Mean Myocardial Blood Flow Research Articles

Optimal repetition time for free breathing myocardial arterial spin labeling.

The aim of this study was to improve the scan efficiency of ASL in the myocardium. Free breathing FAIR-ASL scans with different TRs were compared, while keeping the acquisition time constant. Scans were named by the trigger pulse that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. TP2 offered the best alternative with a coefficient of variation of 17.15% intrasession and 36.85% intersession. Mean MBF increased by 0.22±0.41ml/g/min with mild stress.

Impact of regadenoson-induced myocardial creep on dynamic Rubidium-82 PET myocardial blood flow quantification

BackgroundRepositioning of the heart during myocardial perfusion imaging (MPI) using Rubidium-82 (Rb-82) PET may occur when using regadenoson. Our aim was to determine the prevalence and the effect of correcting for this myocardial creep on myocardial blood flow (MBF) quantification. MethodsWe retrospectively included 119 consecutive patients who underwent dynamic rest- and regadenoson-induced stress MPI using Rb-82 PET. The presence of myocardial creep was visually assessed in the dynamic stress PET series by identifying differences between the automatically drawn myocardium contour and the activity. Uncorrected and corrected stress MBFs were compared for the three vascular territories (LAD, LCX, and RCA) and for the whole myocardium. ResultsMyocardial creep was observed in 52% of the patients during stress. Mean MBF values decreased after correction in the RCA from 4.0 to 2.7 mL/min/g (P < 0.001), in the whole myocardium from 2.7 to 2.6 mL/min/g (P = 0.01), and increased in the LAD from 2.5 to 2.6 mL/min/g (P = 0.03) and remained comparable in the LCX (P = 0.3). ConclusionsMyocardial creep is a frequent phenomenon when performing regadenoson-induced stress Rb-82 PET and has a significant impact on MBF values, especially in the RCA territory. As this may hamper diagnostic accuracy, myocardial creep correction seems necessary for reliable quantification.

Prevalence of Decreased Myocardial Blood Flow in Symptomatic Patients with Patent Coronary Stents: Insights from Low-Dose Dynamic CT Myocardial Perfusion Imaging.

To study the prevalence and clinical characteristics of decreased myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) in symptomatic patients without in-stent restenosis. Thirty-seven (mean age, 71.3 ± 10 years; age range, 48-88 years; 31 males, 6 females) consecutive symptomatic patients with patent coronary stents and without obstructive de novo lesions were prospectively enrolled to undergo dynamic CT-MPI using a third-generation dual-source CT scanner. The shuttle-mode acquisition technique was used to image the complete left ventricle. A bolus of contrast media (50 mL; iopromide, 370 mg iodine/mL) was injected into the antecubital vein at a rate of 6 mL/s, followed by a 40-mL saline flush. The mean MBF value and other quantitative parameters were measured for each segment of both stented-vessel territories and reference territories. The MBFratio was defined as the ratio of the mean MBF value of the whole stent-vessel territory to that of the whole reference territory. An MBFratio of 0.85 was used as the cut-off value to distinguish hypoperfused from non-hypoperfused segments. A total of 629 segments of 37 patients were ultimately included for analysis. The mean effective dose of dynamic CT-MPI was 3.1 ± 1.2 mSv (range, 1.7-6.3 mSv). The mean MBF of stent-vessel territories was decreased in 19 lesions and 81 segments. Compared to stent-vessel territories without hypoperfusion, the mean MBF and myocardial blood volume were markedly lower in hypoperfused stent-vessel territories (77.5 ± 16.6 mL/100 mL/min vs. 140.4 ± 24.1 mL/100 mL/min [p < 0.001] and 6.4 ± 3.7 mL/100 mL vs. 11.5 ± 4 mL/100 mL [p < 0.001, respectively]). Myocardial hypoperfusion in stent-vessel territories was present in 48.6% (18/37) of patients. None of clinical parameters differed statistically significantly between hypoperfusion and non-hypoperfusion subgroups. Decreased MBF is commonly present in patients who are symptomatic after percutaneous coronary intervention, despite patent stents and can be detected by dynamic CT-MPI using a low radiation dose.

Impact of individualized segmentation on diagnostic performance of quantitative positron emission tomography for haemodynamically significant coronary artery disease.

