Quantification of balanced SSFP myocardial perfusion imaging at 1.5 T: Impact of the reference image.

PURPOSE: To investigate the use of a high flip-angle (HFA) balanced SSFP (bSSFP) reference image (in comparison to conventional proton density [PD]-weighted reference images) for conversion of bSSFP myocardial perfusion images into dynamic T1 maps for improved myocardial blood flow (MBF) quantification at 1.5 T. METHODS: The HFA-bSSFP (flip angle [FA] = 50°), PD gradient-echo (PD-GRE; FA = 5°), and PD-bSSFP (FA = 8°) reference images were acquired before a dual-sequence bSSFP perfusion acquisition. Simulations were used to study accuracy and precision of T1 and MBF quantification using the three techniques. The accuracy and precision of T1 , and the precision and intersegment variability of MBF were compared among the three techniques in 8 patients under rest conditions. RESULTS: In simulations, HFA-bSSFP demonstrated improved T1 /MBF precision (higher T1 /MBF SD of 30%-80%/50%-100% and 30%-90%/60%-115% for PD-GRE and PD-bSSFP, respectively). Proton density-GRE and PD-bSSFP were more sensitive to effective FA than HFA-bSSFP (maximum T1 /MBF errors of 13%/43%, 20%/43%, and 1%/3%, respectively). Sensitivity of all techniques (defined as T1 /MBF errors) to native T1 , native T2 , and effective saturation efficiency were negligible (<1%/<1%), moderate (<14%/<19%), and high (<63%/<94%), respectively. In vivo, no difference in T1 accuracy was observed among HFA-bSSFP, PD-GRE, and PD-bSSFP (-9 ± 44 ms vs -28 ± 55 ms vs -22 ± 71 ms, respectively; p > .08). The HFA-bSSFP led to improved T1 /MBF precision (T1 /MBF SD: 41 ± 19 ms/0.24 ± 0.08 mL/g/min vs PD-GRE: 48 ± 20 ms/0.29 ± 0.09 mL/g/min and PD-bSSFP: 59 ± 23 ms/0.33 ± 0.11 mL/g/min; p ≤ .02) and lower MBF intersegment variability (0.14 ± 0.09 mL/g/min vs PD-GRE: 0.21 ± 0.09 mL/g/min and PD-bSSFP: 0.20 ± 0.10 mL/g/min; p ≤ .046). CONCLUSION: We have demonstrated the feasibility of using a HFA-bSSFP reference image for MBF quantification of bSSFP perfusion imaging at 1.5 T. Results from simulations demonstrate that the HFA-bSSFP reference image results in improved precision and reduced sensitivity to effective FA compared with conventional techniques using a PD reference image. Preliminary in vivo data acquired at rest also demonstrate improved precision and intersegment variability using the HFA-bSSFP technique compared with PD techniques; however, a clinical study in patients with coronary artery disease under stress conditions is required to determine the clinical significance of this finding.

Impact of Temporal Resolution and Methods for Correction on Cardiac Magnetic Resonance Perfusion Quantification.

BACKGROUND: Acquisition of magnetic resonance first-pass perfusion images is synchronized to the patient's heart rate (HR) and governs the temporal resolution. This is inherently linked to the process of myocardial blood flow (MBF) quantification and impacts MBF accuracy but to an unclear extent. PURPOSE: To assess the impact of temporal resolution on quantitative perfusion and compare approaches for accounting for its variability. STUDY TYPE: Prospective phantom and retrospective clinical study. POPULATION AND PHANTOM: Simulations, a cardiac perfusion phantom, and 30 patients with (16, 53%) or without (14, 47%) coronary artery disease. FIELD STRENGTH/SEQUENCE: 3.0 T/2D saturation recovery spoiled gradient echo sequence. ASSESSMENT: Dynamic perfusion data were simulated for a range of reference MBF (1 mL/g/min-5 mL/g/min) and HR (30 bpm-150 bpm). Perfusion imaging was performed in patients and a phantom for different temporal resolutions. MBF and myocardial perfusion reserve (MPR) were quantified without correction for temporal resolution or following correction by either MBF scaling based on the sampling interval or data interpolation prior to quantification. Simulated data were quantified using Fermi deconvolution, truncated singular value decomposition, and one-compartment modeling, whereas phantom and clinical data were quantified using Fermi deconvolution alone. STATISTICAL TESTS: Shapiro-Wilk tests for normality, percentage error (PE) for measuring MBF accuracy in simulations, and one-way repeated measures analysis of variance with Bonferroni correction to compare clinical MBF and MPR. Statistical significance set at P < 0.05. RESULTS: For Fermi deconvolution and an example simulated 1 mL/g/min, the MBF PE without correction for temporal resolution was between 55.4% and -62.7% across 30-150 bpm. PE was between -22.2% and -6.8% following MBF scaling and between -14.2% and -14.2% following data interpolation across the same HR. An interpolated HR of 240 bpm reduced PE to ≤10%. Clinical rest and stress MBF and MPR were significantly different between analyses. DATA CONCLUSION: Accurate perfusion quantification needs to account for the variability of temporal resolution, with data interpolation prior to quantification reducing MBF variability across different resolutions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Influence of the arterial input sampling location on the diagnostic accuracy of cardiovascular magnetic resonance stress myocardial perfusion quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference. METHODS: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis. RESULTS: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717). CONCLUSIONS: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Pixel-wise assessment of cardiovascular magnetic resonance first-pass perfusion using a cardiac phantom mimicking transmural myocardial perfusion gradients.

