Quantitative Perfusion Maps Research Articles

Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR

ObjectivesThe purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR. BackgroundPulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption. MethodsIn this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters. ResultsA total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002). ConclusionsPulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.

Use of quantitative cardiovascular magnetic resonance myocardial perfusion mapping for characterization of ischemia in patients with left internal mammary coronary artery bypass grafts

BackgroundQuantitative myocardial perfusion mapping using cardiovascular magnetic resonance (CMR) is validated for myocardial blood flow (MBF) estimation in native vessel coronary artery disease (CAD). Following coronary artery bypass graft (CABG) surgery, perfusion defects are often detected in territories supplied by the left internal mammary artery (LIMA) graft, but their interpretation and subsequent clinical management is variable.MethodsWe assessed myocardial perfusion using quantitative CMR perfusion mapping in 38 patients with prior CABG surgery, all with angiographically-proven patent LIMA grafts to the left anterior descending coronary artery (LAD) and no prior infarction in the LAD territory. Factors potentially determining MBF in the LIMA–LAD myocardial territory, including the impact of delayed contrast arrival through the LIMA graft were evaluated.ResultsPerfusion defects were reported on blinded visual analysis in the LIMA–LAD territory in 27 (71%) cases, despite LIMA graft patency and no LAD infarction. Native LAD chronic total occlusion (CTO) was a strong independent predictor of stress MBF (B = − 0.41, p = 0.014) and myocardial perfusion reserve (MPR) (B = − 0.56, p = 0.005), and was associated with reduced stress MBF in the basal (1.47 vs 2.07 ml/g/min; p = 0.002) but not the apical myocardial segments (1.52 vs 1.87 ml/g/min; p = 0.057). Extending the maximum arterial time delay incorporated in the quantitative perfusion algorithm, resulted only in a small increase (3.4%) of estimated stress MBF.ConclusionsPerfusion defects are frequently detected in LIMA–LAD subtended territories post CABG despite LIMA patency. Although delayed contrast arrival through LIMA grafts causes a small underestimation of MBF, perfusion defects are likely to reflect true reductions in myocardial blood flow, largely due to proximal native LAD disease.

Cardiovascular magnetic resonance detects microvascular dysfunction in a mouse model of hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) related myocardial vascular remodelling may lead to the reduction of myocardial blood supply and a subsequent progressive loss of cardiac function. This process has been difficult to observe and thus their connection remains unclear. Here we used non-invasive myocardial blood flow sensitive CMR to show an impairment of resting myocardial perfusion in a mouse model of naturally occurring HCM.MethodsWe used a mouse model (DBA/2 J; D2 mouse strain) that spontaneously carries variants in the two most susceptible HCM genes—Mybpc3 and Myh7 and bears the key features of human HCM. The C57BL/6 J (B6) was used as a reference strain. Mice with either B6 or D2 backgrounds (male: n = 4, female: n = 4) underwent cine-CMR for functional assessment at 9.4 T. Left ventricular (LV) wall thickness was measured in end diastolic phase by cine-CMR. Quantitative myocardial perfusion maps (male: n = 5, female: n = 5 in each group) were acquired from arterial spin labelling (cine ASL-CMR) at rest. Myocardial perfusion values were measured by delineating different regions of interest based on the LV segmentation model in the mid ventricle of the LV myocardium. Directly after the CMR, the mouse hearts were removed for histological assessments to confirm the incidence of myocardial interstitial fibrosis (n = 8 in each group) and small vessel remodelling such as vessel density (n = 6 in each group) and perivascular fibrosis (n = 8 in each group).ResultsLV hypertrophy was more pronounced in D2 than in B6 mice (male: D2 LV wall thickness = 1.3 ± 0.1 mm vs B6 LV wall thickness = 1.0 ± 0.0 mm, p < 0.001; female: D2 LV wall thickness = 1.0 ± 0.1 mm vs B6 LV wall thickness = 0.8 ± 0.1 mm, p < 0.01). The resting global myocardial perfusion (myocardial blood flow; MBF) was lower in D2 than in B6 mice (end-diastole: D2 MBFglobal = 7.5 ± 0.6 vs B6 MBFglobal = 9.3 ± 1.6 ml/g/min, p < 0.05; end-systole: D2 MBFglobal = 6.6 ± 0.8 vs B6 MBFglobal = 8.2 ± 2.6 ml/g/min, p < 0.01). This myocardial microvascular dysfunction was observed and associated with a reduction in regional MBF, mainly in the interventricular septal and inferior areas of the myocardium. Immunofluorescence revealed a lower number of vessel densities in D2 than in B6 (D2 capillary = 31.0 ± 3.8% vs B6 capillary = 40.7 ± 4.6%, p < 0.05). Myocardial collagen volume fraction (CVF) was significantly higher in D2 LV versus B6 LV mice (D2 CVF = 3.7 ± 1.4% vs B6 CVF = 1.7 ± 0.7%, p < 0.01). Furthermore, a higher ratio of perivascular fibrosis (PFR) was found in D2 than in B6 mice (D2 PFR = 2.3 ± 1.0%, B6 PFR = 0.8 ± 0.4%, p < 0.01).ConclusionsOur work describes an imaging marker using cine ASL-CMR with a potential to monitor vascular and myocardial remodelling in HCM.

