Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

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.

Improved Robustness for Deep Learning-based Segmentation of Multi-Center Myocardial Perfusion MRI Datasets Using Data Adaptive Uncertainty-guided Space-time Analysis.

BACKGROUND: Fully automatic analysis of myocardial perfusion MRI datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge. METHODS: Datasets from 3 medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models against differences in pulse sequence (exD-1) and scanner vendor (exD-2). A subset of inD (n = 85) was used for training/validation of a pool of DNNs for segmentation, all using the same spatiotemporal U-Net architecture and hyperparameters but with different parameter initializations. We employed a space-time sliding-patch analysis approach that automatically yields a pixel-wise "uncertainty map" as a byproduct of the segmentation process. In our approach, dubbed Data Adaptive Uncertainty-Guided Space-time (DAUGS) analysis, a given test case is segmented by all members of the DNN pool and the resulting uncertainty maps are leveraged to automatically select the "best" one among the pool of solutions. For comparison, we also trained a DNN using the established approach with the same settings (hyperparameters, data augmentation, etc.). RESULTS: The proposed DAUGS analysis approach performed similarly to the established approach on the internal dataset (Dice score for the testing subset of inD: 0.896 ± 0.050 vs. 0.890 ± 0.049; p = n.s.) whereas it significantly outperformed on the external datasets (Dice for exD-1: 0.885 ± 0.040 vs. 0.849 ± 0.065, p < 0.005; Dice for exD-2: 0.811 ± 0.070 vs. 0.728 ± 0.149, p < 0.005). Moreover, the number of image series with "failed" segmentation (defined as having myocardial contours that include bloodpool or are noncontiguous in ≥1 segment) was significantly lower for the proposed vs. the established approach (4.3% vs. 17.1%, p < 0.0005). CONCLUSIONS: The proposed DAUGS analysis approach has the potential to improve the robustness of deep learning methods for segmentation of multi-center stress perfusion datasets with variations in the choice of pulse sequence, site location or scanner vendor.

Evaluation of coronary microvascular dysfunction and risk factors in children and youth with Turner syndrome by magnetic resonance myocardial perfusion imaging.

OBJECTIVE: Turner syndrome (TS) has an increased predisposition to ischaemic heart disease and the status of coronary microcirculation in TS is largely unknown. This study aims to evaluate myocardial microvascular function in TS using first-pass magnetic resonance perfusion imaging and determine significant risk factors contributing to microvascular dysfunction in the early stage. DESIGN: Perspective cohort study. PATIENTS: The study cohort consisted of 67 children and youth with TS and 32 age- and gender-matched controls. Measurements Clinical characteristics, left ventricle (LV) volume and function and cardiovascular magnetic resonance-derived myocardial perfusion parameters were assessed. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for microvascular dysfunction. RESULT: Microvascular perfusion decreased in TS in global and segmented myocardium as reflected in the lower upslopecor and maximum signal intensity (MaxSI) of LV myocardium compared to controls. Multivariable linear regression analysis indicated that age (ß = -0.107, 95% confidence interval [CI] = -0.201 to -0.013, p = .026) and being overweight/obese (ß = -1.155, CI = -2.134 to -0.176, p = .021) were independent impact factors of microvascular dysfunction. Subgroup analysis showed the upslopecor of older patients with TS decreased more significantly compared with that of normal controls. Upslopecor and MaxSI were lower in overweight/obese patients with TS than in patients with normal body mass index (BMI) and controls. CONCLUSION: Myocardial microvascular dysfunction can occur in children and youth patients with TS. Age and overweight/obesity were the independent risk factors of microvascular dysfunction, which imply the importance of lowering BMI for the prevention of coronary heart disease in young TS population.