PURPOSE: Cardiovascular magnetic resonance first-pass perfusion for the pixel-wise detection of coronary artery disease is rapidly becoming the clinical standard, yet no widely available method exists for its assessment and validation. This study introduces a novel phantom capable of generating spatially dependent flow values to enable assessment of new perfusion imaging methods at the pixel level. METHODS: A synthetic multicapillary myocardial phantom mimicking transmural myocardial perfusion gradients was designed and manufactured with high-precision 3D printing. The phantom was used in a stationary flow setup providing reference myocardial perfusion rates and was scanned on a 3T system. Repeated first-pass perfusion MRI for physiological perfusion rates between 1 and 4 mL/g/min was performed using a clinical dual-sequence technique. Fermi function-constrained deconvolution was used to estimate pixel-wise perfusion rate maps. Phase contrast (PC)-MRI was used to obtain velocity measurements that were converted to perfusion rates for validation of reference values and cross-method comparison. The accuracy of pixel-wise maps was assessed against simulated reference maps. RESULTS: PC-MRI indicated excellent reproducibility in perfusion rate (coefficient of variation [CoV] 2.4-3.5%) and correlation with reference values (R2 = 0.985) across the full physiological range. Similar results were found for first-pass perfusion MRI (CoV 3.7-6.2%, R2 = 0.987). Pixel-wise maps indicated a transmural perfusion difference of 28.8-33.7% for PC-MRI and 23.8-37.7% for first-pass perfusion, matching the reference values (30.2-31.4%). CONCLUSION: The unique transmural perfusion pattern in the phantom allows effective pixel-wise assessment of first-pass perfusion acquisition protocols and quantification algorithms before their introduction into routine clinical use.

Importance of operator training and rest perfusion on the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). METHODS: We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. RESULTS: Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34). CONCLUSIONS: Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.

Magnetic resonance imaging in experimental stroke and comparison with histology: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Because the new era of preclinical stroke research demands improvements in validity and generalizability of findings, moving from single site to multicenter studies could be pivotal. However, the conduct of magnetic resonance imaging (MRI) in stroke remains ill-defined. We sought to assess the variability in the use of MRI for evaluating lesions post stroke and to examine the possibility as an alternative to gold standard histology for measuring the infarct size. METHODS: We identified animal studies of ischemic stroke reporting lesion sizes using MRI. We assessed the degree of heterogeneity and reporting of scanning protocols, postprocessing methods, study design characteristics, and study quality. Studies performing histological evaluation of infarct size were further selected to compare with corresponding MRI using meta-regression. RESULTS: Fifty-four articles undertaking a total of 78 different MRI scanning protocols met the inclusion criteria. T2-weighted imaging was most frequently used (83% of the studies), followed by diffusion-weighted imaging (43%). Reporting of the imaging parameters was adequate, but heterogeneity between studies was high. Twelve studies assessed the infarct size using both MRI and histology at corresponding time points, with T2-weighted imaging-based treatment effect having a significant positive correlation with histology (; P<0.001). CONCLUSIONS: Guidelines for standardized use and reporting of MRI in preclinical stroke are urgently needed. T2-weighted imaging could be used as an effective in vivo alternative to histology for estimating treatment effects based on the extent of infarction; however, additional studies are needed to explore the effect of individual parameters.

Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology.

BACKGROUND: Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80). RESULTS: About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [P=0.03]) without compromising specificity (77% versus 74% [P=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted. CONCLUSIONS: CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension: A review.

Among five types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) is the only curable form, but prompt and accurate diagnosis can be challenging. Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH, however these are limited by radiation exposure, subjective qualitative bias, and lack of cardiac functional assessment. This review aims to assess the methodology, diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages, limitations and future research scope.

Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET.

