Myocardial Blood Flow Values Research Articles

Myocardial blood flow quantitation in patients with congestive heart failure: head-to-head comparison between rapid-rotating gantry SPECT and CZT SPECT

PurposeRecently, the feasibility of myocardial blood flow (MBF) quantitation using rapid-rotating gantry (RRG) and cadmium–zinc–telluride (CZT) SPECT cameras has been demonstrated. We compared MBF quantitation using these two camera systems. MethodsTwenty patients with congestive heart failure (CHF) and 20 patients without CHF (non-CHF) were included. On two consecutive days, dynamic SPECT imaging was performed after a bolus injection of 20 mCi of 99mTc-Sestamibi (MIBI) with RRG-SPECT and list-mode acquisition with CZT-SPECT. All dynamic SPECT images were reconstructed with full physical corrections, corrections for ventricular spillover and partial volume effect, using one-tissue kinetic modeling. Resting MBF converted from K1 was then corrected for MIBI extraction fraction and adjusted for rate-pressure product. ResultsIn both patient groups, there was no significant difference between resting MBF values measured with RRG-SPECT and CZT-SPECT systems (P = 0.06, P = 0.2 respectively). For CHF patients, linear regression (LR) was y(RRG) = 1.0412x (CZT) (r = 0.97) with a small systemic difference (Δ = 0.03 mL·min−1·g−1, 95% CI − 0.11 to 0.20) by Bland–Altman analysis. For non-CHF patients, LR was y(RRG) = 1.025x (CZT) (r = 0.89) with also small systemic difference (ΔT= 0.02 mL·min−1·g−1, 95% CI − 0.14 to 0.19) in BA analysis. ConclusionPhysical corrections along with other image corrections can provide comparable MBF quantitations in both CHF and non-CHF patients, regardless of the type of SPECT systems used.

Automated dynamic motion correction using normalized gradient fields for 82rubidium PET myocardial blood flow quantification

BackgroundPatient motion can lead to misalignment of left ventricular (LV) volumes-of-interest (VOIs) and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to develop an image-based 3D-automated motion-correction algorithm that corrects the full dynamic sequence for translational motion, especially in the early blood phase frames (~ first minute) where the injected tracer activity is transitioning from the blood pool to the myocardium and where conventional image registration algorithms have had limited success. MethodsWe studied 225 consecutive patients who underwent dynamic rest/stress rubidium-82 chloride (82Rb) PET imaging. Dynamic image series consisting of 30 frames were reconstructed with frame durations ranging from 5 to 80 seconds. An automated algorithm localized the RV and LV blood pools in space and time and then registered each frame to a tissue reference image volume using normalized gradient fields with a modification of a signed distance function. The computed shifts and their global and regional flow estimates were compared to those of reference shifts that were assessed by three physician readers. ResultsThe automated motion-correction shifts were within 5 mm of the manual motion-correction shifts across the entire sequence. The automated and manual motion-correction global MBF values had excellent linear agreement (R = 0.99, y = 0.97x + 0.06). Uncorrected flows outside of the limits of agreement with the manual motion-corrected flows were brought into agreement in 90% of the cases for global MBF and in 87% of the cases for global MFR. The limits of agreement for stress MBF were also reduced twofold globally and by fourfold in the RCA territory. ConclusionsAn image-based, automated motion-correction algorithm for dynamic PET across the entire dynamic sequence using normalized gradient fields matched the results of manual motion correction in reducing bias and variance in MBF and MFR, particularly in the RCA territory.