Incremental effect of coronary obstruction on myocardial microvascular dysfunction in type 2 diabetes mellitus patients evaluated by first-pass perfusion CMR study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) frequently coexists with obstructive coronary artery disease (OCAD), which are at increased risk for cardiovascular morbidity and mortality. This study aimed to investigate the impact of coronary obstruction on myocardial microcirculation function in T2DM patients, and explore independent predictors of reduced coronary microvascular perfusion. METHODS: Cardiac magnetic resonance (CMR) scanning was performed on 297 T2DM patients {188 patients without OCAD [T2DM(OCAD -)] and 109 with [T2DM(OCAD +)]} and 89 control subjects. CMR-derived perfusion parameters, including upslope, max signal intensity (MaxSI), and time to maximum signal intensity (TTM) in global and segmental (basal, mid-ventricular, and apical slices) were measured and compared among observed groups. According to the median of Gensini score (64), T2DM(OCAD +) patients were subdivided into two groups. Univariable and multivariable linear regression analyses were performed to identify independent predictors of microcirculation dysfunction. RESULTS: T2DM(OCAD -) patients, when compared to control subjects, had reduced upslope and prolonged TTM in global and all of three slices (all P < 0.05). T2DM(OCAD +) patients showed a significantly more severe impairment of microvascular perfusion than T2DM(OCAD -) patients and control subjects with a more marked decline upslope and prolongation TTM in global and three slices (all P < 0.05). From control subjects, through T2DM(OCAD +) patients with Gensini score ≤ 64, to those patients with Gensini score > 64 group, the upslope declined and TTM prolonged progressively in global and mid-ventricular slice (all P < 0.05). The presence of OCAD was independently correlated with reduced global upslope (ß = - 0.104, P < 0.05) and global TTM (ß = 0.105, P < 0.05) in patients with T2DM. Among T2DM(OCAD +) patients, Gensini score was associated with prolonged global TTM (r = 0.34, P < 0.001). CONCLUSIONS: Coronary artery obstruction in the context of T2DM exacerbated myocardial microcirculation damage. The presence of OCAD and Gensini score were independent predictors of decreased microvascular function. TRIAL REGISTRATION: Retrospectively registered.

Myocardial First-Pass Perfusion With Increased Anatomic Coverage at 3 T Using Autocalibrated Multiband Imaging.

BACKGROUND: Myocardial first-pass perfusion (FPP) imaging is a useful cardiac MRI method for the diagnosis of coronary artery disease. However, conventional 2D multislice FPP acquisitions usually have gaps between myocardium slices, which limits the overall assessment of myocardial ischemia. PURPOSE: To increase the anatomic coverage of myocardial FPP imaging at 3 T by implementing both autocalibrated multiband (MB) acquisition and k-t space acceleration with compress sensing (CS) reconstruction, without the need for additional reference scans. STUDY TYPE: Phantom and prospective human studies. PHANTOM/SUBJECTS: A T1MES (T1 Mapping and ECV Standardization in cardiovascular magnetic resonance) phantom and 20 subjects (12 healthy subjects and 8 patients, 10 males, age 42 ± 16 years). FIELD STRENGTH/SEQUENCE: A 3 T/saturation recovery prepared gradient echo sequence with contrast administration. ASSESSMENT: Phantom experiments were performed to compare the performance of autocalibrated MB-FPP with k-t acceleration using slice-GRAPPA and CS reconstructions. In vivo experiments were performed to compare the performance of conventional FPP (2.5× acceleration) with autocalibrated MB + CS-FPP (6× acceleration). In phantom experiments, the error maps were calculated. In in vivo experiments, the contrast ratio (CR) and blurring were quantitatively measured, while image quality, perceived signal-to-noise ratio (SNR), and artifact level were qualitatively graded by three cardiologists on a 4-point scale. STATISTICAL TESTS: Wilcoxon signed-rank test, paired t-test. A P value <0.05 was considered statistically significant. RESULTS: In phantom experiments, residual artifact was reduced using the MB + CS-FPP reconstruction method compared with using the MB + slice-GRAPPA reconstruction method. In in vivo experiments, the proposed autocalibrated MB + CS-FPP method demonstrated significantly higher CR (3.52 ± 0.78 vs 2.91 ± 0.81) and had significantly better perceived SNR (2.69 ± 0.29 vs 2.48 ± 0.31) compared to the conventional sequence. Compared with conventional FPP, MB + CS-FPP doubled the spatial coverage (MB + CS-FPP vs conventional FPP) without compromising the image quality (2.69 ± 0.26 vs 2.60 ± 0.30) or increasing the artifact level (2.60 ± 0.26 vs 2.52 ± 0.31). CONCLUSION: Autocalibrated MB + CS-FPP improved the myocardial coverage and achieved comparable image quality with the same spatial resolution and scan time as conventional FPP and is a promising technique for clinical myocardial perfusion imaging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