Abstract P46: Baseline Characteristics of Patients With Cerebral Cavernous Angiomas With Symptomatic Hemorrhage in a Multisite Trial Readiness Study

Background: Patients with cerebral cavernous angiomas with symptomatic hemorrhage (CASH) have high risk of disability from recurrent bleeding. Candidate medications to prevent rebleeding in CASH lesions will require multisite clinical trials with standardized data collection. Objective: To report the prevalence and baseline cohort features in CASH patients and establish a research network infrastructure for trials. Methods: This prospective observational cohort study includes adults with radiologically verified CASH lesion within 1-year of consent. Exclusions include prior or planned surgical intervention, spinal location, or prior brain irradiation. Six sites enrolled patients into the screening and clinical assessment portion of the study starting July 2018. Patients also had the option to participate in the follow up biomarker validation at 4 sites. Baseline demographics, clinical and imaging information, and outcomes (mRS, PROMIS-29, NIHSS, and EuroQol-5D) were collected. Biomarker imaging included dynamic contrast enhanced quantitative perfusion (DCEQP) and quantitative susceptibility mapping (QSM) that correlated with symptomatic bleeding. Descriptive statistics were performed and one-sample t-test was used to compare whether mean T-scores for PROMIS-29 domains differed significantly from a reference population. Results: As of May 2020, 849 CASH patients were screened of whom 110 (13%) were eligible and enrolled; 73 also enrolled into the biomarker validation study. Average age at enrollment was 46±16 years at a mean of 4.4 months after symptom onset; 53% were female, 41% were familial, and 43% of CASH lesions were brainstem location. At enrollment, 90% of the cohort had independent functional outcome (mRS ≤ 2 and NIHSS &lt;5). Perceived health problems affecting QoL were reported in &gt;30% (EuroQol-5D). CASH cases had significantly worse anxiety but better depression and social satisfaction scores compared to a general population (all P&lt;0.01). Baseline DCEQP and QSM measures did not differ significantly across sites. Conclusion: We demonstrate feasibility of multisite recruitment of CASH patients and report prevalence of baseline features that will aid in design of clinical trials and inclusion of appropriate outcome measures.