The detection of multivessel coronary artery disease: the value of quantitative myocardial blood flow and coronary flow reserve assessment

Abstract Background/Introduction The recent Cadmium-Zinc-Telluride (CZT) camera for MPS allows evaluating absolute MBF and CFR, possibly increasing the accuracy in detecting of multivessel CAD. Purpose To evaluate the accuracy of myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitation performed by myocardial perfusion scintigraphy (MPS) for the detection of multivessel coronary artery disease (CAD). Methods Fifty-two patients with suspected or known CAD were enrolled in the study. All patients underwent CZT MPS, with the evaluation of MBF and CFR, followed by invasive coronary angiography. According to MPS and coronary angiography results, patients were divided into three groups. 1) non-obstructive CAD and normal MPS scan (control group) (n=7), 2) one vessel disease (1VD) (n=16), with significant coronary stenosis (≥70%) in one major epicardial coronary artery, 3) multivessel disease (MVD) group (n=29), with two or more major epicardial coronary arteries with (≥70%) stenoses or with ≥50% LMA stenosis. Results Absolute MBF and CFR were significantly reduced in patients with MVD as compared to those with 1VD [0.93 (IQR 0.76; 1.39) vs 1.94 (1.37; 2.21) ml/min/g, p=0.00012] and [1.4 (IQR 1.02; 1.85) vs 2.3 (1.8; 2.67), p=0.0004], respectively. The Syntax score correlated with global stress MBF (ρ=−0.64; p<0.0001) and CFR (ρ=−0.53; p=0.0003). ROC analysis showed higher sensitivity and specificity for stress MBF (85.2% and 81%), and CFR (88.9% and 80%) compared with semiquantitative MPS stress evaluation (69% and 69%). Multivariate regression analysis showed that only stress MBF [OR (95% CI) 0.59 (0.42–0.82); p<0.0003] was an independent predictor of MVD. Conclusion The use of absolute myocardial blood flow analysis with the CZT camera may identify high risk patients, such as those with multivessel disease. This approach could be used in clinical practice, increasing the accuracy in the evaluation of patients with known or suspected coronary artery disease. Funding Acknowledgement Type of funding source: None

High-risk plaque burdens myocardial flow reserve in intermediate coronary artery disease: hybrid analysis of 13N-ammonia PET and coronary CT angiography

Abstract Background 13N-ammonia PET (NH3-PET) can detect myocardial perfusion abnormalities in patients with coronary artery disease (CAD) and also obtain diagnostic quantitative values of absolute myocardial blood flow and myocardial flow reserve (MFR). Low MFR (MFR<2.0) is an independent prognostic factor for major adverse cardiac event in patients with ischemic and non-ischemic heart disease. A feature of low attenuation plaque (LAP) on coronary CT angiography (CCTA) has been known as high-risk plaque (HRP) for acute coronary syndrome even if there is no significant coronary stenosis. The presence of HRP potentially adversely affects MFR, but the hypothesis has not been elucidated. Purpose We aimed to investigate the affect of LAP to MFR in intermediate CAD. Methods One hundred five patients (age 67±9 years, 65% male) with CAD underwent NH3-PET and CCTA within 6 months between April 2015 and March 2019 were enrolled. Based on the results of CCTA, mild and moderate stenosis were defined as 1% to 49% and 50% to 69% stenosis. Ischemic territories for major three vessels were identified by stress/rest NH3-PET images. Finally, 194 coronary arteries with mild to moderate stenosis corresponding to non-ischemic territory were analyzed in this study. LAP was defined as plaques containing CT value less than 90HU. Partially calcified plaques were included in LAP. Entirely calcification plaque without LAP was defined as calcified plaque. MFR for major three vessels were calculated from dynamic scan at stress/rest NH3-PET. Results CCTA showed 80 coronary arteries with LAP (41%), 104 coronary arteries with calcified plaque (54%), 102 vessels with mild stenosis (53%), and 92 vessels with moderate stenosis (47%). MFRs for coronary arteries with LAP were significantly lower than those without LAP (2.1±0.6 vs 2.5±0.6, p<0.0001). The significant difference in MFR between with and without LAP was observed in both mild and moderate stenosis (mild: 2.0±0.6 vs 2.5±0.6, p=0.0015, moderate: 2.1±0.6 vs 2.5±0.6, p<0.0001). In contrast, coronary arteries with calcified plaque had significantly higher MFR than those without (2.5±0.6 vs 2.1±0.6, p<0.0001). In 58 coronary arteries with MFR<2.0, 71% (41/58) had LAP and 24% (14/58) had calcified plaque. In 136 coronary arteries with MFR≥2.0, 29% (39/136) had LAP and 66% (90/136) had calcified plaque. LAP was significantly more frequent in the former and calcified plaque was significantly more frequent in the latter. Conclusion The presence of LAP burdens MFR in mild to moderate CAD. On the other hand, calcified plaque alone had no adverse effect on MFR. LAP is an important sign in CAD risk assessment even without significant coronary stenosis. MFR and stress MPI Funding Acknowledgement Type of funding source: None