DEep learning-based rapid Spiral Image REconstruction (DESIRE) for high-resolution spiral first-pass myocardial perfusion imaging.

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) technique for high-resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage, to provide fast and accurate image reconstruction for both single-slice (SS) and simultaneous multislice (SMS) acquisitions. Three-dimensional U-Net-based image enhancement architectures were evaluated for high-resolution spiral perfusion imaging at 3 T. The SS and SMS MB = 2 networks were trained on SS perfusion images from 156 slices from 20 subjects. Structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized root mean square error (NRMSE) were assessed, and prospective images were blindly graded by two experienced cardiologists (5: excellent; 1: poor). Excellent performance was demonstrated for the proposed technique. For SS, SSIM, PSNR, and NRMSE were 0.977 [0.972, 0.982], 42.113 [40.174, 43.493] dB, and 0.102 [0.080, 0.125], respectively, for the best network. For SMS MB = 2 retrospective data, SSIM, PSNR, and NRMSE were 0.961 [0.950, 0.969], 40.834 [39.619, 42.004] dB, and 0.107 [0.086, 0.133], respectively, for the best network. The image quality scores were 4.5 [4.1, 4.8], 4.5 [4.3, 4.6], 3.5 [3.3, 4], and 3.5 [3.3, 3.8] for SS DESIRE, SS L1-SPIRiT, MB = 2 DESIRE, and MB = 2 SMS-slice-L1-SPIRiT, respectively, showing no statistically significant difference (p = 1 and p = 1 for SS and SMS, respectively) between L1-SPIRiT and the proposed DESIRE technique. The network inference time was ~100 ms per dynamic perfusion series with DESIRE, while the reconstruction time of L1-SPIRiT with GPU acceleration was ~ 30 min. It was concluded that DESIRE enabled fast and high-quality image reconstruction for both SS and SMS MB = 2 whole-heart high-resolution spiral perfusion imaging.

High spatial resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage at 3 T.

PURPOSE: To develop and evaluate a high spatial resolution (1.25 × 1.25 mm2 ) spiral first-pass myocardial perfusion imaging technique with whole-heart coverage at 3T, to better assess transmural differences in perfusion between the endocardium and epicardium, to quantify the myocardial ischemic burden, and to improve the detection of obstructive coronary artery disease. METHODS: Whole-heart high-resolution spiral perfusion pulse sequences and corresponding motion-compensated reconstruction techniques for both interleaved single-slice (SS) and simultaneous multi-slice (SMS) acquisition with or without outer-volume suppression (OVS) were developed. The proposed techniques were evaluated in 34 healthy volunteers and 8 patients (55 data sets). SS and SMS images were reconstructed using motion-compensated L1-SPIRiT and SMS-Slice-L1-SPIRiT, respectively. Images were blindly graded by 2 experienced cardiologists on a 5-point scale (5, excellent; 1, poor). RESULTS: High-quality perfusion imaging was achieved for both SS and SMS acquisitions with or without OVS. The SS technique without OVS had the highest scores (4.5 [4, 5]), which were greater than scores for SS with OVS (3.5 [3.25, 3.75], P < .05), MB = 2 without OVS (3.75 [3.25, 4], P < .05), and MB = 2 with OVS (3.75 [2.75, 4], P < .05), but significantly higher than those for MB = 3 without OVS (4 [4, 4], P = .95). SMS image quality was improved using SMS-Slice-L1-SPIRiT as compared to SMS-L1-SPIRiT (P < .05 for both reviewers). CONCLUSION: We demonstrated the successful implementation of whole-heart spiral perfusion imaging with high resolution at 3T. Good image quality was achieved, and the SS without OVS showed the best image quality. Evaluation in patients with expected ischemic heart disease is warranted.

Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

The additive effects of obesity on myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance first-pass perfusion study.

BACKGROUND: The microvascular effects of obesity should be considered in diabetic individuals for elucidating underlying mechanisms and developing targeted therapies. This study aims to determine the effect of obesity on myocardial microvascular function in type 2 diabetes mellitus (T2DM) patients using cardiac magnetic resonance (CMR) first-pass perfusion imaging and assessed significant risk factors for microvascular dysfunction. MATERIALS AND METHODS: Between September 2016 and May 2018, 120 patients with T2DM (45.8% women [55 of 120]; mean age, 56.45 ± 11.97 years) and 79 controls (44.3% women [35 of 79]; mean age, 54.50 ± 7.79 years) with different body mass index (BMI) scales were prospectively enrolled and underwent CMR examination. CMR-derived perfusion parameters, including upslope, time to maximum signal intensity (TTM), maximum signal intensity (MaxSI), MaxSI (-baseline), and SI (baseline), and T2DM related risk factors were analyzed among groups/subgroups both in T2DM patients and controls. Univariable and multivariable linear and logistic regression analyses were performed to assess the potential additive effect of obesity on microvascular dysfunction in diabetic individuals. RESULTS: Compared with controls with comparable BMIs, patients with T2DM showed reduced upslope and MaxSI and increased TTM. For both T2DM and control subgroups, perfusion function gradually declined with increasing BMI, which was confirmed by all perfusion parameters, except for TTM (all P < 0.01). In multivariable linear regression analysis, BMI (ß = - 0.516; 95% confidence interval [CI], - 0.632 to - 0.357; P < 0.001), female sex (ß = 0.372; 95% CI, 0.215 to 0.475; P < 0.001), diabetes duration (ß = - 0.169; 95% CI, - 0.319 to - 0.025; P = 0.022) and glycated haemoglobin (ß = - 0.184; 95% CI, - 0.281 to - 0.039; P = 0.010) were significantly associated with global upslope in the T2DM group. Multivariable logistic regression analysis indicated that T2DM was an independent predictor of microvascular dysfunction in normal-weight (odds ratio[OR], 6.46; 95% CI, 2.08 to 20.10; P = 0.001), overweight (OR, 7.19; 95% CI, 1.67 to 31.07; P = 0.008) and obese participants (OR, 11.21; 95% CI, 2.38 to 52.75; P = 0.002). CONCLUSIONS: Myocardial microvascular function gradually declined with increasing BMI in both diabetes and non-diabetes status. T2DM was associated with an increased risk of microvascular dysfunction, and obesity exacerbated the adverse effect of T2DM.

Feasibility of real-time cardiac MRI in mice using tiny golden angle radial sparse.