Despite high variability in coronary anatomy, quantitative positron emission tomography (PET) perfusion in coronary territories is traditionally calculated according to the American Heart Association (AHA) 17-segments model. This study aimed to assess the impact of individualized segmentation of myocardial segments on the diagnostic accuracy of hyperaemic myocardial blood flow (MBF) values for haemodynamically significant coronary artery disease (CAD). Patients with suspected CAD (n = 204) underwent coronary computed tomography angiography (CCTA) and [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve assessment of all major coronary arteries. Hyperaemic MBF per vascular territory was calculated using both standard segmentation according to the AHA model and individualized segmentation, in which CCTA was used to assign coronary arteries to PET perfusion territories. In 122 (59.8%) patients, one or more segments were redistributed after individualized segmentation. No differences in mean MBF values were seen between segmentation methods, except for a minor difference in hyperaemic MBF in the LCX territory (P = 0.001). These minor changes resulted in discordant PET-defined haemodynamically significant CAD between the two methods in only 5 (0.8%) vessels. The diagnostic value for detecting haemodynamically significant CAD did not differ between individualized and standard segmentation, with area under the curves of 0.79 and 0.78, respectively (P = 0.34). Individualized segmentation using CCTA-derived coronary anatomy led to redistribution of standard myocardial segments in 60% of patients. However, this had little impact on [15O]H2O PET MBF values and diagnostic value for detecting haemodynamically significant CAD did not change. Therefore, clinical impact of individualized segmentation seems limited.

Accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, compressed sensing, and k-space weighted image contrast reconstruction tailored for visual analysis and quantification of myocardial blood flow.

To develop an accelerated cardiac perfusion pulse sequence and test whether it is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of myocardial blood flow (MBF). We implemented an accelerated first-pass cardiac perfusion pulse sequence by combining radial k-space sampling, compressed sensing (CS), and k-space weighted image contrast (KWIC) filtering. The proposed and clinical standard pulse sequences were evaluated in a randomized order in 13 patients at rest. For visual analysis, 3 readers graded the conspicuity of wall enhancement, artifact, and noise level on a 5-point Likert scale (overall score index = sum of 3 individual scores). Resting MBF was calculated using a Fermi function model with and without KWIC filtering. Mean visual scores and MBF values were compared between sequences using appropriate statistical tests. The proposed pulse sequence produced greater spatial coverage (6-8 slices) with higher spatial resolution (1.6 × 1.6 × 8 mm3 ) and shorter readout duration (78 ms) compared to clinical standard (3-4 slices, 3 × 3 × 8 mm3 , 128 ms, respectively). The overall image score index between accelerated (11.1 ± 1.3) and clinical standard (11.2 ± 1.3) was not significantly different (P = 0.64). Mean resting MBF values with KWIC filtering (0.9-1.2 mL/g/min across different slices) were significantly lower (P < 0.0001) than those without KWIC filtering (3.1-4.3 mL/g/min) and agreed better with values reported in literature. An accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, CS, and KWIC filtering is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of MBF.

Myocardial blood flow and myocardial flow reserve values in 13N\u2013ammonia myocardial perfusion PET/CT using a time-efficient protocol in patients without coronary artery disease

BackgroundCardiac imaging by means of myocardial Positron Emission Tomography/Computed Tomography (PET/CT) is being used increasingly to assess coronary artery disease, to guide revascularization decisions with more accuracy, and it allows robust quantitative analysis of both regional myocardial blood flow (MBF) and myocardial flow reserve (MFR).Recently, a more time-efficient protocol has been developed in combination with a residual activity correction algorithm in which a stress acquisition is performed directly after completion of the rest acquisition to subtract remaining myocardial radioactivity.The objective of this study is to define flow values of myocardial blood flow (MBF) and Myocardial Flow Reserve (MFR) with 13N–ammonia (13NH3) myocardial perfusion PET/CT on patients without coronary artery disease using a time-efficient protocol, since reference values for this particular type of study are lacking in literature. In addition, we aim to determine the effect of the residual activity correction algorithm in this time-efficient protocol.ResultsA mean MBF in rest of 1.02 ± 0.22 ml/g/min, a mean MBF in stress of 2.54 ± 0.41 ml/g/min with a mean MFR of 2.60 ± 0.61 were measured. Female patients had a significant higher MBF in rest and stress, but lower MFR; a small but significant negative correlation was measured between age and MBF in stress and MFR. Residual activity correction had a significant effect resulting in a difference in global stress MBF before and after correction of 0.39 ± 0.13 ml/g/min.ConclusionsThis study established flow values for 13NH3 myocardial PET/CT with a time-efficient protocol, and established that MBF in stress corrected for residual activity is comparable with known reference values in normal studies without temporal overlap. Further validation of the technique could be of value, e.g. by comparison to standard imaging without temporal overlap, or validation against catheterization results.