Diagnostic performance of quantitative, semi-quantitative, and visual analysis of dynamic CT myocardial perfusion imaging: a validation study with invasive fractional flow reserve.

To investigate the diagnostic performance of absolute myocardial blood flow (MBF), MBFratio, and visual analysis of dynamic CT myocardial perfusion imaging (CT-MPI) for the detection of hemodynamically significant coronary stenosis. Consecutive patients with chest pain and intermediate-to-high pre-test probability of obstructive coronary artery disease were prospectively enrolled. All patients were referred for dynamic CT-MPI and fractional flow reserve (FFR) measurements within 4weeks. Absolute MBF, MBFratio (mean MBF of stenosis-subtended territories versus that of reference territories), and visually identified perfusion defect were tested for the diagnostic performance with reference to FFR. Sixty-two patients with 95 target vessels were included for final analysis. The mean radiation dose for dynamic CT-MPI was 3.0 (2.2-4.0) mSv. The mean lesion-based absolute MBF value was significantly lower in ischemic segments than that in non-ischemic segments (78.0 (65.0-86.0) mL/min/100mL vs. 133.0 (117.5-163.8) mL/min/100mL, p < 0.001). Similarly, the lesion-based MBFratio was also markedly lower in territories with positive FFR results (0.52 (0.44-0.64) vs. 0.93 (0.91-0.97), p < 0.001). According to per-lesion ROC curve analysis, MBF and MBFratio had a similar area under the curve (AUC) for detecting hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for MBF and 96.1%, 93.2%, and 94.7% for MBFratio. Absolute MBF and MBFratio had similarly excellent diagnostic performance with reference to FFR. In addition, these two parameters outperformed visual analysis for the detection of myocardial ischemia. • The mean MBF and MBFratio were significantly lower in ischemic segments than those in non-ischemic segments. • Absolute MBF and MBFratio had similar AUCs for the detection of hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). • The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBFratio.

Dynamic CT Myocardial Perfusion Imaging in Patients without Obstructive Coronary Artery Disease: Quantification of Myocardial Blood Flow according to Varied Heart Rate Increments after Stress.

ObjectiveThe present study aimed to investigate the association between myocardial blood flow (MBF) quantified by dynamic CT myocardial perfusion imaging (CT-MPI) and the increments in heart rate (HR) after stress in patients without obstructive coronary artery disease.Materials and MethodsWe retrospectively included 204 subjects who underwent both dynamic CT-MPI and coronary CT angiography (CCTA). Patients with more than minimal coronary stenosis (diameter ≥ 25%), history of myocardial infarction/revascularization, cardiomyopathy, and microvascular dysfunction were excluded. Global MBF at stress was measured using hybrid deconvolution and maximum slope model. Furthermore, the HR increments after stress were recorded.ResultsThe median radiation dose of dynamic CT-MPI plus CCTA was 5.5 (4.5–6.8) mSv. The median global MBF of all subjects was 156.4 (139.8–180.4) mL/100 mL/min. In subjects with HR increment between 10 to 19 beats per minute (bpm), the global MBF was significantly lower than that of subjects with increment between 20 to 29 bpm (153.3 mL/100 mL/min vs. 171.3 mL/100 mL/min, p = 0.027). This difference became insignificant when the HR increment further increased to ≥ 30 bpm.ConclusionThe global MBF value was associated with the extent of increase in HR after stress. Significantly higher global MBF was seen in subjects with HR increment of ≥ 20 bpm.

Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals

BackgroundHere we evaluated the feasibility of PET with Gallium-68 (68Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs. Methods8 healthy pigs underwent three sequential 68Ga-DOTA-PET/CT scans at rest and during pharmacological stress with simultaneous injection of fluorescent microspheres to validate MBF measurements. Myocardial infarction was induced in 5 additional pigs, which underwent 68Ga-DOTA-PET/CT examinations 7-days after reperfusion. Dynamic PET images were reconstructed and fitted to obtain MBF and ECV parametric maps. ResultsMBF assessed with 68Ga-DOTA-PET showed good correlation (y = 0.96x + 0.11, r = 0.91) with that measured with microspheres. MBF values obtained with 68Ga-DOTA-PET in the infarcted area (LAD, left anterior descendant) were significantly reduced in comparison to remote ones LCX (left circumflex artery, P < 0.0001) and RCA (right coronary artery, P < 0.0001). ECV increased in the infarcted area (P < 0.0001). Conclusion68Ga-DOTA-PET allowed non-invasive assessment of MBF and ECV in pigs with myocardial infarction and under rest-stress conditions. This technique could provide wide access to quantitative measurement of both MBF and ECV with PET imaging.

Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes

The objective of this study was to investigate the incremental prognostic value for adverse events of myocardial blood flow (MBF) derived from stress computed tomography perfusion (CTP) at remote myocardium over cardiac risk factors and ischemia. We prospectively analyzed 242 patients who underwent dynamic CTP and CT angiography. Adverse events were defined as a composite of all-cause mortality, non-fatal myocardial infarction, unstable angina, heart failure requiring hospitalization, peripheral artery disease, and stroke. MBF value was calculated in each myocardial segment and ischemia was defined as mild decrease in MBF in two consecutive segments or moderate decrease in a single segment accompanied with a coronary stenosis ≥50%. The mean MBF of the non-ischemic segments was defined as remote MBF. We divided the patients into two groups by median MBF value of 1.15 ml/min/g. During a median follow-up of 18 months, 18 patients had adverse events. Annual event rate showed a significant difference between patients with low (≤1.15 ml/min/g) and high (>1.15 ml/min/g) MBF (6.1% vs 1.8%, p = 0.02). Univariate analysis showed that low MBF was a significant predictor of events (hazard ratio (HR): 3.4; 95% confidence interval (CI): 1.2 to 12.0; p = 0.02). This relationship maintained significant after adjusted for the presence of ischemia and cardiac risk factors (HR: 3.0; 95%CI: 1.1 to 11.1; p = 0.04). In conclusion, MBF value ≤1.15 ml/min/g derived from dynamic CTP in remote myocardium is significantly related with poor outcome and this relationship was independent of myocardial ischemia and cardiac risk factors.

Whole-heart, ungated, free-breathing, cardiac-phase-resolved myocardial perfusion MRI by using Continuous Radial Interleaved simultaneous Multi-slice acquisitions at sPoiled steady-state (CRIMP).