Cardiovascular magnetic resonance imaging has proven valuable for the assessment of structural and functional cardiac abnormalities. Even although it is an established imaging method in small animals, the long acquisition times of gated or self-gated techniques still limit its widespread application. In this study, the application of tiny golden angle radial sparse MRI (tyGRASP) for real-time cardiac imaging was tested in 12 constitutive nexilin (Nexn) knock-out (KO) mice, both heterozygous (Het, N = 6) and wild-type (WT, N = 6), and the resulting functional parameters were compared with a well-established self-gating approach. Real-time images were reconstructed for different temporal resolutions of between 16.8 and 79.8 ms per image. The suggested approach was additionally tested for dobutamine stress and qualitative first-pass perfusion imaging. Measurements were repeated twice within 2 weeks for reproducibility assessment. In direct comparison with the high-quality, self-gated technique, the real-time approach did not show any significant differences in global function parameters for acquisition times below 50 ms (rest) and 31.5 ms (stress). Compared with WT, the end-diastolic volume (EDV) and end-systolic volume (ESV) were markedly higher (P < 0.05) and the ejection fraction (EF) was significantly lower in the Het Nexn-KO mice at rest (P < 0.001). For the stress investigation, a clear decrease of EDV and ESV, and an increase in EF, but maintained stroke volume, could be observed in both groups. Combined with ECG-triggering, tyGRASP provided first-pass perfusion data with a temporal resolution of one image per heartbeat, allowing the quantitative assessment of upslope curves in the blood-pool and myocardium. Excellent inter-study reproducibility was achieved in all the functional parameters. The tyGRASP is a valuable real-time MRI technique for mice, which significantly reduces the scan time in preclinical cardiac functional imaging, providing sufficient image quality for deriving accurate functional parameters, and has the potential to investigate real-time and beat-to-beat changes.

Whole-heart spiral simultaneous multi-slice first-pass myocardial perfusion imaging.

PURPOSE: To develop and evaluate a simultaneous multislice (SMS) spiral perfusion pulse sequence with whole-heart coverage. METHODS: An orthogonal set of phase cycling angles following a Hadamard pattern was incorporated into a golden-angle (GA) variable density spiral perfusion sequence to perform SMS imaging at different multiband (MB) factors. Images were reconstructed using an SMS extension of L1-SPIRiT that we have termed SMS-L1-SPIRiT. The proposed sequence was evaluated in 40 subjects (10 each for MB factors of 1, 2, 3, and 4). Images were blindly graded by 2 cardiologists on a 5-point scale (5, excellent). To quantitatively evaluate the reconstruction performance against images acquired without SMS, the MB =1 data were used to retrospectively simulate data acquired at MB factors of 2 to 4. RESULTS: Analysis of the SMS point-spread function for the desired slice showed that the proposed sampling strategy significantly canceled the main-lobe energy of the other slices and has low side-lobe energy resulting in an incoherent temporal aliasing pattern when rotated by the GA. Retrospective experiments demonstrated the SMS-L1-SPIRiT method removed aliasing from the interfering slices and showed excellent agreement with the ground-truth MB =1 images. Clinical evaluation demonstrated high-quality perfusion images with average image-quality scores of 4.3 ± 0.5 (MB =2), 4.2 ± 0.5 (MB =3), and 4.4 ± 0.4 (MB =4) with no significant quality difference in image quality between MB factors (P = 0.38). CONCLUSION: SMS spiral perfusion at MB factors 2, 3, and 4 produces high-quality perfusion images with whole-heart coverage in a clinical setting with high sampling efficiency.

Reduced field of view single-shot spiral perfusion imaging.

PURPOSE: To develop a single-shot spiral perfusion pulse sequence with outer-volume suppression (OVS) to achieve whole-heart coverage with a short temporal footprint of 10 ms per slice location. METHODS: A highly accelerated single-shot variable density spiral pulse sequence with an integrated OVS module for reduced field of view (rFOV) perfusion imaging with 2 mm spatial resolution was developed and evaluated in simulations, phantom experiments and in clinical patients with (n = 8) or without (n = 8) OVS. Images were reconstructed by block low-rank sparsity with motion guidance (BLOSM) and graded by two cardiologists on a 5-point scale (1, excellent; 5, poor). RESULTS: Simulation and phantom results showed that OVS effectively suppressed the signal outside the desired field of view (FOV). Clinical patient data demonstrated high quality perfusion images with rFOV. The average image quality scores of full FOV cases and rFOV cases were 3.1 ± 0.64 and 2.3 ± 0.46, respectively, (P = 0.02) from cardiologist 1 and 2.5 ± 0.54 and 1.8 ± 0.47, respectively, (P = 0.04) from cardiologist 2, showing superior image quality for the rFOV images compared with the full FOV images. CONCLUSION: A single-shot spiral perfusion sequence that uses OVS and BLOSM performs perfusion imaging with a very short temporal footprint per image supporting whole-heart coverage with good image quality. Magn Reson Med 79:208-216, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13 C]pyruvate and 13 C-urea.