Rapid computation of single PET scan rest-stress myocardial blood flow parametric images by table look up.

We have recently reported a method for measuring rest-stress myocardial blood flow (MBF) using a single, relatively short, PET scan session. The method requires two IV tracer injections, one to initiate rest imaging and one at peak stress. We previously validated absolute flow quantitation in ml/min/cc for standard bull's eye, segmental analysis. In this work, we extend the method for fast computation of rest-stress MBF parametric images. We provide an analytic solution to the single-scan rest-stress flow model which is then solved using a two-dimensional table lookup method (LM). Simulations were performed to compare the accuracy and precision of the lookup method with the original nonlinear method (NLM). Then the method was applied to 16 single scan rest/stress measurements made in 12 pigs: seven studied after infarction of the left anterior descending artery (LAD) territory, and nine imaged in the native state. Parametric maps of rest and stress MBF as well as maps of left (fLV ) and right (fRV ) ventricular spill-over fractions were generated. Regions of interest (ROIs) for 17 myocardial segments were defined in bull's eye fashion on the parametric maps. The mean of each ROI was then compared to the rest (K1r ) and stress (K1s ) MBF estimates obtained from fitting the 17 regional TACs with the NLM. In simulation, the LM performed as well as the NLM in terms of precision and accuracy. The simulation did not show that bias was introduced by the use of a predefined two-dimensional lookup table. In experimental data, parametric maps demonstrated good statistical quality and the LM was computationally much more efficient than the original NLM. Very good agreement was obtained between the mean MBF calculated on the parametric maps for each of the 17 ROIs and the regional MBF values estimated by the NLM (K1mapLM =1.019×K1ROINLM +0.019, R2 =0.986; mean difference=0.034±0.036mL/min/cc). We developed a table lookup method for fast computation of parametric imaging of rest and stress MBF. Our results show the feasibility of obtaining good quality MBF maps using modest computational resources, thus demonstrating that the method can be applied in a clinical environment to obtain full quantitative MBF information.

Single-scan rest/stress imaging: validation in a porcine model with 18F-Flurpiridaz.

18F-labeled myocardial flow agents are becoming available for clinical application but the ∼2hour half-life of 18F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15minutes. Single-scan rest-stress measurements were made using 18F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4minutes after the first injection of 18F-Flurpiridaz and followed either 3 or 6minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull's eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously. The first 12-14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035ml/min/cc. Mean myocardial blood flow across pigs was 0.61 ± 0.11mL/min/cc at rest and 1.06 ± 0.19mL/min/cc at stress in healthy pigs and 0.36 ± 0.20mL/min/cc at rest and 0.62 ± 0.24mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope = 1.061 ± 0.017, intercept = 0.051 ± 0.017, mean difference 0.096 ± 0.18ml/min/cc). Accurate rest and stress blood flow estimation can be obtained in less than 15min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

Classification of hemodynamically significant stenoses from dynamic CT perfusion and CTA myocardial territories.

