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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 p p 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.

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.

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.

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 ( .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.

The arterial input function (AIF) describes the contrast agent input to the myocardium and is required for perfusion quantification ([1][1]). Cardiovascular magnetic resonance quantitative perfusion analysis typically uses the basal left ventricular (LV) blood pool to sample the AIF, despite this

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): British Heart Foundation Background Coronary artery bypass grafting (CABG) is an established treatment for patients with advanced coronary artery disease (CAD). A subsequent recurrence of symptoms can cause the need for re-assessment of the coronary circulation. The accuracy of visually assessed stress perfusion cardiovascular magnetic resonance (CMR) for the detection of obstructive CAD is reduced in patients with prior CABG. In patients with complex multi-vessel CAD, myocardial perfusion quantification by CMR is superior to visual assessment (VA) for detection of obstructive disease however patients with CABG have been absent from previous studies. Purpose This study sought to assess the performance of myocardial perfusion quantification by CMR against invasive coronary angiography (ICA) for detecting obstructive CAD in patients with previous CABG. Methods Twenty-nine patients with a history of previous CABG and subsequent clinically indicated perfusion CMR study and invasive coronary angiography were recruited. Patients underwent a dual bolus stress perfusion CMR with late gadolinium enhancement (LGE) imaging at 3 Tesla. Stress myocardial blood flow (MBF) was estimated at the coronary territory level according to the AHA 16 segment model using Fermi function-constrained deconvolution. Segments with transmural LGE were excluded from MBF analysis. Stress perfusion images were analysed visually alongside LGE images and matched perfusion-LGE defects were considered negative. On ICA, coronary territories with lumen stenosis >70% without an unobstructed bypass graft ( Results 86/87 coronary territories were suitable for analysis. Sixty-five territories had at least one bypass graft including 32 territories with arterial grafts. 28/86 territories (33%) had obstructive disease on angiography. Territories with obstructive CAD had significantly lower stress MBF than unobstructed territories (1.21 [IQR: 0.96–1.45] vs 1.58 [1.40–1.84] ml/g/min, p < 0.001, Figure 1). Stress MBF had good accuracy to detect coronary territories with obstructive CAD (sensitivity 71%, specificity 84%, area under the curve (AUC) 0.83, p < 0.001, Figure 2A). For visual assessment, sensitivity was 79%, specificity 78% and diagnostic accuracy 78%. When analysis was confined to only territories with bypass grafts, stress MBF had 78% sensitivity, 81% specificity and AUC of 0.85, p < 0.001 (Figure 2B).. In this subgroup, VA had a sensitivity of 78%, specificity of 76% and a 77% diagnostic accuracy. Conclusions In patients with previous surgical revascularisation, quantification of stress myocardial blood flow by CMR offers good diagnostic accuracy for the detection and localisation of anatomically significant stenoses. Accuracy is reduced compared with published data in patients without coronary grafts but remains comparable to expert visual assessment.

In the medical sector, various imaging methodologies or modalities (e.g. MRI, PET, CT) are used to assess the health of various parts of the bodies of patients. One such investigation is the blood flow or perfusion of the heart muscle, expressed as the (blood) flow rate normalized by the mass of the volume of interest. Currently there is no physical flow standard for the validation of quantitative perfusion measurements. This need has been addressed in the EMPIR 15HLT05 PerfusImaging project. A phantom simulating the heart muscle has been developed with the capability that it can reproducibly generate a flow profile with individual flow rates known with a relative uncertainty of about 10% (k = 2) and total flow rate known with an uncertainty of 1% (k = 2). An overview of the phantom and its validation is given. Next, a new analysis method is presented to analyse the sequence of images which are acquired when using a standard dynamic imaging protocol. It is concluded that the new, alternative approach gives results comparable to the standard analysis method.

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

Objective To determine whether a change in editorial policy, including the implementation of a checklist, has been associated with improved reporting of measures which might reduce the risk of bias.Methods The study protocol has been published at doi: 10.1007/s11192-016-1964-8.Design Observational cohort study.Population Articles describing research in the life sciences published in Nature journals, submitted after 1 May 2013.Intervention Mandatory completion of a checklist during manuscript revision.Comparators (1) Articles describing research in the life sciences published in Nature journals, submitted before May 2013; and (2) similar articles in other journals matched for date and topic.Primary outcome The primary outcome is change in the proportion of Nature articles describing in vivo research published before and after May 2013 reporting the ‘Landis 4’ items (randomisation, blinding, sample size calculation and exclusions). We included 448 Nature Publishing Group (NPG) articles (223 published before May 2013, and 225 after) identified by an individual hired by NPG for this specific task, working to a standard procedure; and an independent investigator used PubMed ‘Related Citations’ to identify 448 non-NPG articles with a similar topic and date of publication from other journals; and then redacted all articles for time-sensitive information and journal name. Redacted articles were assessed by two trained reviewers against a 74-item checklist, with discrepancies resolved by a third.Results 394 NPG and 353 matching non-NPG articles described in vivo research. The number of NPG articles meeting all relevant Landis 4 criteria increased from 0/203 prior to May 2013 to 31/181 (16.4%) after (two-sample test for equality of proportions without continuity correction, Χ²=36.2, df=1, p=1.8×10−9). There was no change in the proportion of non-NPG articles meeting all relevant Landis 4 criteria (1/164 before, 1/189 after). There were more substantial improvements in the individual prevalences of reporting of randomisation, blinding, exclusions and sample size calculations for in vivo experiments, and less substantial improvements for in vitro experiments.Conclusion There was an improvement in the reporting of risks of bias in in vivo research in NPG journals following a change in editorial policy, to a level that to our knowledge has not been previously observed. However, there remain opportunities for further improvement.This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

Details of the perfusion phantom. (DOCX 513 kb)

Introduction Myocardial scar and ischaemia frequently coexist in patients with ischaemic heart failure (IHF). In clinical practice, stress-perfusion (SP) is assessed visually together with late gadolinium enhancement (LGE) images, however the feasibility of simultaneous LGE and SP quantification has only been recently demonstrated (Villa, JCMR 2016). The aim of this study was to apply a fully quantitative method combining scar and perfusion to the challenging cohort of patient with IHF. Methods Consecutive patients with IHF (LVEF Results 161 patients were included (LVEF 33.5±9.8). 93% had evidence of flow-limiting CAD on angiography, 42.9% demonstrated three-vessels disease. The ischaemic burden detected with visual assessment (9.4%) was significantly lower compared to the ischaemic burden detected with quantitative methods. Moreover, there was an overestimation when not considering LGE. Visual assessment underestimates the extent of ischaemia; quantitative high-resolution combined method correctly identifies more patients as having three-vessel disease. The methods were tested against invasive coronary angiography and there was evidence of a better performance of the quantitative methods on a per-patient level, with a significantly better performance of quantitative combined high-resolution on a per-vessel level. Conclusion Our study showed that a fully quantitative approach enables accurate assessment of the ischaemic burden, without overestimation due to LGE, and that with this method we identify more patient with ischaemia in all coronary territories. Moreover, this study demonstrated that visual assessment, which is used routinely in clinical practice, tends to underestimate the extent of ischaemic in patient with IHF. In conclusion, high-resolution combined quantification should be used to avoid overlap between areas of scar and ischaemia, allowing a more precise assessment of the true ischaemic burden.

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. T 2 -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 T 2 -weighted imaging–based treatment effect having a significant positive correlation with histology ( ; P Conclusions— Guidelines for standardized use and reporting of MRI in preclinical stroke are urgently needed. T 2 -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.

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.