Use of quantitative myocardial perfusion mapping by CMR for characterisation of ischaemia in patients post coronary artery bypass graft surgery

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Quantitative myocardial perfusion mapping using Cardiac Magnetic Resonance (CMR) imaging is used for evaluation of ischaemia in the context of native vessel coronary disease, but its diagnostic performance in patients with grafts is not well established. Perfusion defects are often detected in these patients, but whether these are a consequence of a technical limitation (delayed contrast arrival from graft conduits) or a true reflection of reduced myocardial blood flow is unclear. Methods 39 patients undergoing stress perfusion CMR with previous coronary artery bypass graft (CABG) surgery, unobstructed left internal mammary artery (LIMA) grafts to the left anterior descending (LAD) artery on coronary angiography and no CMR evidence of prior LAD infarction were included. Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were evaluated with quantitative perfusion mapping and the factors determining MBF in the LIMA-LAD territory (AHA segments 1,2,7,8,13,14), including the impact of delayed contrast arrival through the LIMA graft were evaluated. Results In 28 out of 39 cases a myocardial perfusion defect was reported on visual assessment in LIMA-LAD myocardial territory, despite the presence of unobstructed LIMA graft and no LAD infarction. Chronic total occlusion (CTO) of the native LAD was an independent predictor of stress MBF (B=-0.36, p =0.027) and the strongest predictor of MPR (B=-0.55, p 0.005) within the LIMA-LAD myocardial territory after adjusting for age, left ventricular (LV) ejection fraction, and presence of diabetes. CTO of the native LAD was associated with a reduction in stress MBF in the basal myocardial segments (-0.57ml/g/min, p = 0.002) but had no effect on the MBF of apical segments (-0.31ml/g/min, p = 0.084). Increasing the maximum value for allowable arterial delay (TA) of contrast in the quantitative mapping algorithm resulted in a small increase in myocardial blood flow in the LIMA-LAD territory both at stress (0.07 ± 0.08ml/g/min, p &amp;lt; 0.001) and rest (0.06 ± 0.05ml/g/min, p &amp;lt; 0.001). Conclusions Perfusion defects detected in LIMA-LAD subtended territories are common despite graft patency. These defects are likely to represent genuine reduction in MBF, resulting from native LAD coronary occlusion. Prolonged contrast transit time associated with LIMA grafts results in small underestimation of MBF as measured by quantitative CMR perfusion mapping, but does not account for the degree of MBF reduction seen in these patients. Figure 1. Study patient with unobstructed LIMA to LAD graft and evidence of inducible perfusion defect in LIMA-LAD territories. (A): First pass perfusion CMR imaging. (B): Perfusion mapping showing reduced stress MBF in mid antero-septum (0.85ml/g/min) compared to the apical septum (1.65ml/g/min). (C): Late gadolinium enhancement showing no evidence of previous infarction. (D,E): Coronary angiography demonstrating unobstructed LIMA graft (D) and anastomosis site (E). Abstract Figure 1.

Impact of obesity on myocardial microvasculature assessed using fully-automated inline myocardial perfusion mapping CMR

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospitals Biomedical Research Centre Background Obesity and cardiovascular disease are associated, but the relationship is poorly understood. Myocardial perfusion, metabolic derangement and lipotoxicity appear adversely associated in many scenarios (myocardial injury, diastolic dysfunction, diabetes). Altered perfusion (by PET) predicts outcome, and it is hypothesised that perfusion derangement is part of causality for cardiac disease and adverse outcomes. Purpose To assess the presence and pattern of myocardial microvascular dysfunction in patients with obesity (scheduled for bariatric surgery) using stress quantitative perfusion mapping. Methods 38 subjects with obesity planned to undergo bariatric surgery and 38 age and sex matched healthy volunteers (no diabetes, no hypertension) underwent anthropometry, biochemistry and CMR at 1.5T (Siemens) with cine imaging, stress (adenosine 140-210 mcg/kg/min) and rest fully-automated quantitative perfusion mapping. Results Bariatric patients had a higher BMI (44 ± 6.4 vs 26.5 ± 4kg/m2 p = 0.001); 58%(22) were diabetic and 58%(22) had hypertension. Bariatric patients had higher absolute but lower indexed end-diastolic volumes, and overall higher ejection fractions (+5%) (see Table). Rest myocardial blood flow (MBF) in bariatric patients was the same (1.00 ± 0.3 vs 0.88 ± 0.24 p = 0.052), but stress perfusion results were significantly lower both for stress MBF (2.35 ± 0.69 vs 2.93 ± 0.76ml/g/min p = 0.001) and myocardial perfusion reserve (MPR 2.48 ± 0.82 vs 3.4 ± 0.81ml/g/min p = 0.0001). Although this was transmural, the endocardial stress MBF was particularly negatively affected in the bariatric cohort compared to controls (endocardial MBF 2.16 ± 0.65 vs 2.82 ± 0.73ml/g/min, p = 0.0001 vs epicardial MBF: 2.52 ± 0.76 vs 3.06 ± 0.79 p = 0.003), meaning there was an increased endo-epicardial stress MBF gradient in bariatric patients (0.87 ± 0.12 vs 0.92 ± 0.07 p = 0.03). Conclusion Compared to healthy controls, patients with obesity have abnormal myocardial stress perfusion with reduced global perfusion, perfusion reserve and an increased transmyocardial perfusion gradient. Table - myocardial perfusion parameters Category Bariatric patients n = 38 Controls n = 38 p value Age (years) 48 ± 11 45 ± 13 0.25 n male (%) 12 (32%) 10 (36%) 0.32 LVEDV (ml) 168 ± 37 149 ± 31 0.017 LVEDVi (ml/m2) 70.4 ± 12.3 78.8 ± 12.1 0.004 LV Mass (g) 116 ± 31 99 ± 28 0.019 EF (%) 70 ± 8 65 ± 5 0.002 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction

Microvascular and mechanical improvements following bariatric surgery in the obese; mechanistic insights from advanced &amp; automated quantitative perfusion cardiac MRI

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospital Biomedical Research Centre Background In people with obesity, bariatric surgery reduces mortality, heart failure and coronary disease, improving metabolic (blood sugar, lipid profile, inflammation) and cardiovascular (diastolic/systolic function, filling pressure, cardiac remodelling) parameters. Myocardial microvascular function is a candidate causal link of metabolic to structural cardiac abnormalities. Purpose We hypothesised that bariatric surgery could improve myocardial microvascular and mechanical function in both those with and without diabetes. Methods Before and six months after bariatric surgery, 24 subjects with obesity were assessed with haematology, biochemistry and advanced CMR (cines, vasodilator adenosine stress and rest fully-automated quantitative perfusion mapping, tissue-tracking (CVI42, post processing). Results. Mean age was 49± 12 years, 35%(8) were male, 63%(15), had hypertension, 17 (71%) had diabetes. Surgery resulted in decreases in BMI (44 ± 7 to 34 ± 6 kg/m2 p = 0.0001) and HbA1c (57 ± 16 to 42 ± 9mmol/mol p = 0.0001). EF% and absolute LV end-diastolic volumes remained unchanged, but mass regressed and myocardial contraction fraction (ratio of stroke volume and LV volume) increased (see Table). There were also strain improvements (radial 35 ± 8.8 to 37.3 ± 8.7 %p = 0.029) (circumferential -19.8 ± 2.3 vs -20.7 ± 3% p = 0.017), although longitudinal did not improve (-16.3 ± 3.2 to -15.9 ± 3% p = 0.25). Myocardial perfusion significantly improved (stress myocardial blood flow, MBF 2.35 ± 0.71 to 2.80 ± 0.98 ml/g/min p = 0.008; myocardial perfusion reserve MPR 2.47 ± 0.78 to 2.97 ± 0.95 p = 0.005). Improvement in stress MBF and MPR from pre-operative to post-operative was higher in the non-diabetics (n = 7 (29%)) than the diabetics (n = 17 (71%)) (stress MBF: 1.15 ± 1.00 vs 0.16 ± 0.39ml/g/min p = 0.002) MPR: (1.09 ± 0.73 vs 0.25 ± 0.66 p = 0.011). Conclusion At 6 months, bariatric surgery results in beneficial myocardial remodelling and substantial improvements in myocardial microvascular function. These improvements occur most in those without diabetes suggesting that there may be reversible and irreversible components to microvascular dysfunction. Perfusion and strain variables Variable Pre-op (n = 24) Post-op (n = 24) p-value LVEDV (ml) 163 ± 28 161 ± 29 0.64 EF (%) 70 ± 8 70 ± 7 0.78 Stroke volume (ml) 113 ± 19 111 ± 21 0.6 LV Mass (g) 117 ± 25 103 ± 21 0.001 Myocardial contraction fraction 94 ± 14 105 ± 14 0.001 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction Abstract Figure.