Myocardial blood flow (MBF) obtained by dynamic CT perfusion (CTP) has been recently introduced to assess hemodynamic significance of coronary stenosis in coronary artery disease. The diagnostic performance of dynamic CTP MBF is limited due to subjective interpretation of MBF maps and MBF variations caused by physiological, methodological, and technical issues. In this paper, we introduce a novel method to quantify the hypoperfused volume (HPV) in myocardial territories derived from CT angiography (CTA) to overcome the limitations of current dynamic CTP MBF analysis methods. The diagnostic performance of HPV in classifying significant stenoses was evaluated on 22 patients (57 vessels) that underwent CTA, CTP and invasive fractional flow reserve (FFR). FFR was used as the standard of reference to determine stenosis significance. The diagnostic performance was compared to that of the mean MBF computed in regions manually annotated by an expert (MA-MBF). HPV was derived by thresholding the MBF in myocardial territories constructed from CTA by locating the closest artery. Diagnostic performance was evaluated using leave-one-case out cross-validation. Inter-observer reproducibility was assessed by performing annotations of coronary seeds (HPV) and manual regions (MA-MBF) with two users. In addition, the influence of different parameter settings on the diagnostic performance of HPV was assessed. Leave-one-case out cross-validation showed that HPV has an accuracy of 72% (58-83%) with sensitivity of 72% (47-90%) and specificity of 72% (58-83%). The accuracy of MA-MBF was 70% (57-82%) with a sensitivity of 50% (26-74%) and a specificity of 79% (64-91%). The Spearman correlation and the kappa statistic was (ρ = 0.94, κ = 0.86) for HPV and (ρ = 0.72, κ = 0.82) for MA-MBF. The influence of parameter settings on HPV based diagnostic performance was not significant. The proposed HPV accurately classifies hemodynamically significant stenoses with a level of accuracy comparable to the mean MBF in regions annotated by an expert. HPV improves inter-observer reproducibility as compared to MA-MBF by providing a more objective criterion to associate the stenotic coronary with the supplied myocardial territory.

Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR

BackgroundThe use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46–74 years) with known or suspected coronary artery disease underwent 15O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values.ResultsStress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00.ConclusionsPET-MR-based MBF values correlated well with PET-CT-based MBF values and the parametric PET-MR images were excellent. TOF and reconstruction settings had little impact on MBF values.

Impact of motion and partial volume effects correction on PET myocardial perfusion imaging using simultaneous PET-MR

PET is an established modality for myocardial perfusion imaging (MPI) which enables quantification of absolute myocardial blood flow (MBF) using dynamic imaging and kinetic modeling. However, heart motion and partial volume effects (PVE) significantly limit the spatial resolution and quantitative accuracy of PET MPI. Simultaneous PET-MR offers a solution to the motion problem in PET by enabling MR-based motion correction of PET data. The aim of this study was to develop a motion and PVE correction methodology for PET MPI using simultaneous PET-MR, and to assess its impact on both static and dynamic PET MPI using 18F-Flurpiridaz, a novel 18F-labeled perfusion tracer.Two dynamic 18F-Flurpiridaz MPI scans were performed on healthy pigs using a PET-MR scanner. Cardiac motion was tracked using a dedicated tagged-MRI (tMR) sequence. Motion fields were estimated using non-rigid registration of tMR images and used to calculate motion-dependent attenuation maps. Motion correction of PET data was achieved by incorporating tMR-based motion fields and motion-dependent attenuation coefficients into image reconstruction. Dynamic and static PET datasets were created for each scan. Each dataset was reconstructed as (i) Ungated, (ii) Gated (end-diastolic phase), and (iii) Motion-Corrected (MoCo), each without and with point spread function (PSF) modeling for PVE correction. Myocardium-to-blood concentration ratios (MBR) and apparent wall thickness were calculated to assess image quality for static MPI. For dynamic MPI, segment- and voxel-wise MBF values were estimated by non-linear fitting of a 2-tissue compartment model to tissue time-activity-curves.MoCo and Gating respectively decreased mean apparent wall thickness by 15.1% and 14.4% and increased MBR by 20.3% and 13.6% compared to Ungated images (P < 0.01). Combined motion and PSF correction (MoCo-PSF) yielded 30.9% (15.7%) lower wall thickness and 82.2% (20.5%) higher MBR compared to Ungated data reconstructed without (with) PSF modeling (P < 0.01). For dynamic PET, mean MBF across all segments were comparable for MoCo (0.72 ± 0.21 ml/min/ml) and Gating (0.69 ± 0.18 ml/min/ml). Ungated data yielded significantly lower mean MBF (0.59 ± 0.16 ml/min/ml). Mean MBF for MoCo-PSF was 0.80 ± 0.22 ml/min/ml, which was 37.9% (25.0%) higher than that obtained from Ungated data without (with) PSF correction (P < 0.01).The developed methodology holds promise to improve the image quality and sensitivity of PET MPI studies performed using PET-MR.