PURPOSE: To demonstrate the feasibility of imaging a bolus of co-polarized [1-13 C]pyruvate and 13 C-urea to simultaneously assess both metabolism and perfusion in the rodent heart. METHODS: Copolarized [1-13 C]pyruvate and 13 C-urea was imaged using a multi-echo, flow-sensitized spiral pulse sequence. Healthy rats were scanned in a two-factor factorial design (n = 12 total; metabolism: overnight fasting versus fed with dichloroacetate injection; perfusion: rest versus adenosine stress-induced hyperemia). RESULTS: Alterations in metabolism were detected by changes in pyruvate metabolism into 13 C-bicarbonate. Statistically independent alterations in perfusion were detected by changes in myocardial pyruvate and urea signals. CONCLUSION: The new pulse sequence was used to obtain maps of metabolism and perfusion in the rodent heart in a single acquisition. This hyperpolarized 13 C imaging test is expected to enable new studies in which the cardiac metabolism/perfusion mismatch can be studied in the acute environment. Magn Reson Med 77:151-158, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

First-pass myocardial perfusion MRI with reduced subendocardial dark-rim artifact using optimized Cartesian sampling.

PURPOSE: The presence of subendocardial dark-rim artifact (DRA) remains an ongoing challenge in first-pass perfusion (FPP) cardiac magnetic resonance imaging (MRI). We propose a free-breathing FPP imaging scheme with Cartesian sampling that is optimized to minimize the DRA and readily enables near-instantaneous image reconstruction. MATERIALS AND METHODS: The proposed FPP method suppresses Gibbs ringing effects-a major underlying factor for the DRA-by "shaping" the underlying point spread function through a two-step process: 1) an undersampled Cartesian sampling scheme that widens the k-space coverage compared to the conventional scheme; and 2) a modified parallel-imaging scheme that incorporates optimized apodization (k-space data filtering) to suppress Gibbs-ringing effects. Healthy volunteer studies (n = 10) were performed to compare the proposed method against the conventional Cartesian technique-both using a saturation-recovery gradient-echo sequence at 3T. Furthermore, FPP imaging studies using the proposed method were performed in infarcted canines (n = 3), and in two symptomatic patients with suspected coronary microvascular dysfunction for assessment of myocardial hypoperfusion. RESULTS: Width of the DRA and the number of DRA-affected myocardial segments were significantly reduced in the proposed method compared to the conventional approach (width: 1.3 vs. 2.9 mm, P < 0.001; number of segments: 2.6 vs. 8.7; P < 0.0001). The number of slices with severe DRA was markedly lower for the proposed method (by 10-fold). The reader-assigned image quality scores were similar (P = 0.2), although the quantified myocardial signal-to-noise ratio was lower for the proposed method (P < 0.05). Animal studies showed that the proposed method can detect subendocardial perfusion defects and patient results were consistent with the gold-standard invasive test. CONCLUSION: The proposed free-breathing Cartesian FPP imaging method significantly reduces the prevalence of severe DRAs compared to the conventional approach while maintaining similar resolution and image quality. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:542-555.

Hyperpolarized 13C urea myocardial first-pass perfusion imaging using velocity-selective excitation.

