed rank test was used to assess differences between breath-hold and free-breathing acquisitions and between observers' quantitative measurements. RESULTS: In all cases, 111 free-breathing and 145 breath-hold acquisitions, the automatically calculated DUS-based cardiac gating signal provided reconstructions of diagnostic quality (median score 4, range 1-4). Free-breathing did not affect the DUS-based cardiac gated retrospective radial reconstruction with respect to image or diagnostic quality (all P > 0.06). Motion detection with rejection/correction in k-space produced high-quality free-breathing DUS-based reconstructions [median 3, range (2-4)], whereas free-breathing self-gated methods failed in 80 out of 88 cases to produce a stable gating signal. DATA CONCLUSION: Free-breathing fetal cine cardiac MRI based on DUS gating and tyGRASP with motion compensation yields diagnostic images. This simplifies acquisition for the pregnant woman and thus could help increase fetal cardiac MRI acceptance in the clinic. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:260-272.

Independent validation of metric optimized gating for fetal cardiovascular phase-contrast flow imaging.

PURPOSE: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site. METHODS: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein. RESULTS: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein. CONCLUSION: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values.

Quantification of blood flow in the fetus with cardiovascular magnetic resonance imaging using Doppler ultrasound gating: validation against metric optimized gating.

INTRODUCTION: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. AIMS: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. METHODS: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265-400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. RESULTS: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. CONCLUSIONS: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

Importance of standardizing timing of hematocrit measurement when using cardiovascular magnetic resonance to calculate myocardial extracellular volume (ECV) based on pre- and post-contrast T1 mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can be used to calculate myocardial extracellular volume fraction (ECV) by relating the longitudinal relaxation rate in blood and myocardium before and after contrast-injection to hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which could affect the calculations of ECV. The aim of this study was to test the hypothesis that there is a significant increase in calculated ECV values if the Hct is sampled after the CMR examination in supine position compared to when the patient arrives at the MR department. METHODS: Forty-three consecutive patients including various pathologies as well as normal findings were included in the study. Venous blood samples were drawn upon arrival to the MR department and directly after the examination with the patient remaining in supine position. A Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid-ventricular short-axis images before and after contrast injection from which motion-corrected T1 maps were derived and ECV was calculated. RESULTS: Hematocrit decreased from 44.0 ± 3.7% before to 40.6 ± 4.0% after the CMR examination (p < 0.001). This resulted in a change in calculated ECV from 24.7 ± 3.8% before to 26.2 ± 4.2% after the CMR examination (p < 0.001). All patients decreased in Hct after the CMR examination compared to before except for two patients whose Hct remained the same. CONCLUSION: Variability in CMR-derived myocardial ECV can be reduced by standardizing the timing of Hct measurement relative to the CMR examination. Thus, a standardized acquisition of blood sample for Hct after the CMR examination, when the patient is still in supine position, would increase the precision of ECV measurements.

Dynamic fetal cardiovascular magnetic resonance imaging using Doppler ultrasound gating.

BACKGROUND: Fetal cardiovascular magnetic resonance (CMR) imaging may provide a valuable adjunct to fetal echocardiography in the evaluation of congenital cardiovascular pathologies. However, dynamic fetal CMR is difficult due to the lack of direct in-utero cardiac gating. The aim of this study was to investigate the effectiveness of a newly developed Doppler ultrasound (DUS) device in humans for fetal CMR gating. METHODS: Fifteen fetuses (gestational age 30-39 weeks) were examined using 1.5 T CMR scanners at three different imaging sites. A newly developed CMR-compatible DUS device was used to generate gating signals from fetal cardiac motion. Gated dynamic balanced steady-state free precession images were acquired in 4-chamber and short-axis cardiac views. Gating signals during data acquisition were analyzed with respect to trigger variability and sensitivity. Image quality was assessed by measuring endocardial blurring (EB) and by image evaluation using a 4-point scale. Left ventricular (LV) volumetry was performed using the single-plane ellipsoid model. RESULTS: Gating signals from the fetal heart were detected with a variability of 26 ± 22 ms and a sensitivity of trigger detection of 96 ± 4%. EB was 2.9 ± 0.6 pixels (4-chamber) and 2.5 ± 0.1 pixels (short axis). Image quality scores were 3.6 ± 0.6 (overall), 3.4 ± 0.7 (mitral valve), 3.4 ± 0.7 (foramen ovale), 3.6 ± 0.7 (atrial septum), 3.7 ± 0.5 (papillary muscles), 3.8 ± 0.4 (differentiation myocardium/lumen), 3.7 ± 0.5 (differentiation myocardium/lung), and 3.9 ± 0.4 (systolic myocardial thickening). Inter-observer agreement for the scores was moderate to very good (kappa 0.57-0.84) for all structures. LV volumetry revealed mean values of 2.8 ± 1.2 ml (end-diastolic volume), 0.9 ± 0.4 ml (end systolic volume), 1.9 ± 0.8 ml (stroke volume), and 69.1 ± 8.4% (ejection fraction). CONCLUSION: High-quality dynamic fetal CMR was successfully performed using a newly developed DUS device for direct fetal cardiac gating. This technique has the potential to improve the utility of fetal CMR in the evaluation of congenital pathologies.

