Changes In Myocardial Oxygenation Research Articles

Coronary vascular function in females with history of hypertensive disorders of pregnancy an oxygenation-sensitive cardiovascular magnetic resonance imaging study

Abstract Background Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, have been associated with increased risk for cardiovascular disease decades after HDP pregnancy. HDP is thought to unmask pre-existing cardiovascular risk in the mother; and in addition HDP triggers a cascade of inflammatory and oxidative stress which leads to vascular endothelial dysfunction and abnormalities in cardiac structure and function evident early post-partum that may persist sub-clinically. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) is an emerging approach that can identify dynamic changes of myocardial oxygenation as a marker for coronary vascular function. The objective of this study was to assess coronary vascular function in females with history of HDP using OS-CMR. Methods We analyzed data from two short axis OS-CMR slices in 20 females with history of HDP, including gestational hypertension, preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) and 20 healthy controls with history of normal pregnancy acquired on a 1.5T MRI scanner. Images were analyzed using a prototype tissue oxygenation module. The images were normalized for signal intensity to both ventricular blood pools. We used both traditional statistics and feature selection machine learning algorithms to select for predictive biomarkers in the dataset. Finally, we used a random forest classifier model for disease classification. We report area under the receiver operating curve (AUROC) as a metric for diagnostic accuracy. Results Global breathing-induced myocardial oxygenation reserve (B-MORE) of the mid left ventricular slice was significantly reduced in HDP females (-1.6 ± 14.8) when compared to healthy controls (11.3 ± 17.2, p=0.03), when normalized to ventricular blood pools (Figure 1A). Our feature selection algorithm selected the signal intensity during end-systole normalized to the series as the most predictive biomarker. Our model, which integrated data from >3,300 discrete data points per participant, correctly differentiated healthy controls from women with HDP history with a 90% ± 3% AUROC accuracy, indicating high sensitivity and specificity (Figure 1B). Conclusion Compared to healthy controls, females with history of HDP have abnormal coronary vascular function, as shown by reduced myocardial oxygenation on OS-CMR. Combining advanced machine learning approaches can further enhance the potential application of OS-CMR to risk stratify females with adverse pregnancy outcomes susceptible to future cardiovascular disease.

Dynamic changes in myocardial oxygenation and function during induction of general anaesthesia: Quantification by cardiovascular magnetic resonance imaging

Dynamic changes in myocardial oxygenation and function during induction of general anaesthesia: Quantification by cardiovascular magnetic resonance imaging

VALIDATING NOVEL FREE-BREATHING CARDIOVASCULAR MAGNETIC RESONANCE SEQUENCES FOR FUTURE APPLICATIONS OF PERI-OPERATIVE IMAGING OF INDUCIBLE MYOCARDIAL DEOXYGENATION

<h3>Background</h3> Perioperative myocardial ischemia is associated with increased morbidity and mortality. General anesthesia (GA) bears many possible triggers for myocardial ischemia including acute blood gas changes. While cardiovascular magnetic resonance (CMR) is not feasible in an everyday intra-operative setting, its ability to measure myocardial oxygenation using oxygen-sensitive (OS) imaging provides a novel possibility to quantify tissue ischemia during the induction of GA in a research setting. However, OS-CMR is acquired during a breath-hold to reduce chest motion and requires up to 10s per image, and hence is not ideal for continuous monitoring. Thus, we optimized two free breathing OS-CMR sequence variants that acquire images every heartbeat to measure rapid changes in myocardial oxygenation. We aimed to compare these new sequences in an awake healthy control population performing voluntary hyperventilation and apnea. The intent of this analysis is to develop and validate this new CMR sequence for future studies implementing OS-CMR to measure myocardial oxygenation during GA. <h3>Methods</h3> Twenty awake healthy participants underwent a CMR study and performed two breathing protocols. First a maneuver representing anesthesia pre-induction protocols was performed with paced breathing at 15bpm for 150s followed by 5 deep breaths and then apnea. Controls were then asked to perform a rapid paced maneuver consisting of 60s of deep hyperventilation at 30bpm for 60s, followed by a second apnea phase. During the procedure images were acquired with the original breath-hold (BH) OS-CMR sequence, the new free-breathing single shot (SS-FB) and real-time (RT-FB) sequences. The first is a single-shot variant that only acquires one image in diastole at a high resolution of 1.5mm2. The second is a real-time variant, that acquires 20 frames per second thus providing functional information throughout the cardiac cycle as well, but at a spatial resolution of 3mm2. Myocardial oxygenation was statistically compared at baseline, post hyperventilation which is a vasoconstricting stimulus, and at the 30s timepoint in apnea that is known to induce vasodilation. <h3>Results</h3> For the first breathing pacing protocol representing GA induction, hyperventilation significantly reduced myocardial oxygenation with all three sequences (SS-FB: -12.1±10.6%, p<0.001, RT-FB: -8.0 ±4.0% p<0.001, BH: -4.2±3.7% p<0.001) and apnea resulted in a rise in myocardial oxygenation (SS-FB: 6.2±7.3% p=0.002, RT-FB: 11.8±4.1% p<0.001, BH: 6.9±5.7% p<0.001). With the rapid pacing maneuver similar results were observed with hyperventilation (SS-FB: -4.4±8.2% p=0.047, RT-FB: -7.0±1.8% p<0.001, BH: -4.3±6.2% p=0.008) and apnea (SS-FB: 9.2±6.5% p=<0.001, RT-FB: 9.1±2.1% p<0.001, BH: 4.5±5.0% p=0.001). The new SS-FB and RT-FB sequences were not inferior to the known gold standard BH sequence for any stage. <h3>Conclusion</h3> In awake controls, alterations in myocardial oxygenation through hyperventilation and apnea can be observed with the novel free-breathing OS-CMR sequences. It is now warranted to implement these new techniques in future studies investigating peri-operative imaging of myocardial ischemia.