BACKGROUND: A velocity-selective binomial excitation scheme for myocardial first-pass perfusion measurements with hyperpolarized 13C substrates, which preserves bolus magnetization inside the blood pool, is presented. The proposed method is evaluated against gadolinium-enhanced 1H measurements in-vivo. METHODS: The proposed excitation with an echo-planar imaging readout was implemented on a clinical CMR system. Dynamic myocardial stress perfusion images were acquired in six healthy pigs after bolus injection of hyperpolarized 13C urea with the velocity-selective vs. conventional excitation, as well as standard 1H gadolinium-enhanced images. Signal-to-noise, contrast-to-noise (CNR) and homogeneity of semi-quantitative perfusion measures were compared between methods based on first-pass signal-intensity time curves extracted from a mid-ventricular slice. Diagnostic feasibility is demonstrated in a case of septal infarction. RESULTS: Velocity-selective excitation provides over three-fold reduction in blood pool signal with a two-fold increase in myocardial CNR. Extracted first-pass perfusion curves reveal a significantly reduced variability of semi-quantitative first-pass perfusion measures (12-20%) for velocity-selective excitation compared to conventional excitation (28-93%), comparable to that of reference 1H gadolinium data (9-15%). Overall image quality appears comparable between the velocity-selective hyperpolarized and gadolinium-enhanced imaging. CONCLUSION: The feasibility of hyperpolarized 13C first-pass perfusion CMR has been demonstrated in swine. Comparison with reference 1H gadolinium data revealed sufficient data quality and indicates the potential of hyperpolarized perfusion imaging for human applications.

Assessment of myocardial ischemia by strain dobutamine stress echocardiography and cardiac magnetic resonance perfusion imaging before and after coronary artery bypass grafting.

BACKGROUND: Following coronary artery bypass grafting (CABG), testing for myocardial ischemia by noninvasive imaging is often hampered by false-positive results. The aim of this study was to find test parameters with the best potential to identify myocardial ischemia in post-CABG patients. METHODS: Fifty-two consecutive patients scheduled for CABG, underwent both dobutamine stress echocardiography (DSE) and cardiac magnetic resonance first-pass perfusion imaging (CMR-FPPI) with adenosine vasodilation, before and 8-10 months after the surgical revascularization. A pathologic biphasic stress response (PBR) expresses the presence of contractile reserve during low-dose dobutamine that decreases to hypo- or akinesia provoked by high-dose dobutamine. During DSE, potential PBR, segmental wall-motion score (WMS) as well as peak-systolic longitudinal strain (PLS) at peak-dose dobutamine were assessed. RESULTS: Post-CABG, there was still a relatively high prevalence of ischemia-positive segments evaluated by deformation imaging, but the number of such segments was significantly lower by PBR (20% and 22%) compared with peak-dose strain and WMS (62% and 77%, respectively; P<.05). The use of PBR instead of peak-dose WMS and strain could reduce the number of false-positive test results post-CABG. CONCLUSION: Among all imaging modalities tested, PBR by WMS and strain may be useful parameters for identifying patients with the need for new revascularization. We furthermore found that DSE may be interpreted as positive when revealing at least three ischemia-positive segments. The sensitivity of these test modalities for detecting coronary restenosis needs to be determined in further studies on a cohort of symptomatic post-CABG patients.

Cardiac perfusion imaging using hyperpolarized (13)C urea using flow sensitizing gradients.

PURPOSE: To demonstrate the feasibility of imaging the first passage of a bolus of hyperpolarized (13)C urea through the rodent heart using flow-sensitizing gradients to reduce signal from the blood pool. METHODS: A flow-sensitizing bipolar gradient was optimized to reduce the bright signal within the cardiac chambers, enabling improved contrast of the agent within the tissue capillary bed. The gradient was incorporated into a dynamic golden angle spiral (13)C imaging sequence. Healthy rats were scanned during rest (n = 3) and under adenosine stress-induced hyperemia (n = 3). RESULTS: A two-fold increase in myocardial perfusion relative to rest was detected during adenosine stress-induced hyperemia, consistent with a myocardial perfusion reserve of two in rodents. CONCLUSION: The new pulse sequence was used to obtain dynamic images of the first passage of hyperpolarized (13)C urea in the rodent heart, without contamination from bright signal within the neighboring cardiac lumen. This probe of myocardial perfusion is expected to enable new hyperpolarized (13)C studies in which the cardiac metabolism/perfusion mismatch can be identified. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

Breathing maneuvers as a coronary vasodilator for myocardial perfusion imaging.