Quantitative Perfusion Analysis of First-Pass Contrast Enhancement Kinetics: Application to MRI of Myocardial Perfusion in Coronary Artery Disease.

PurposePerfusion analysis from first-pass contrast enhancement kinetics requires modeling tissue contrast exchange. This study presents a new approach for numerical implementation of the tissue homogeneity model, incorporating flexible distance steps along the capillary (NTHf).MethodsThe proposed NTHf model considers contrast exchange in fluid packets flowing along the capillary, incorporating flexible distance steps, thus allowing more efficient and stable calculations of the transit of tracer through the tissue. We prospectively studied 8 patients (62 ± 13 years old) with suspected CAD, who underwent first-pass perfusion CMR imaging at rest and stress prior to angiography. Myocardial blood flow (MBF) and myocardial perfusion reserve index (MPRI) were estimated using both the NTHf and the conventional adiabatic approximation of the TH models. Coronary artery lesions detected at angiography were clinically assigned to one of three categories of stenosis severity (‘insignificant’, ‘mild to moderate’ and ‘severe’) and related to corresponding myocardial territories.ResultsThe mean MBF (ml/g/min) at rest/stress and MPRI were 0.80 ± 0.33/1.25 ± 0.45 and 1.68 ± 0.54 in the insignificant regions, 0.74 ± 0.21/1.09 ± 0.28 and 1.54 ± 0.46 in the mild to moderate regions, and 0.79 ± 0.28/0.63 ± 0.34 and 0.85 ± 0.48 in the severe regions, respectively. The correlation coefficients of MBFs at rest/stress and MPRI between the NTHf and AATH models were r = 0.97/0.93 and r = 0.91, respectively.ConclusionsThe proposed NTHf model allows efficient quantitative analysis of the transit of tracer through tissue, particularly at higher flow. Results of initial application to MRI of myocardial perfusion in CAD are encouraging.

Quantification of myocardial blood flow with (82)Rb: Validation with (15)O-water using time-of-flight and point-spread-function modeling.

BackgroundWe quantified myocardial blood flow with 82Rb PET using parameters of the generalized Renkin-Crone model estimated from 82Rb and 15O-water images reconstructed with time-of-flight and point spread function modeling. Previous estimates of rubidium extraction have used older-generation scanners without time-of-flight or point spread function modeling. We validated image-derived input functions with continuously collected arterial samples.MethodsNine healthy subjects were scanned at rest and under pharmacological stress on the Siemens Biograph mCT with 82Rb and 15O-water PET, undergoing arterial blood sampling with each scan. Image-derived input functions were estimated from the left ventricle cavity and corrected with tracer-specific population-based scale factors determined from arterial data. Kinetic parametric images were generated from the dynamic PET images by fitting the one-tissue compartment model to each voxel’s time activity curve. Mean myocardial blood flow was determined from each subject’s 15O-water k2 images. The parameters of the generalized Renkin-Crone model were estimated from these water-based flows and mean myocardial 82Rb K1 estimates.ResultsImage-derived input functions showed improved agreement with arterial measurements after a scale correction. The Renkin-Crone model fit (a = 0.77, b = 0.39) was similar to those previously published, though b was lower.ConclusionsWe have presented parameter estimates for the generalized Renkin-Crone model of extraction for 82Rb PET using human 82Rb and 15O-water PET from high-resolution images using a state-of-the-art time-of-flight-capable scanner. These results provide a state-of-the-art methodology for myocardial blood flow measurement with 82Rb PET.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0215-6) contains supplementary material, which is available to authorized users.

Effect of Outflow Tract Contributions to 82Rb-PET Global Myocardial Blood Flow Computations.