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction.

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents. OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4 min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided. As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

Oxygenation-sensitive cardiac magnetic resonance imaging

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is an evolving cardiac imaging technique offering new perspectives to understand, predict, and diagnose cardiac pathologies. To provide an overview of the basic principles of OS-CMR, the current diagnostic applications and how it may aid in future diagnostic challenges. Description, analysis, and interpretation of the current literature on basic research and applicational studies in both humans and animals assessing OS-CMR. OS-CMR is based on the paramagnetic properties of deoxygenated hemoglobin, which is visualized by aT2*-sensitive sequence. The measured signal correlates with the oxygenation of the myocardium and can analyze vascular function during pharmacological vasodilation or vasoactive breathing exercises (hyperventilation, apnea). The herewith triggered changes in myocardial oxygenation and oxygenation reserve can be used to identify relevant stenoses in coronary artery disease. Other areas of application involve myocardial hypertrophy, microvascular dysfunction, and pulmonary hypertension. A broad number of applications for the clinical use of OS-CMR exist so far, especially in combination with breathing exercises. OS-CMR can be conducted medication- and needle-free. Limitations involve the current lack of clinically approved, automated evaluation tools and the unavailability of vendor- and site-independent normal values.

Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome.

IntroductionIn patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction.MethodsA group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain.ResultsIn healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (−5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone.ConclusionIn myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.

The Potential of Oxygenation-Sensitive CMR in Heart Failure.

Cardiac magnetic resonance imaging (CMR) use in the context of heart failure (HF) has increased over the last decade as it is able to provide detailed, quantitative information on function, morphology, and myocardial tissue composition. Furthermore, oxygenation-sensitive CMR (OS-CMR) has emerged as a CMR imaging method capable of monitoring changes of myocardial oxygenation without the use of exogenous contrast agents. The contributions of OS-CMR to the investigation of patients with HF includes not only a fully quantitative assessment of cardiac morphology, function, and tissue characteristics, but also high-resolution information on both endothelium-dependent and endothelium-independent vascular function as assessed through changes of myocardial oxygenation. In patients with heart failure, OS-CMR can provide deep phenotyping on the status and important associated pathophysiology as a one-stop, needle-free diagnostic imaging test.

Noninvasive oxygenation assessment after acute myocardial infarction with breathing maneuvers-induced oxygenation-sensitive magnetic resonance imaging.

The safety profiles when performing stress oxygenation-sensitive magnetic resonance imaging (OS-MRI) have raised concerns in clinical practice. Adenosine infusion can cause side effects such as chest pain, dyspnea, arrhythmia, and even cardiac death. The aim of this study was to investigate the feasibility of breathing maneuvers-induced OS-MRI in acute myocardial infarction (MI). This was a prospective study, which included 14 healthy rabbits and nine MI rabbit models. This study used 3T MRI/modified Look-Locker inversion recovery sequence for native T1 mapping, balanced steady-state free precession sequence for OS imaging, and phase-sensitive inversion recovery sequence for late gadolinium enhancement. The changes in myocardial oxygenation (ΔSI) were assessed under two breathing maneuvers protocols in healthy rabbits: a series of extended breath-holding (BH), and a combined maneuver of hyperventilation followed by the extended BH (HVBH). Subsequently, OS-MRI with HVBH in acute MI rabbits was performed, and the ΔSI was compared with that of adenosine stress protocol. Student's t-test, Wilcoxon rank test, and Friedman test were used to compare ΔSI in different subgroups. Pearson and Spearman correlation was used to obtain the association of ΔSI between breathing maneuvers and adenosine stress. Bland-Altman analysis was used to assess the bias of ΔSI between HVBH and adenosine stress. In healthy rabbits, BH maneuvers from 30 to 50 s induced significant increase in SI compared with the baseline (all p < 0.05). By contrast, hyperventilation for 60 s followed by 10 s-BH (HVBH 10 s) exhibited a comparable ΔSI to that of stress test (p=0.07). In acute MI rabbits, HVBH 10 s-induced ΔSIs among infarcted, salvaged, and the remote myocardial area were no less effectiveness than adenosine stress when performing OS-MRI (r=0.84; p < 0.05). Combined breathing maneuvers with OS-MRI have the potential to be used as a nonpharmacological alternative for assessing myocardial oxygenation in patients with acute MI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging.