Influences on myocardial perfusion in non-obstructive coronary disease: an observational quantitative perfusion mapping study

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by a Clinical Training Research Fellowship (K. Knott) from the British Heart Foundation and directly and indirectly from the Biomedical Research Centre at University College London Hospitals and Barts Heart Centre. Background Cardiovascular magnetic resonance (CMR) with automated inline perfusion mapping permits rapid fully automated non-invasive myocardial blood flow (MBF, ml/g/min). Understanding the microvascular component of MBF would help optimize epicardial coronary artery disease detection and potentially serve as an independent diagnostic / therapeutic target. Purpose To explore MBF influences at stress and rest in patients with unobstructed epicardial coronary arteries. Methods 242 participants (mean age 56.9 years) from 5 European centers with unobstructed epicardial coronary arteries and no myocardial scar underwent adenosine vasodilator perfusion mapping at stress and rest. The factors influencing MBF were determined using univariate and multivariate linear regression analyses. Results Mean rest perfusion was 0.91+/-0.24ml/g/min. Rest perfusion was higher in females (0.97+/-0.22ml/g/min vs 0.83 +/- 0.24ml/g/min) and lower in patients on beta blockers. Mean stress MBF was 2.53+/-0.82ml/g/min. Factors independently associated with reduced stress MBF were increasing age, diabetes, increasing left ventricular mass (LVMi) and the use of beta blockers. The predicted stress MBF can be obtained from the equation MBF = 2.66–0.015(age-60)–0.013(LVMi-57)-0.405(diabetes)–0.365(beta blocker). This means stress MBF falls 10% over 19 years and that diabetes drops the MBF by the equivalent of being 27 years older. These changes are large: for example, a 70-year-old diabetic would have 30% lower stress MBF than a 35 year-old non-diabetic. Conclusions In the absence of obstructive epicardial coronary disease, stress MBF falls with age, diabetes, increased LV mass and beta-blockers. These data may help develop normal reference ranges, input to other modelling (eg CT FFR), and they advance perfusion mapping as a measure of microvascular function. Abstract Figure. Summary of the determinants of perfusion

Quantitative cardiovascular magnetic resonance myocardial perfusion mapping to assess hyperaemic response to adenosine stress.

Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress. Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001). Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response.

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping

ObjectivesThe authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD). BackgroundVA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD. MethodsOne hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps. ResultsIn patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%). ConclusionsVA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Catheter-based Arterial Input Function Determination for Myocardial Perfusion Measurements

The quantification of myocardial perfusion with contrast agent (CA) tracers requires the precise knowledge of the arterial input function (AIF). In this study a method for MR-guided vascular interventions is evaluated that determines the AIF via an active tracking catheter during targeted CA injection. A phantom experiment with a dialysis filter was conducted to measure the AIF using an active catheter and a dynamic image series as reference. To compensate for dilution and coil sensitivity effects, correction methods were developed for the catheter-based AIF determination. From the dynamic MR measurements in the perfusion phantom quantitative perfusion maps were calculated by a deconvolution of the measured CA concentration with the AIF, and additional flow measurements were used to normalize the perfusion map. The signal-time-curves of the measured AIF using the catheter-based and imaging-based methods agree while the absolute values differ by a scaling factor of about 9. After normalization to the surrounding flow, both perfusion techniques are in excellent agreement. Catheter-based AIF measurements are feasible but require an additional normalization which can be determined from a flow measurement. The technique might enable faster perfusion measurements during cardiovascular interventions.

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI.

Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging. Through traditional DSC tracer kinetic modeling, the MR signal change induced by this hypoxic bolus can be used to generate regional perfusion maps of cerebral blood flow, cerebral blood volume, and mean transit time. This gas paradigm and blood-oxygen-level-dependent (BOLD)-MRI were performed concurrently on a cohort of 66 healthy and chronically anemic subjects (age 23.5±9.7, female 64%). Our results showed reasonable global and regional agreement between dDSC and other flow techniques, such as phase contrast and arterial spin labeling. In this proof-of-concept study, we demonstrated the feasibility of using transient hypoxia to generate a contrast bolus that mimics the effect of gadolinium and yields reasonable perfusion estimates. Looking forward, optimization of the hypoxia boluses and measurement of the arterial-input function is necessary to improve the accuracy of dDSC. Additionally, a cross-validation study of dDSC and DSC in brain tumor and ischemic stroke subjects is warranted to evaluate the clinical diagnostic utility of this approach.

Abstract TP141: Can the Human Eye Match a Computer Algorithm in Identifying Hypoperfusion in Asymptomatic Carotid Artery Stenosis?

Background: Perfusion weighted imaging on MRI (MRP) and computerized tomography perfusion (CTP) are increasingly required to manage large vessel disease. Computerized algorithms can quantify perfusion data, but the programs are expensive and not widely used outside acute stroke evaluation. We aimed to determine how well human observers can identify asymmetries in cerebral perfusion images compared with an automated computer algorithm. Methods: Ten clinicians experienced in treating carotid artery disease (4 vascular neurologists, 3 neuroradiologists, 1 vascular surgeon, 1 neurosurgeon, 1 interventional radiologist) were given 28 post-processed, color-coded, axial-slice MRP scans from patients in the Carotid Revascularization Endovascular versus Stenting Trial - Hemodynamics (CREST-H) study. All patients had &gt;70%, unilateral, asymptomatic carotid artery stenosis and had varying degrees of time-to-peak (TTP) delay on the side of stenosis, ranging from 0 to 2 secs, quantified by a semi-automated system that computes quantitative perfusion maps, using deconvolution of tissue and arterial signals (Olea, Cambridge, MA). A minimum volume of 10cc was required for a given TTP delay. Clinicians were asked to determine asymmetry (y/n) and side of occlusion for each case. Number of correct responses that matched the computer output were tallied. Results: We averaged correct responses by the 10 clinicians for cases at each increment of TTP delay; (Figure). At TTP delays ≥1.5 seconds, accuracy was ≥80%. At 1.25 sec accuracy fell to 60%, and at ≤ 1 sec, accuracy was ≤50%. For TTP=0 (no asymmetry), accuracy was 71%. Conclusions: Visual impression of hemodynamic asymmetry among experienced clinicians was reasonably accurate for TTP delays ≥1.5 seconds, but declined with more subtle asymmetries. Depending on the clinical impact of TTP delays (for CREST-H: correlation with cognitive decline), experienced clinicians may perform as well as an automated algorithm.

408 Stress Cardiac Magnetic Resonance With In-Line AI Quantitative Perfusion Mapping; Clinical Experience for Ischaemia and Microvascular Dyfunction

Adenosine Stress Perfusion Cardiac Magnetic Resonance (CMR) is a highly accurate technique for non-invasive assessment of myocardial perfusion, as shown in recent CEMARC, MR-INFORM, SPINS and GADACAD trials. Quantitative perfusion mapping using convoluted neural network artificial intelligence (AI) reconstruction has been proposed to improve accuracy and diagnostic performance. 33 consecutive stress scans CMR clinically referred for evaluation of angina pectoris, performed on a 1.5T Siemens Aera system. Standard sequence was a free-breathing motion corrected FLASH dynamic perfusion after 140mcg/kg adenosine, compared to an investigational work-in-progress myocardial blood flow (MBF) dual bolus technique with automatic arterial input function quantitated in ml/min/g using 16-segment AHA model. 22 scans referred for ischaemia, 11 for microvascular dysfunction. Level-3 expert reader blindly evaluated grey-scale dynamic perfusion imaging, and separately evaluated quantitative perfusion maps. Scans were categorised as ischaemia, microvascular, or normal coronary physiology. Diagnostic confidence was measured on a Likert rating scale from 1 (unconfident) to 3 (very confident). 31/33 scans (94%) had successful perfusion mapping, with 2 excluded due to artefact from arrythmia or failed motion correction. 20/22 scans referred for ischaemia (91%) mapping improved diagnostic confidence (score 2.03 vs 2.88, P<0.001). For all 11 (100%) microvascular dysfunction cases perfusion mapping was diagnostic over standard imaging. Quantitative perfusion mapping improves diagnostic confidence and allows accurate separation of ischaemic vs microvascular causes of angina.