Algorithms are able to compute myocardial blood flow (MBF) from dynamic PET data for each of the 17 left ventricular segments, with global MBF obtained by averaging segmental values. This study was undertaken to compare MBFs with and without the basal-septal segments. Data were examined retrospectively for 196 patients who underwent rest and regadenoson-stress (82)Rb PET/CT scanning for evaluation of known or suspected coronary artery disease. MBF data were acquired in gated list mode and rebinned to isolate the first-pass dynamic portion. Coronary vascular resistance (CVR) was computed as mean arterial pressure divided by MBF. MBF inhomogeneity was computed as the ratio of SD to mean MBF. Relative perfusion scores were obtained using (82)Rb-specific normal limits applied to polar maps of myocardial perfusion generated from myocardial equilibrium portions of PET data. MBF and CVRs from 17 and 14 segments were compared. Mean MBFs were lower for 17- than 14-segment means for rest (0.78 ± 0.50 vs. 0.85 ± 0.54 mL/g/min, paired t test P < 0.0001) and stress (1.50 ± 0.88 vs. 1.67 ± 0.96 mL/g/min, P < 0.0001). Bland-Altman plots of MBF differences versus means exhibited nonzero intercept (-0.04 ± 0.01, P = 0.0004) and significant correlation (r = -0.64, P < 0.0001), with slopes significantly different from 0.0 (-7.2% ± 0.6% and -8.3% ± 0.7% for rest and stress MBF; P < 0.0001). Seventeen-segment CVRs were higher than 14-segment CVRs for rest (159 ± 86 vs. 147 ± 81 mm Hg/mL/g/min, paired t test P < 0.0001) and stress CVR (85 ± 52 vs. 76 ± 48 mm Hg/mL/g/min, P < 0.0001). MBF inhomogeneity correlated significantly (P < 0.0001) with summed perfusion scores, but values correlated significantly more strongly for 14- than 17-segment values for rest (r = 0.67 vs. r = 0.52, P = 0.02) and stress (r = 0.69 vs. r = 0.47, P = 0.001). When basal segments were included in MBF determinations, perfusion inhomogeneity was greater both for rest (39% ± 10% vs. 31% ± 10%, P < 0.0001) and for stress (42% ± 12% vs. 32% ± 11%, P < 0.0001). Averaging 17 versus 14 segments leads to systematically 7%-8% lower MBF calculations, higher CVRs, and greater computed inhomogeneity. Consideration should be given to excluding basal-septal segments from standard global MBF determination.

Reduced dose measurement of absolute myocardial blood flow using dynamic SPECT imaging in a porcine model.

Absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements provide important additional information over traditional relative perfusion imaging. Recent advances in camera technology have made this possible with single-photon emission tomography (SPECT). Low dose protocols are desirable to reduce the patient radiation risk; however, increased noise may reduce the accuracy of MBF measurements. The authors studied the effect of reducing dose on the accuracy of dynamic SPECT MBF measurements. Nineteen 30-40 kg pigs were injected with 370 + 1110 MBq of Tc-99m sestamibi or tetrofosmin or 37 + 111 MBq of Tl-201 at rest + stress. Microspheres were injected simultaneously to measure MBF. The pigs were imaged in list-mode for 11 min starting at the time of injection using a Discovery NM 530c camera (GE Healthcare). Each list file was modified so that 3/4, 1/2, 1/4, 1/8, 1/16, and 1/32 of the original counts were included in the projections. Modified projections were reconstructed with CT-based attenuation correction and an energy window-based scatter correction and analyzed with FlowQuant kinetic modeling software using a 1-compartment model. A modified Renkin-Crone extraction function was used to convert the tracer uptake rate K1 to MBF values. The SPECT results were compared to those from microspheres. Correlation between SPECT and microsphere MBF values for the full injected activity was r ≥ 0.75 for all 3 tracers and did not significantly degrade over all count levels. The mean MBF and MFR and the standard errors in the estimates were not significantly worse than the full-count data at 1/4-counts (Tc99m-tracers) and 1/2-counts (Tl-201). Dynamic SPECT measurement of MBF and MFR in pigs can be performed with 1/4 (Tc99m-tracers) or 1/2 (Tl-201) of the standard injected activity without significantly reducing accuracy and precision.

Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET.