Myocardial oxygenation-the ability of blood vessels to supply the heart muscle (myocardium) with oxygen-is a critical determinant of cardiac function. Impairment of myocardial oxygenation is a defining feature of ischemic heart disease (IHD), which is caused by pathological conditions that affect the blood vessels supplying oxygen to the heart muscle. Detecting altered myocardial oxygenation can help guide interventions and prevent acute life-threatening events such as heart attacks (myocardial infarction); however, current diagnosis of IHD relies on surrogate metrics and exogenous contrast agents for which many patients are contraindicated. An oxygenation-sensitive cardiac magnetic resonance imaging (CMR) approach used previously to demonstrate that CMR signals can be sensitized to changes in myocardial oxygenation showed limited ability to detect small changes in signals in the heart because of physiologic and imaging noise during data acquisition. Here, we demonstrate a CMR-based approach termed cfMRI [cardiac functional magnetic resonance imaging (MRI)] that detects myocardial oxygenation. cfMRI uses carbon dioxide for repeat interrogation of the functional capacity of the heart's blood vessels via a fast MRI approach suitable for clinical adoption without limitations of key confounders (cardiac/respiratory motion and heart rate changes). This method integrates multiple whole-heart images within a computational framework to reduce noise, producing confidence maps of alterations in myocardial oxygenation. cfMRI permits noninvasive monitoring of myocardial oxygenation without requiring ionizing radiation, contrast agents, or needles. This has the potential to broaden our ability to noninvasively identify IHD and a diverse spectrum of heart diseases related to myocardial ischemia.

Cardiovascular risk is associated with a transmural gradient of myocardial oxygenation during adenosine infusion.

In patients with coronary artery disease (CAD), a transmural gradient of myocardial perfusion has been repeatedly observed, with the subendocardial layer showing more pronounced perfusion deficits. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) allows for monitoring transmural changes of myocardial oxygenation in vivo. We hypothesized that OS-CMR could help identify a transmural oxygenation gradient as a disease marker in patients at risk for CAD. We assessed 34 patients with known CAD and 28 subjects with coronary risk factors but no evidence of significant CAD. Results were compared with 11 healthy volunteers. OS-CMR was performed at 1.5 T, applying a T2*-weighted cine steady state free precession sequence at baseline and during infusion of adenosine. A reader blinded to patient data quantified the relative change of myocardial oxygenation in OS-CMR, defined by the change of signal intensity (ΔSI%) between baseline and during adenosine infusion in the entire myocardium, the subepicardial layer, and the subendocardial layer. SI changes were homogenous throughout the myocardium in healthy subjects, whereas both, patients with risk factors only and patients with CAD, had a significantly smaller ΔSI% in the subendocardial layer than in the subendocardial layer. Both patient groups had an overall decreased ΔSI% across all layers when compared with healthy subjects (P < 0.05). Even in the absence of overt CAD, cardiovascular risk factors are associated with a transmural gradient of the myocardial oxygenation response to adenosine as assessed by OS-CMR. An inducible transmural oxygenation gradient may serve as a non-invasive marker for cardiovascular risk.

Feasibility of cardiovascular magnetic resonance to detect oxygenation deficits in patients with multi-vessel coronary artery disease triggered by breathing maneuvers