409 WITHDRAWN:Â Stress Perfusion Cardiac Magnetic Resonance With In-Line Artificial Intelligence Quantitative Perfusion Mapping; Clinical Evaluation for Ischaemia and Microvascular Dysfunction

409 WITHDRAWN:Â Stress Perfusion Cardiac Magnetic Resonance With In-Line Artificial Intelligence Quantitative Perfusion Mapping; Clinical Evaluation for Ischaemia and Microvascular Dysfunction

Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy

ObjectiveIn patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We...

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.

P3108Microcirculation injury is involved in anthracycline-induced cardiac toxicity

Abstract Background/Introduction Cardiotoxicity (CT) is a major concern for cancer patients receiving anthracyclines. While the effect of anthracyclines on cardiomyocytes is well established, its impact on myocardial microcirculation has not been characterized. Purpose To evaluate the effect of low and high cumulative doses of doxorubicin (doxo) on anatomical and functional vasculature status evaluated by serial invasive Coronary Flow Reserve (CFR) and Cardiac Magnetic Resonance (CMR)-based quantitative perfusion in a large animal model. Methods Large-white male pigs (n=15, 30 kg) were distributed in 2 doxo regimes: Group 1) high cumulative dose (5 biweekly intracoronary (i.c) injections of 0.45 mg/kg of doxo) followed-up until week 16 (a time when severe left ventricular systolic dysfunction is present) and then sacrificed (N=5); Group 2) low cumulative dose of doxo (3 biweekly i.c. doses) followed-up until week 16 and then sacrificed (N=5)). Group 3) pigs sacrificed at 6 weeks (2 weeks after third doxo dose), N=5. Invasive catheter-based CFR was evaluated after i.c papaverine (0.5 mg/kg) while CMR quantitative rest perfusion maps were obtained after intravenous injection of gadolinium. CFR and CMR were performed before doxo, and at 0, 2, 4, 6 and 16 weeks thereafter. Cardiac vessels were evaluated ex vivo with trichrome staining. Statistical analysis was performed using one-way ANOVA with multiple pairwise comparisons (vs. baseline) and Bonferroni corrected p-value. Results CFR and CMR-quantitative myocardial perfusion were non-significantly reduced after 3 doxo doses despite myocardial vasculature was overtly injured on histology at this timepoint. Animals receiving 5 doxo doses suffered a progressive deterioration of CFR and CMR-perfusion until week 16 (1.41±0.23 vs 3.71±0.94 at baseline [p=0.014] and 65.4±18.2 ml/100g/min vs 154.9±56.3 ml/100g/min at baseline [p=0.046], respectively). At 16 weeks histology revealed extensive microvascular damage with media layer involvement and perivascular fibrosis. Pigs receiving 3 doxo doses showed less pronounced CFR reduction on long-term follow-up (3.13±0.82 vs 3.69±1.57 at baseline [p&gt;0.05] but overt CMR-perfusion reduction (138.3±11.9 vs 197.8±37.1 at baseline [p=0.045]). On histology, damage of vasculature including arterioles was evidenced to a lesser extent than in the high cumulative doxo dose group with mild microvascular disruption and smooth muscle vacuolization. Conclusions Doxorubicin results in a progressive damage of the myocardial microcirculation. Even low cumulative doxo doses (resulting in no overt left ventricular dysfunction) results in vascular damage. The microcirculation status may serve as an early marker of doxorubicin cardiotoxicity.