Absolute quantitation of myocardial blood flow (MBF) by PET is an established method of analyzing coronary artery disease (CAD) but subject to the various shortcomings of available radiotracers. Flurpiridaz F 18 is a novel PET radiotracer that exhibits properties of an ideal tracer. A new absolute perfusion quantitation method with flurpiridaz was developed, taking advantage of the early kinetics and high first-pass extraction by the myocardium of this radiotracer, and the first-in-human measurements of MBF performed in 7 healthy subjects and 8 patients with documented CAD. PET images with time-activity curves were acquired at rest and during adenosine stress. In healthy subjects, regional MBF between coronary artery territories did not differ significantly, leading to a mean global MBF of 0.73 mL/min/g at rest and 2.53 mL/min/g during stress, with a mean global myocardial flow reserve (MFR) of 3.70. CAD vascular territories with <50% stenosis demonstrated a mean MBF of 0.73 at rest and 2.02 during stress, leading to a mean MFR of 2.97. CAD vascular territories with ≥50% stenosis exhibited a mean MBF of 0.86 at rest and 1.43 during stress, leading to a mean MFR of 1.86. Differences in stress MBF and MFR between normal and CAD territories, as well as between <50% and ≥50% stenosis vascular territories, were significant (P < 0.01). Absolute quantitation of MBF in humans with the novel PET radiotracer flurpiridaz is feasible over a wide range of cardiac flow in the presence or absence of stress-inducible myocardial ischemia. The significant decrease in stress MBF and ensuing MFR in CAD territories allows a clear distinction between vascular territories exhibiting stress-inducible myocardial ischemia and those with normal perfusion.

0276: Dynamics of the perfusion reserve during adenosine-induced stress in rats

In clinical routine, myocardial perfusion MRI is generally performed with a stress/rest protocol using adenosine as a short living (10s half-life) stressor. Adenosine allows visualizing ischemic risk zones in the myocardium and is typically injected 3 to 4 minutes prior to stress imaging. To gain insight into perfusion dynamics under stress, we used a non-invasive and fast imaging procedure (cine-ASL) to study the longitudinal effect of a continuous injection of adenosine on myocardial blood flow (MBF) and MBF reserve in rats. MBF and MBF reserve were monitored every 5min following adenosine injection (140μg/kg/min) on 17 healthy Wistar rats at 4.7T. For the Stress group (N=6), adenosine was continuously injected for 40min. For the Stress/Recovery group (N=6), adenosine was injected for 25min and then stopped for the last 15min. Finally, for the Control group (N=7), a saline solution was injected for 40 min. Mean group MBF at rest was 5.4±0.5mL/g/min in a ROI covering the entire myocardium. Mean group MBF data are reported as a function of time after onset of adenosine (Fig). In every studied animal of the 2 first groups subjected to stress, an initial MBF increase was found within the first 5min following adenosine infusion. But, the maximum MBF response to adenosine was always obtained later, between 5-10min, followed by a continuous MBF decrease until 25min. Maximum stress perfusion was 10.8±1.4mL/g/min leading to a reserve of 2.1±0.3, consistent with previously reported study. This study focuses on MBF response dynamics to adenosine. In rats, maximum MBF response to adenosine was found between 5 to 10min. Such dynamic measurements give more detailed insight into rodent coronary reserve and coronary responses to infused vasodilators and may give complementary information on microvascular functional defects in non-ischemic heart disease models.

0397: Age-related changes in rodent myocardial perfusion reserve in response to adenosine: longitudinal follow up with ASL-MRI

In clinical routine, myocardial perfusion MRI is generally performed with a stress/rest protocol using adenosine as a stressor to visualize ischemic risk zones in the myocardium. Changes in the vasodilator responses to adenosine with age have been reported in the rat thoracic aorta and the isolated- perfused rat heart. This study assesses the effect of maturation on the vascular relaxant action of adenosine in vivo on rats. We used a fast imaging procedure (cine-ASL) to non-invasively quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) at rest and during adenosine-induced stress. Adenosine was injected via the tail vein at a rate of 420 μg/kg/min. MBF and maximal MPR were monitored on 10 healthy Wistar rats at 4.7T, from young to mature rats at five different time points during growth (2, 8, 10, 13, and 15 months). Myocardial perfusion was measured in a region of interest covering the entire myocardium. No statistical differences in mean group MBF at rest were found across time (5.3±0.6 mL/g/min). MPR, defined as the ration of stress MBF over rest MBF, was 2.3±0.3 at M2, 2.2±0.4 at M8, 2.0±0.5 at M10, 1.7±0.3 at M13, and 1.7±0.2 at M15 (Fig.1). In rats, maximum MPR to adenosine was found to be at early stage of growth, while a continuous decrease in coronary response was observed as the animals became mature (significantly different at M13 and M15). This study focuses on age-related changes in coronary response to adenosine as an infused vasodilator. These changes might be due to alterations in the adenosine receptor sites and a decrease in vascular elasticity. Such measurements give more detailed insight into changes of rodent coronary reserve occurring with growth and are of interest for studying myocardial stress response in rodent heart disease models across time.