Self-gated fetal cardiac MRI with tiny golden angle iGRASP: A feasibility study.

PURPOSE: To develop and assess a technique for self-gated fetal cardiac cine magnetic resonance imaging (MRI) using tiny golden angle radial sampling combined with iGRASP (iterative Golden-angle RAdial Sparse Parallel) for accelerated acquisition based on parallel imaging and compressed sensing. MATERIALS AND METHODS: Fetal cardiac data were acquired from five volunteers in gestational week 29-37 at 1.5T using tiny golden angles for eddy currents reduction. The acquired multicoil radial projections were input to a principal component analysis-based compression stage. The cardiac self-gating (CSG) signal for cardiac gating was extracted from the acquired radial projections and the iGRASP reconstruction procedure was applied. In all acquisitions, a total of 4000 radial spokes were acquired within a breath-hold of less than 15 seconds using a balanced steady-state free precession pulse sequence. The images were qualitatively compared by two independent observers (on a scale of 1-4) to a single midventricular cine image from metric optimized gating (MOG) and real-time acquisitions. RESULTS: For iGRASP and MOG images, good overall image quality (2.8 ± 0.4 and 2.6 ± 1.3, respectively, for observer 1; 3.6 ± 0.5 and 3.4 ± 0.9, respectively, for observer 2) and cardiac diagnostic quality (3.8 ± 0.4 and 3.4 ± 0.9, respectively, for observer 1; 3.6 ± 0.5 and 3.6 ± 0.9, respectively, for observer 2) were obtained, with visualized myocardial thickening over the cardiac cycle and well-defined myocardial borders to ventricular lumen and liver/lung tissue. For iGRASP, MOG, and real time, left ventricular lumen diameter (14.1 ± 2.2 mm, 14.2 ± 1.9 mm, 14.7 ± 1.1 mm, respectively) and wall thickness (2.7 ± 0.3 mm, 2.6 ± 0.3 mm, 3.0 ± 0.4, respectively) showed agreement and no statistically significant difference was found (all P > 0.05). Images with iGRASP tended to have higher overall image quality scores compared with MOG and particularly real-time images, albeit not statistically significant in this feasibility study (P > 0.99 and P = 0.12, respectively). CONCLUSION: Fetal cardiac cine MRI can be performed with iGRASP using tiny golden angles and CSG. Comparison with other fetal cardiac cine MRI methods showed that the proposed method produces high-quality fetal cardiac reconstructions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:207-217.

Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

BACKGROUND: Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. METHODS: Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). RESULTS: There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2 = 0.92, p < 0.001), between ex-vivo and in-vivo CMR (bias 0 ± 2% LVM, r 2 = 0.94, p < 0.001) and between in-vivo CMR and MPS (bias -2 ± 3% LVM, r 2 = 0.87, p < 0.001. No change in MaR was seen over the first 30 min after contrast injection (p = 0.95). CONCLUSIONS: Contrast-enhanced SSFP cine CMR can be used to measure MaR, both in vivo and ex vivo, in a porcine model with good accuracy and precision over the first 30 min after contrast injection. This offers the option to use the less complex ex-vivo imaging when determining myocardial salvage in experimental studies.

Fully quantitative cardiovascular magnetic resonance myocardial perfusion ready for clinical use: a comparison between cardiovascular magnetic resonance imaging and positron emission tomography.