To develop a whole-heart, free-breathing, non-electrocardiograph (ECG)-gated, cardiac-phase-resolved myocardial perfusion MRI framework (CRIMP; Continuous Radial Interleaved simultaneous Multi-slice acquisitions at sPoiled steady-state) and test its quantification feasibility. CRIMP used interleaved radial simultaneous multi-slice (SMS) slice groups to cover the whole heart in 9 or 12 short-axis slices. The sequence continuously acquired data without magnetization preparation, ECG gating or breath-holding, and captured multiple cardiac phases. Images were reconstructed by a motion-compensated patch-based locally low-rank reconstruction. Bloch simulations were performed to study the signal-to-noise ratio/contrast-to-noise ratio (SNR/CNR) for CRIMP and to study the steady-state signal under motion. Seven patients were scanned with CRIMP at stress and rest to develop the sequence. One human and two dogs were scanned at rest with a dual-bolus method to test the quantification feasibility of CRIMP. The dual-bolus scans were performed using both CRIMP and an ungated radial SMS saturation recovery (SMS-SR) sequence with injection dose = 0.075 mmol/kg to compare the sequences in terms of SNR, cardiac phase resolution and quantitative myocardial blood flow (MBF). Perfusion images with multiple cardiac phases in all image slices with a temporal resolution of 72ms/frame were obtained. Simulations and in-vivo acquisitions showed CRIMP kept the inner slices in steady-state regardless of motion. CRIMP outperformed SMS-SR in slice coverage (9 over 6), SNR (mean 20% improvement), and provided cardiac phase resolution. CRIMP and SMS-SR sequences provided comparable MBF values (rest systolic CRIMP = 0.58 ± 0.07, SMS-SR = 0.61 ± 0.16). CRIMP allows for whole-heart, cardiac-phase-resolved myocardial perfusion images without ECG-gating or breath-holding. The sequence can provide MBF if an accurate arterial input function is obtained separately.

Different Microcirculation Response Between Culprit and Non‐Culprit Vessels in Patients With Acute Coronary Syndrome

BackgroundThis study investigated whether the microvascular dysfunction differed between culprit and non‐culprit vessels in patients with acute coronary syndrome who underwent percutaneous coronary intervention.Methods and ResultsIn 115 prospectively recruited patients, after successful percutaneous coronary intervention, culprit and non‐culprit intracoronary hemodynamic measurements were performed and repeated at 6‐month follow‐up. 13N‐ammonia positron emission tomography was performed at 6‐month follow‐up visit to determine absolute myocardial blood flow. The resistance values of each vessel were calculated using the coronary pressure data and the myocardial blood flow values obtained from 13N‐ammonia positron emission tomography data. We compared the measurements between culprit and non‐culprit vessels and assessed changes in microvascular dysfunction during the study period. In 334 vessels (115 culprit and 219 non‐culprit), the culprit vessel group showed a lower fractional flow reserve and coronary flow reserve than the non‐culprit vessel group at baseline and 6‐month follow‐up, respectively. The value of index of microcirculatory resistance was different between the 2 groups in the baseline but not at 6‐month follow‐up. The microvascular resistance at rest and hyperemic microvascular resistance were not different between the 2 groups, but resistance to stenosis was higher in the culprit vessel group, under both resting and hyperemic status (P=0.02 and P<0.01, respectively). In the culprit vessel analysis, the fractional flow reserve and index of microcirculatory resistance decreased whereas coronary flow reserve increased (P<0.01 for all) at 6‐month follow‐up. However, there was no change in index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve from baseline to 6‐month follow‐up in the non‐culprit vessel analysis.ConclusionsThe observed microvascular dysfunction in acute coronary syndrome is limited to the culprit vessel territory in the acute phase, which is relatively recovered in the chronic phase and there is no out‐of‐culprit territory involvement.RegistrationURL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04169516.

Accelerated Wideband Myocardial Perfusion Pulse Sequence with Compressed Sensing Reconstruction for Myocardial Blood Flow Quantification in Patients with a Cardiac Implantable Electronic Device.