In vivo characterization of rodent cyclic myocardial perfusion variation at rest and during adenosine-induced stress using cine-ASL cardiovascular magnetic resonance.

BackgroundAssessment of cyclic myocardial blood flow (MBF) variations can be an interesting addition to the characterization of microvascular function and its alterations. To date, totally non-invasive in vivo methods with this capability are still lacking. As an original technique, a cine arterial spin labeling (ASL) cardiovascular magnetic resonance approach is demonstrated to be able to produce dynamic MBF maps across the cardiac cycle in rats.MethodHigh-resolution MBF maps in left ventricular myocardium were computed from steady-state perfusion-dependent gradient-echo cine images produced by the cine-ASL sequence. Cyclic changes of MBF over the entire cardiac cycle in seven normal rats were analyzed quantitatively every 6ms at rest and during adenosine-induced stress.ResultsThe study showed a significant MBF increase from end-systole (ES) to end-diastole (ED) in both physiological states. Mean MBF over the cardiac cycle within the group was 5.5 ± 0.6 mL g-1 min-1 at rest (MBFMin = 4.7 ± 0.8 at ES and MBFMax = 6.5 ± 0.6 mL g-1 min-1 at ED, P = 0.0007). Mean MBF during adenosine-induced stress was 12.8 ± 0.7mL g-1 min-1 (MBFMin = 11.7±1.0 at ES and MBFMax = 14.2 ± 0.7 mL g-1 min-1 at ED, P = 0.0007). MBF percentage relative variations were significantly different with 27.2 ± 9.3% at rest and 17.8 ± 7.1% during adenosine stress (P = 0.014). The dynamic analysis also showed a time shift of peak MBF within the cardiac cycle during stress.ConclusionThe cyclic change of myocardial perfusion was examined by mapping MBF with a steady-pulsed ASL approach. Dynamic MBF maps were obtained with high spatial and temporal resolution (6ms) demonstrating the feasibility of non-invasively mapping cyclic myocardial perfusion variation at rest and during adenosine stress. In a pathological context, detailed assessment of coronary responses to infused vasodilators may give valuable complementary information on microvascular functional defects in disease models.

Impact of errors in determining the start of myocardial enhancement during quantitative first pass perfusion cardiovascular magnetic resonance imaging

Background Several studies have shown the potential of semi-quantitative and fully-quantitative analysis of cardiovascular magnetic resonance (CMR) perfusion images in the diagnosis of coronary artery disease (CAD). However, estimates of myocardial blood flow (MBF) rely on accurate selection of important timing parameters. In this study, we evaluate how the identification of the timing of the Start of Myocardial Enhancement (SME) affects MBF quantification. We hypothesize that incorrectly selecting the SME can adversely affect quantification of the MBF. Methods 20 patients, including 10 with significant CAD (defined as ≥70% stenosis of a major epicardial artery on invasive coronary angiography), underwent regadenoson stress perfusion imaging using a steady-state free precession dual sequence technique followed by rest perfusion imaging. Motion corrected CMR perfusion images were quantified using model constrained deconvolution to obtain MBF estimates (in mL/min/g). Manual selection of SME was used as a reference start time. To evaluate how the timing of SME affects MBF, we systematically and intentionally shifted SME before and after the reference start time (-2, -1.5, -1, -0.5, 0.5, 1, 1.5, 2 second offsets were evaluated). A normal and a stenotic sector were identified from the myocardial signal intensity curves for each study with significant CAD. Results A SME ≥1 second later than the reference SME resulted in a significant overestimation of MBF (p < 0.001), with mean MBF ≥25% than with the reference SME except in the normal sector for rest. The later SME was shifted, the more MBF was overestimated. Delaying SME by 2 seconds led to MBF estimates up to 3 times higher than when the reference SME was used (Figure 1). In both normal (Figure 1) and stenotic sectors, a SME 0.5 second after the reference resulted in significantly higher (p < 0.001) stress and rest MBF values. However, a SME 1.0 second or more before the reference SME didn’t result in significant change of MBF estimates in both stress and rest studies (p = NS for both normal and stenotic sectors). Conclusions