BACKGROUND: Guidelines recommend verification of myocardial ischemia by selective second-line myocardial perfusion imaging (MPI) following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Head-to-head data on the diagnostic performance of different MPI modalities in this setting are sparse. OBJECTIVES: The authors sought to compare, head-to-head, the diagnostic performance of selective MPI by 3.0-T cardiac magnetic resonance (CMR) and 82rubidium positron emission tomography (RbPET) in patients with suspected obstructive stenosis at coronary CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. METHODS: Consecutive patients (n = 1,732, mean age: 59.1 ± 9.5 years, 57.2% men) referred for coronary CTA with symptoms suggestive of obstructive CAD were included. Patients with suspected stenosis were referred for both CMR and RbPET and subsequently ICA. Obstructive CAD was defined as FFR ≤0.80 or >90% diameter stenosis by visual assessment. RESULTS: In total, 445 patients had suspected stenosis on coronary CTA. Of these, 372 patients completed both CMR, RbPET and subsequent ICA with FFR. Hemodynamically obstructive CAD was identified in 164 of 372 (44.1%) patients. Sensitivities for CMR and RbPET were 59% (95% CI: 51%-67%) and 64% (95% CI: 56%-71%); P = 0.21, respectively, and specificities 84% (95% CI: 78%-89%) and 89% (95% CI: 84%-93%]); P = 0.08, respectively. Overall accuracy was higher for RbPET compared with CMR (73% vs 78%; P = 0.03). CONCLUSIONS: In patients with suspected obstructive stenosis at coronary CTA, CMR, and RbPET show similar and moderate sensitivities but high specificities compared with ICA with FFR. This patient group represents a diagnostic challenge with frequent mismatch between advanced MPI tests and invasive measurements. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712).

Simultaneous 13N-Ammonia and gadolinium first-pass myocardial perfusion with quantitative hybrid PET-MR imaging: a phantom and clinical feasibility study.

BACKGROUND: Positron emission tomography (PET) is the non-invasive reference standard for myocardial blood flow (MBF) quantification. Hybrid PET-MR allows simultaneous PET and cardiac magnetic resonance (CMR) acquisition under identical experimental and physiological conditions. This study aimed to determine feasibility of simultaneous 13N-Ammonia PET and dynamic contrast-enhanced CMR MBF quantification in phantoms and healthy volunteers. METHODS: Images were acquired using a 3T hybrid PET-MR scanner. Phantom study: MBF was simulated at different physiological perfusion rates and a protocol for simultaneous PET-MR perfusion imaging was developed. Volunteer study: five healthy volunteers underwent adenosine stress. 13N-Ammonia and gadolinium were administered simultaneously. PET list mode data was reconstructed using ordered subset expectation maximisation. CMR MBF was quantified using Fermi function-constrained deconvolution of arterial input function and myocardial signal. PET MBF was obtained using a one-tissue compartment model and image-derived input function. RESULTS: Phantom study: PET and CMR MBF measurements demonstrated high repeatability with intraclass coefficients 0.98 and 0.99, respectively. There was high correlation between PET and CMR MBF (r = 0.98, p < 0.001) and good agreement (bias - 0.85 mL/g/min; 95% limits of agreement 0.29 to - 1.98). Volunteer study: Mean global stress MBF for CMR and PET were 2.58 ± 0.11 and 2.60 ± 0.47 mL/g/min respectively. On a per territory basis, there was moderate correlation (r = 0.63, p = 0.03) and agreement (bias - 0.34 mL/g/min; 95% limits of agreement 0.49 to - 1.18). CONCLUSION: Simultaneous MBF quantification using hybrid PET-MR imaging is feasible with high test repeatability and good to moderate agreement between PET and CMR. Future studies in coronary artery disease patients may allow cross-validation of techniques.

Multicenter Evaluation of Geometric Accuracy of MRI Protocols Used in Experimental Stroke.

It has recently been suggested that multicenter preclinical stroke studies should be carried out to improve translation from bench to bedside, but the accuracy of magnetic resonance imaging (MRI) scanners routinely used in experimental stroke has not yet been evaluated. We aimed to assess and compare geometric accuracy of preclinical scanners and examine the longitudinal stability of one scanner using a simple quality assurance (QA) protocol. Six 7 Tesla animal scanners across six different preclinical imaging centers throughout Europe were used to scan a small structural phantom and estimate linear scaling errors in all orthogonal directions and volumetric errors. Between-scanner imaging consisted of a standard sequence and each center's preferred sequence for the assessment of infarct size in rat models of stroke. The standard sequence was also used to evaluate the drift in accuracy of the worst performing scanner over a period of six months following basic gradient calibration. Scaling and volumetric errors using the standard sequence were less variable than corresponding errors using different stroke sequences. The errors for one scanner, estimated using the standard sequence, were very high (above 4% scaling errors for each orthogonal direction, 18.73% volumetric error). Calibration of the gradient coils in this system reduced scaling errors to within ±1.0%; these remained stable during the subsequent 6-month assessment. In conclusion, despite decades of use in experimental studies, preclinical MRI still suffers from poor and variable geometric accuracy, influenced by the use of miscalibrated systems and various types of sequences for the same purpose. For effective pooling of data in multicenter studies, centers should adopt standardized procedures for system QA and in vivo imaging.