To develop an accelerated wideband cardiac perfusion pulse sequence and test whether it can produce diagnostically acceptable image quality and whether it can be used to reliably quantify myocardial blood flow (MBF) in patients with a cardiac implantable electronic device (CIED). A fivefold-accelerated wideband perfusion pulse sequence was developed using compressed sensing to sample one arterial input function plane and three myocardial perfusion (MP) planes per heartbeat in patients with a CIED with heart rates as high as 102 beats per minute. Resting perfusion scans were performed in 10 patients with a CIED and in 10 patients with no device as a control group. Two clinical readers compared the resulting images and retrospective images of the 10 patients with a CIED, which were obtained by using a previously described twofold-accelerated wideband perfusion pulse sequence with temporal generalized autocalibrating partially parallel acquisition. Summed visual score (SVS) was defined as the sum of conspicuity, artifact, and noise scores individually ranging from 1 (worst) to 5 (best). Resting MBF in the remote zones was quantified using Fermi deconvolution. Median SVS was significantly different (P < .05) between the prospective and retrospective CIED groups (13 vs nine) and between the nondevice group and the retrospective CIED group (13.5 vs nine); all median SVSs were nine or greater (clinically acceptable cut point). The median resting MBF in remote zones was not significantly different (P = .27) between patients with a CIED (1.1 mL/min/g; median left ventricular ejection fraction [LVEF], 52.5%) and patients with no device (1.3 mL/min/g; median LVEF, 64.0%). Mean MBF values were consistent with those (mean resting MBF range, 1.0-1.2 mL/min/g) reported by two prior state-of-the-art cardiac perfusion MRI studies. The proposed scan yielded diagnostically acceptable image quality and enabled reliable quantification of MBF with three MP planes per heartbeat in patients with a CIED with heart rates as high as 102 beats per minute. Supplemental material is available for this article. © RSNA, 2020.

Prognostic implication of global myocardial blood flow in patients with ST-segment elevation myocardial infarction.

The prognostic implications of cardiovascular magnetic resonance imaging (CMR)-derived hyperemic myocardial blood flow (MBF) in patients with ST-elevation myocardial infarction (STEMI) are unknown. This study sought to investigate the incremental prognostic value of hyperemic MBF over conventional CMR markers to identify patients with high risk of future incidence of patient-oriented composite outcomes (POCO) and major adverse cardiac events (MACE) after STEMI. A total of 237 patients who presented with STEMI were prospectively enrolled. The CMR protocol included left-ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE) and microvascular obstruction (MVO) measurement, and volumetric MBF assessment. During a median follow-up of 2.6years, 47 patients experienced POCO (primary outcome) and 21 patients had MACE. In a multivariable model, multivessel disease, LGE, MVO, and hyperemic MBF were independently associated with POCO. Addition of hyperemic MBF to the model consisting of GRACE score, multivessel disease, LVEF, LGE, and MVO significantly improved the predictive efficacy (integrated discrimination improvement 0.020, p = 0.021). Patients with low hyperemic MBF had significantly higher incidence of MACE compared to those with high hyperemic MBF inpropensity score matching analysis (p = 0.018). In conclusion, CMR-derived hyperemic MBF could provide independent and incremental prognostic value over LVEF, LGE, and MVO in patients with STEMI.

The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012–2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making.

Stress dynamic myocardial CT perfusion for symptomatic patients with intermediate- or high-risk of coronary artery disease: Optimization and incremental improvement between the absolute and relative myocardial blood flow analysis

BackgroundThe optimization of myocardial CT perfusion (CTP) assessment remains inconsistent and uncertain. Our aim was to explore the superior analysis selection and incremental improvement of myocardial blood flow (MBF) assessment on CTP in diagnosing hemodynamically significant coronary artery disease (CAD). MethodsSixty patients (43 men and 17 women; 61.38 ± 8.01 years) were prospectively recruited and underwent stress dynamic myocardial CTP examinations. Absolute and relative MBF was used for ischemia evaluation with the invasive coronary angiography and fractional flow reserve were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) and cutoff values were calculated and compared. ResultsThere were 151 vessels in 60 patients finally enrolled for analysis. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for the absolute MBF value and relative MBF ratio were 82.76%, 98.92%, 97.96%, 90.20%, and 92.72% and 74.14%, 93.56%, 87.76%, 85.29%, and 86.09%, respectively. The absolute MBF value was superior than the relative MBF ratio in detecting ischemia (AUC, 0.955 [95%CI: 0.919–0.990] vs.0.906 [95%CI:0.857–0.954])(P = 0.02). For territories with both sensitivity and specificity ≤90%, the diagnostic accuracy increased from 79.1% to 88.4% when the specific data were assessed using the absolute MBF value instead of the relative MBF ratio. ConclusionsThe absolute MBF value from the endocardial myocardium on stress dynamic myocardial CTP showed superior diagnostic performance compared to the relative MBF ratio for the detection of myocardial ischemia in intermediate-to-high risk patients. The absolute MBF value provides an incremental benefit toward diagnostic performance for the relative MBF ratio evaluation.