PURPOSE: A combined breathing maneuver of hyperventilation, followed by a long voluntary breathhold leads to coronary vasodilation. We investigated the impact of breathing maneuvers on MR first-pass cardiac perfusion imaging and its potential clinical utility. MATERIALS AND METHODS: We studied 24 healthy volunteers (37 ± 12 years; 62.5% men) on a clinical 3 Tesla MRI system and performed first-pass perfusion MR at rest, during a short breathhold (S-HVBH) following 60 s of hyperventilation, and at the end of a long breathhold (L-HVBH) following the hyperventilation, performed in random order. A blinded reader analyzed signal intensity upslope, upslope index, and time between 20 and 80% of maximal signal. RESULTS: All volunteers tolerated the breathing maneuvers well and completed the study protocol. The upslope of the signal-intensity-over-time curve was increased during S-HVBH (1.86 ± 0.70 units/s, P < 0.05) and at the end of L-LVBH (1.77 ± 0.82 units/s), when compared with baseline results (1.34 ± 0.58 units/s). Corrected for the arterial input, the upslope was higher at the end of the L-HVBH (0.095 ± 0.019 units/s versus 0.077 ± 0.016 units/s at rest, P < 0.01) as was the myocardial perfusion reserve index (1.25 ± 0.22 versus 1.09 ± 0.17; P < 0.001). In a multiple regression model, only gender, rate-pressure product, and breathhold time were independently and significantly related to the upslope (R = 0.771; P < 0.001). CONCLUSION: In conclusion, a voluntary long breathhold after hyperventilation leads to an increase of the myocardial perfusion reserve index. This may impact findings from current practice of first-pass perfusion imaging. The clinical utility of breathing maneuvers as a vasodilatory stimulus for first-pass perfusion imaging may warrant further research. J. MAGN. RESON. IMAGING 2016;44:947-955.

All-systolic non-ECG-gated myocardial perfusion MRI: Feasibility of multi-slice continuous first-pass imaging.

PURPOSE: To develop and test the feasibility of a new method for non-ECG-gated first-pass perfusion (FPP) cardiac MR capable of imaging multiple short-axis slices at the same systolic cardiac phase. METHODS: A magnetization-driven pulse sequence was developed for non-ECG-gated FPP imaging without saturation-recovery preparation using continuous slice-interleaved radial sampling. The image reconstruction method, dubbed TRACE, used self-gating based on reconstruction of a real-time image-based navigator combined with reference-constrained compressed sensing. Data from ischemic animal studies (n = 5) was used in a simulation framework to evaluate temporal fidelity. Healthy subjects (n = 5) were studied using both the proposed approach and the conventional method to compare the myocardial contrast-to-noise ratio (CNR). Patients (n = 2) underwent adenosine stress studies using the proposed method. RESULTS: Temporal fidelity of the developed method was shown to be sufficient at high heart-rates. The healthy volunteers studies demonstrated normal perfusion and no dark-rim artifacts. Compared with the conventional scheme, myocardial CNR for the proposed method was slightly higher (8.6 ± 0.6 versus 8.0 ± 0.7). Patient studies showed stress-induced perfusion defects consistent with invasive angiography. CONCLUSION: The presented methods and results demonstrate feasibility of the proposed approach for high-resolution non-ECG-gated FPP imaging of 3 myocardial slices at the same systolic phase, and indicate its potential for achieving desirable image quality (high CNR and no dark-rim artifacts).