Automatic in-line quantitative myocardial perfusion mapping: Processing algorithm and implementation.

Quantitative myocardial perfusion mapping has advantages over qualitative assessment, including the ability to detect global flow reduction. However, it is not clinically available and remains a research tool. Building upon the previously described imaging sequence, this study presents algorithm and implementation of an automated solution for inline perfusion flow mapping with step by step performance characterization. Proposed workflow consists of motion correction (MOCO), arterial input function blood detection, intensity to gadolinium concentration conversion, and pixel-wise mapping. A distributed kinetics model, blood-tissue exchange model, is implemented, computing pixel-wise maps of myocardial blood flow (mL/min/g), permeability-surface-area product (mL/min/g), blood volume (mL/g), and interstitial volume (mL/g). Thirty healthy subjects (11 men; 26.4 ± 10.4 years) were recruited and underwent adenosine stress perfusion cardiovascular MR. Mean MOCO quality score was 3.6 ± 0.4 for stress and 3.7 ± 0.4 for rest. Myocardial Dice similarity coefficients after MOCO were significantly improved (P < 1e-6), 0.87 ± 0.05 for stress and 0.86 ± 0.06 for rest. Arterial input function peak gadolinium concentration was 4.4 ± 1.3 mmol/L at stress and 5.2 ± 1.5 mmol/L at rest. Mean myocardial blood flow at stress and rest were 2.82 ± 0.47 mL/min/g and 0.68 ± 0.16 mL/min/g, respectively. The permeability-surface-area product was 1.32 ± 0.26 mL/min/g at stress and 1.09 ± 0.21 mL/min/g at rest (P < 1e-3). Blood volume was 12.0 ± 0.8 mL/100 g at stress and 9.7 ± 1.0 mL/100 g at rest (P < 1e-9), indicating good adenosine vasodilation response. Interstitial volume was 20.8 ± 2.5 mL/100 g at stress and 20.3 ± 2.9 mL/100 g at rest (P = 0.50). An inline perfusion flow mapping workflow is proposed and demonstrated on normal volunteers. Initial evaluation demonstrates this fully automated solution for the respiratory MOCO, arterial input function left ventricle mask detection, and pixel-wise mapping, from free-breathing myocardial perfusion imaging.

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion

Adenosine stress CMR perfusion imaging can quantify absolute perfusion and myocardial perfusion reserve (MPR) in coronary artery disease (CAD) with higher spatial resolution than positron emission tomography, the only clinically available technique for quantitative myocardial perfusion imaging. While porcine models of CAD are excellent for studying perfusion abnormalities in chronic CAD, to date there are a limited number of studies that use quantitative perfusion for evaluation. Therefore, we developed an adenosine stress CMR protocol to evaluate the temporal evolution of perfusion defects in a porcine model of progressive obstructive CAD. 10 Yucatan minipigs underwent placement of an ameroid occluder around the left circumflex artery (LCX) to induce a progressive chronic coronary obstruction. Four animals underwent a hemodynamic dose range experiment to determine the adenosine dose inducing maximal hyperemia. Each animal had a CMR examination, including stress/rest spiral quantitative perfusion imaging at baseline and 1, 3, and 6weeks. Late gadolinium enhancement images determined the presence of myocardial infarction, if any existed. Pixelwise quantitative perfusion maps were generated using Fermi deconvolution. The results were statistically analyzed with a repeated mixed measures model to block for physiological variation between the animals. Five animals developed myocardial infarction by 3weeks, while three developed ischemia without an infarction. The perfusion defects were located in the inferolateral myocardium in the perfusion territory of the LCX. Stress perfusion values were higher in remote segments than both the infarcted and ischemic segments (p<0.01). MPR values were significantly greater in the remote segments than infarcted and ischemic segments (p<0.01). While the MPR decreased in all segments, the MPR recovered by the sixth week in the remote regions. We developed a model of progressive CAD and evaluated the temporal evolution of the development of quantitative perfusion defects. This model will serve as a platform for understanding the development of perfusion abnormalities in chronic occlusive CAD.