BACKGROUND: Recent studies have shown that quantification of myocardial perfusion (MP) at stress and myocardial perfusion reserve (MPR) offer additional diagnostic and prognostic information compared to qualitative and semi-quantitative assessment of myocardial perfusion distribution in patients with coronary artery disease (CAD). Technical advancements have enabled fully automatic quantification of MP using cardiovascular magnetic resonance (CMR) to be performed in-line in a clinical workflow. The aim of this study was to validate the use of the automated CMR perfusion mapping technique for quantification of MP using 13N-NH3 cardiac positron emission tomography (PET) as the reference method. METHODS: Twenty-one patients with stable CAD were included in the study. All patients underwent adenosine stress and rest perfusion imaging with 13N-NH3 PET and a dual sequence, single contrast bolus CMR on the same day. Global and regional MP were quantified both at stress and rest using PET and CMR. RESULTS: There was good agreement between global MP quantified by PET and CMR both at stress (-0.1 ± 0.5 ml/min/g) and at rest (0 ± 0.2 ml/min/g) with a strong correlation (r = 0.92, p < 0.001; y = 0.94× + 0.14). Furthermore, there was strong correlation between CMR and PET with regards to regional MP (r = 0.83, p < 0.001; y = 0.87× + 0.26) with a good agreement (-0.1 ± 0.6 ml/min/g). There was also a significant correlation between CMR and PET with regard to global and regional MPR (r = 0.69, p = 0.001 and r = 0.57, p < 0.001, respectively). CONCLUSIONS: There is good agreement between MP quantified by 13N-NH3 PET and dual sequence, single contrast bolus CMR in patients with stable CAD. Thus, CMR is viable in clinical practice for quantification of MP.

Validation of a new T2* algorithm and its uncertainty value for cardiac and liver iron load determination from MRI magnitude images.

PURPOSE: To validate an automatic algorithm for offline T2* measurements, providing robust, vendor-independent T2*, and uncertainty estimates for iron load quantification in the heart and liver using clinically available imaging sequences. METHODS: A T2* region of interest (ROI)-based algorithm was developed for robustness in an offline setting. Phantom imaging was performed on a 1.5 Tesla system, with clinically available multiecho gradient-recalled-echo (GRE) sequences for cardiac and liver imaging. A T2* single-echo GRE sequence was used as reference. Simulations were performed to assess accuracy and precision from 2000 measurements. Inter- and intraobserver variability was obtained in a patient study (n = 23). RESULTS: Simulations: Accuracy, in terms of the mean differences between the proposed method and true T2* ranged from 0-0.73 ms. Precision, in terms of confidence intervals of repeated measurements, was 0.06-4.74 ms showing agreement between the proposed uncertainty estimate and simulations. Phantom study: Bias and variability were 0.26 ± 4.23 ms (cardiac sequence) and -0.23 ± 1.69 ms (liver sequence). Patient study: Intraobserver variability was similar for experienced and inexperienced observers (0.03 ± 1.44 ms versus 0.16 ± 2.33 ms). Interobserver variability was 1.0 ± 3.77 ms for the heart and -0.52 ± 2.75 ms for the liver. CONCLUSION: The proposed algorithm was shown to provide robust T2* measurements and uncertainty estimates over the range of clinically relevant T2* values. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. METHODS: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). RESULTS: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). CONCLUSIONS: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CLINICAL TRIAL REGISTRATION: CHILL-MI: NCT01379261 . MITOCARE: NCT01374321 .

Validation of T1 and T2 algorithms for quantitative MRI: performance by a vendor-independent software.

BACKGROUND: Determination of the relaxation time constants T1 and T2 with quantitative magnetic resonance imaging is increasingly used for both research and clinical practice. Recently, groups have been formed within the Society of Cardiovascular Magnetic Resonance to address issues with relaxometry. However, so far they have avoided specific recommendations on methodology due to lack of consensus and current evolving research. Standardised widely available software may simplify this process. The purpose of the current study was to develop and validate vendor-independent T1 and T2 mapping modules and implement those in the versatile and widespread software Segment, freely available for research and FDA approved for clinical applications. RESULTS: The T1 and T2 mapping modules were developed and validated in phantoms at 1.5 T and 3 T with reference standard values calculated from reference pulse sequences using the Nelder-Mead Simplex optimisation method. The proposed modules support current commonly available MRI pulse sequences and both 2- and 3-parameter curve fitting. Images acquired in patients using three major vendors showed vendor-independence. Bias and variability showed high agreement with T1 and T2 reference standards for T1 (range 214-1752 ms) and T2 (range 45-338 ms), respectively. CONCLUSIONS: The developed and validated T1 and T2 mapping and quantification modules generated relaxation maps from current commonly used MRI sequences and multiple signal models. Patient applications showed usability for three major vendors.