Enhanced external counterpulsation improves cardiac function in Beagles after cardiopulmonary resuscitation.

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies.

We previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3. Nine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images. In the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained. This study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

Intersoftware variability impacts classification of cardiac PET exams

BackgroundMyocardial perfusion imaging (MPI) with 82Rb PET/CT is increasingly utilized in the evaluation of coronary artery disease with high diagnostic accuracy. Various softwares for data processing have been developed over the years with conflicting data regarding their reproducibility. In this study, we compared the quantitative results of myocardial perfusion and exam classification from three different softwares. MethodsData from consecutive patients who have undergone rest/stress 82Rb PET/CT MPI at the Royal Brompton & Harefield Trust, London, were analyzed. All data were processed using the Corridor 4DM (Invia, Ann Arbor, Michigan, USA), QPET (Cedars-Sinai, Los Angeles, California, USA), and SyngoMBF (Siemens Healthineers, Erlangen, Germany). The software packages addressed Lortie tracer kinetic model and region of interest (ROI) extraction correction option. StatisticsA repeated-measures ANOVA with a Greenhouse–Geisser correction was performed with post hoc tests using Bonferroni correction. For intersoftware variability, Pearson correlation and intraclass correlation coefficients (ICC) were calculated. Bland–Altman assessed limit of agreement. Cohen’s Kappa assessed agreement in the classification of exams as normal or abnormal using an MFR cut-off value of 2.0. A P value of less than 0.05 was considered statistically significant. ResultsData from 55 patients were analyzed. The mean values of myocardial blood flow (MBF) and myocardial perfusion reserve (MFR) were statistically significantly different among the softwares (P < 0.05). Corridor4DM had considerably lower values of MFR and classified a more substantial number of exams as abnormal (MFR: 2.21 ± 0.7, 2.4 ± 0.8, and 1.98 ± 0.8; and 18, 15, and 31 exams were abnormal for Syngo, QPET, and Corridor4DM, respectively). Accordingly, kappa agreement was moderate for Syngo vs QPET (k > 0.5), but minimal for Corridor4DM in comparison to its pairs (k < 0.4). ConclusionUsers should be cautious when using different software interchangeably as systematic differences amongst them may introduce more extensive quantitative variation which could be clinically significant.

Deep-Learning-Based Preprocessing for Quantitative Myocardial Perfusion MRI.

BackgroundQuantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particularly the segmentation.PurposeTo evaluate the efficacy of an automated deep learning (DL) pipeline for image processing prior to quantitative analysis.Study TypeRetrospective.PopulationIn all, 175 (350 MRI scans; 1050 image series) clinical patients under both rest and stress conditions (135/10/30 training/validation/test).Field Strength/Sequence3.0T/2D multislice saturation recovery T1‐weighted gradient echo sequence.AssessmentAccuracy was assessed, as compared to the manual operator, through the mean square error of the distance between landmarks and the Dice similarity coefficient of the segmentation and bounding box detection. Quantitative perfusion maps obtained using the automated DL‐based processing were compared to the results obtained with the manually processed images.Statistical TestsBland–Altman plots and intraclass correlation coefficient (ICC) were used to assess the myocardial blood flow (MBF) obtained using the automated DL pipeline, as compared to values obtained by a manual operator.ResultsThe mean (SD) error in the detection of the time of peak signal enhancement in the left ventricle was 1.49 (1.4) timeframes. The mean (SD) Dice similarity coefficients for the bounding box and myocardial segmentation were 0.93 (0.03) and 0.80 (0.06), respectively. The mean (SD) error in the RV insertion point was 2.8 (1.8) mm. The Bland–Altman plots showed a bias of 2.6% of the mean MBF between the automated and manually processed MBF values on a per‐myocardial segment basis. The ICC was 0.89, 95% confidence interval = [0.87, 0.90].Data ConclusionWe showed high accuracy, compared to manual processing, for the DL‐based processing of myocardial perfusion data leading to quantitative values that are similar to those achieved with manual processing. Level of Evidence: 3 Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2020;51:1689–1696.

Myocardial blood flow analysis of stress dynamic myocardial CT perfusion for hemodynamically significant coronary artery disease diagnosis: The clinical value of relative parameter optimization

BackgroundThe methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards. MethodsA total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation. ResultsA total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ± 8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P < 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857–0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P < 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675. ConclusionsThe relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.

3332Exercise training ameliorates vasodilator capacity of coronary microvessels in patients with vasospastic angina - A new therapeutic approach for the coronary functional disorder

Abstract Background We have recently demonstrated that coronary vasospasm could develop in both epicardial coronary arteries and intramuscular coronary microvessels in patients with vasospastic angina (VSA). However, it remains to be examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients and if so, whether exercise training could ameliorate vasodilator capacity of coronary microvessels on the top of calcium channel blockers. The effectiveness of exercise training is established for organic coronary artery disease but remained to be examined for VSA. Purpose We thus examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients without organic coronary stenosis using an adenosine-stress dynamic computed tomography perfusion (CTP) that can measure absolute value of myocardial blood flow (MBF). We also examined whether exercise training ameliorates not only vasodilator capacity of coronary microvessels but also exercise capacity and frequency of angina attack. Methods In the first protocol, we measured MBF using CTP in consecutive 32 VSA patients with acetylcholine-induced diffuse coronary spasm in the left anterior descending coronary arteries (LAD) and 12 non-VSA controls. In the second protocol, we conducted a randomized controlled trial (RCT; Exercise VSA trial, UMIN: ehz745.008423996), where 20 VSA patients were randomly assigned to either exercise group (Ex group: supervised exercise training session for 30-min using bicycle ergometer, once/week at the hospital and more than 3 times/week at home) or non-exercise group (Non-Ex group) (n=10 each) (Figure A). Before and 3 months after exercise training, we measured MBF with adenosine-stress dynamic CTP and peak VO2 by cardiopulmonary exercise tests, and also assessed angina attack with Seattle Angina Questionnaire (SAQ). Results In the first protocol, CTP showed that adenosine-stress MBF was significantly decreased in the VSA group compared with the non-VSA group (VSA, 137.2±6.6 vs. Non-VSA, 174.4±10.7 ml/100g/min, P&lt;0.01) (Figure B), although patient characteristics were comparable between the 2 groups. In the second protocol, exercise training was performed safely in all patients, and RCT showed that MBF was significantly increased in the Ex group compared with the non-Ex group (Figures C, D), although patient characteristics were also comparable between the 2 groups. Furthermore, peak VO2 was significantly increased in the Ex group compared with the non-Ex group (Figure E), and frequency of angina was significantly decreased in the Ex group compared with the non-Ex group (Figure F). Finally, there was a significant positive correlation between the extents of the changes in peak VO2 and the SAQ score for angina frequency in the Ex group (P&lt;0.01, R=0.67). Figures Conclusions These results provide the first evidence that vasodilator capacity of coronary microvessels is impaired in VSA patients, which can be ameliorated by exercise training.