Automatic segmentation of myocardium at risk from contrast enhanced SSFP CMR: validation against expert readers and SPECT.

BACKGROUND: Efficacy of reperfusion therapy can be assessed as myocardial salvage index (MSI) by determining the size of myocardium at risk (MaR) and myocardial infarction (MI), (MSI = 1-MI/MaR). Cardiovascular magnetic resonance (CMR) can be used to assess MI by late gadolinium enhancement (LGE) and MaR by either T2-weighted imaging or contrast enhanced SSFP (CE-SSFP). Automatic segmentation algorithms have been developed and validated for MI by LGE as well as for MaR by T2-weighted imaging. There are, however, no algorithms available for CE-SSFP. Therefore, the aim of this study was to develop and validate automatic segmentation of MaR in CE-SSFP. METHODS: The automatic algorithm applies surface coil intensity correction and classifies myocardial intensities by Expectation Maximization to define a MaR region based on a priori regional criteria, and infarct region from LGE. Automatic segmentation was validated against manual delineation by expert readers in 183 patients with reperfused acute MI from two multi-center randomized clinical trials (RCT) (CHILL-MI and MITOCARE) and against myocardial perfusion SPECT in an additional set (n = 16). Endocardial and epicardial borders were manually delineated at end-diastole and end-systole. Manual delineation of MaR was used as reference and inter-observer variability was assessed for both manual delineation and automatic segmentation of MaR in a subset of patients (n = 15). MaR was expressed as percent of left ventricular mass (%LVM) and analyzed by bias (mean ± standard deviation). Regional agreement was analyzed by Dice Similarity Coefficient (DSC) (mean ± standard deviation). RESULTS: MaR assessed by manual and automatic segmentation were 36 ± 10% and 37 ± 11%LVM respectively with bias 1 ± 6%LVM and regional agreement DSC 0.85 ± 0.08 (n = 183). MaR assessed by SPECT and CE-SSFP automatic segmentation were 27 ± 10%LVM and 29 ± 7%LVM respectively with bias 2 ± 7%LVM. Inter-observer variability was 0 ± 3%LVM for manual delineation and -1 ± 2%LVM for automatic segmentation. CONCLUSIONS: Automatic segmentation of MaR in CE-SSFP was validated against manual delineation in multi-center, multi-vendor studies with low bias and high regional agreement. Bias and variability was similar to inter-observer variability of manual delineation and inter-observer variability was decreased by automatic segmentation. Thus, the proposed automatic segmentation can be used to reduce subjectivity in quantification of MaR in RCT. CLINICAL TRIAL REGISTRATION: NCT01379261. NCT01374321.

Parallel simulations for QUAntifying RElaxation magnetic resonance constants (SQUAREMR): an example towards accurate MOLLI T1 measurements.

BACKGROUND: T1 mapping is widely used today in CMR, however, it underestimates true T1 values and its measurement error is influenced by several acquisition parameters. The purpose of this study was the extraction of accurate T1 data through the utilization of comprehensive, parallel Simulations for QUAntifying RElaxation Magnetic Resonance constants (SQUAREMR) of the MOLLI pulse sequence on a large population of spins with physiologically relevant tissue relaxation constants. METHODS: A CMR protocol consisting of different MOLLI schemes was performed on phantoms and healthy human volunteers. For every MOLLI experiment, the identical pulse sequence was simulated for a large range of physiological combinations of relaxation constants, resulting in a database of all possible outcomes. The unknown relaxation constants were then determined by finding the simulated signals in the database that produced the least squared difference to the measured signal intensities. RESULTS: SQUAREMR demonstrated improvement of accuracy in phantom studies and consistent mean T1 values and consistent variance across the different MOLLI schemes in humans. This was true even for tissues with long T1s and MOLLI schemes with no pause between modified-Look-Locker experiments. CONCLUSIONS: SQUAREMR enables quantification of T1 data obtained by existing clinical pulse sequences. SQUAREMR allows for correction of quantitative CMR data that have already been acquired whereas it is expected that SQUAREMR may improve data consistency and advance quantitative MR across imaging centers, vendors and experimental configurations. While this study is focused on a MOLLI-based T1-mapping technique, it could however be extended in other types of quantitative MRI throughout the body.