BackgroundHyperventilation with a subsequent breath-hold has been successfully used as a non-pharmacological vasoactive stimulus to induce changes in myocardial oxygenation. The purpose of this pilot study was to assess if this maneuver is feasible in patients with multi-vessel coronary artery disease (CAD), and if it is effective at detecting coronary artery stenosis > 50% determined by quantitative coronary angiography (QCA).MethodsTwenty-six patients with coronary artery stenosis (QCA > 50% diameter stenosis) underwent a contrast-free cardiovascular magnetic resonance (CMR) exam in the time interval between their primary coronary angiography and a subsequent percutaneous coronary intervention (PCI, n = 24) or coronary artery bypass (CABG, n = 2) revascularization procedure. The CMR exam involved standard function imaging, myocardial strain analysis, T2 mapping, native T1 mapping and oxygenation-sensitive CMR (OS-CMR) imaging. During OS-CMR, participants performed a paced hyperventilation for 60s followed by a breath-hold to induce a vasoactive stimulus. Ten healthy subjects underwent the CMR protocol as the control group.ResultsAll CAD patients completed the breathing maneuvers with an average breath-hold duration of 48 ± 23 s following hyperventilation and without any complications or adverse effects. In comparison to healthy subjects, CAD patients had a significantly attenuated global myocardial oxygenation response to both hyperventilation (− 9.6 ± 6.8% vs. -3.1 ± 6.5%, p = 0.012) and apnea (11.3 ± 6.1% vs. 2.1 ± 4.4%, p < 0.001). The breath-hold maneuver unmasked regional oxygenation differences in territories subtended by a stenotic coronary artery in comparison to remote territory within the same patient (0.5 ± 3.8 vs. 3.8 ± 5.3%, p = 0.011).ConclusionBreathing maneuvers in conjunction with OS-CMR are clinically feasible in CAD patients. Furthermore, OS-CMR demonstrates myocardial oxygenation abnormalities in regional myocardium related to CAD without the use of pharmacologic vasodilators or contrast agents. A larger trial appears warranted for a better understanding of its diagnostic utility.Trial registrationClinical Trials Identifier: NCT02233634, registered 8 September 2014.

Impact of hyperventilation and apnea on myocardial oxygenation in patients with obstructive sleep apnea – An oxygenation-sensitive CMR study

BackgroundOxygenation-sensitive cardiovascular magnetic resonance imaging (OS-CMR) is an emerging technique that can monitor changes in myocardial oxygenation in vivo. Obstructive sleep apnea syndrome (OSAS) is associated with endothelial and microcirculatory dysfunction and increased cardiovascular morbidity and mortality. Little is known about myocardial responses to apnea in patients with OSAS.We hypothesized that the coronary vascular response to hyperventilation and long breath-hold is diminished in patients with OSAS when compared to healthy volunteers. MethodsTwenty-nine OSAS patients and 36 healthy volunteers were prospectively enrolled. All CMR scans were performed on a clinical 3T system. Participants performed a breathing maneuver with 60s of hyperventilation followed by a maximal breath-hold. During the breath-hold, OS-CMR images were continuously acquired and signal intensity changes were measured by a blinded reader. ResultsPatients with OSAS were older than healthy volunteers (p<0.01) and presented more co-morbidities; 66% were currently treated with nocturnal positive airway pressure. Compared to healthy participants, the expected increase of myocardial oxygenation during the first 15s of the breath-hold was significantly lower in patients with OSAS (2.6±8.3% vs. 6.7±5.6%; p<0.05), and remained reduced at all time points during the breath-hold. Importantly this result was mainly driven by patients under continuous positive airway pressure (CPAP), suggesting that CPAP might have a greater impact on increase of myocardial oxygenation rather than OSAS itself. ConclusionsThe myocardial vascular response to combined breathing maneuvers of hyperventilation followed by voluntary apnea is blunted in patients with obstructive sleep apnea. Clinical studies should now further define the clinical role of oxygenation-sensitive CMR in patients with respiratory disorders.

No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure.

Background—Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation.Methods and Results—Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4–6 minutes IV adenosine, 140 μg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using 31P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%; P=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10; P=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (P=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (R=0.06; P=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06; P=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08; P=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%; P=0.46; Δ 2±1%).Conclusions—Our results demonstrate dissociation between microvascular dysfunction and oxygenation in DCM, suggesting that the impairment of perfusion is not sufficient to cause deoxygenation during stress. Cardiac energetics are unaffected by oxygen supplementation, indicating the absence of relevant myocardial hypoxia at rest. Our study suggests that novel treatments for nonischemic heart failure should focus on efforts to directly target cardiomyocyte function and metabolism rather than oxygen delivery and microvascular function.

MYOCARDIAL PERFUSION COMPENSATES FOR INCREASED CARDIAC WORKLOAD DURING PHENYLEPHRINE, MAINTAINING OXYGENATION

s S75 phenylephrine (16-660mg/min, a1-agonist). By deep anaesthesia and Urapidil (a1-blockade), lower blood pressures were achieved. In a 3T MRI scanner, OS-images were acquired at 10-15mmHg increments in a mid left ventricular short axis slice and changes in signal intensity (SI) and myocardial flow response were expressed as %-change 70mmHg baseline. At each level, coronary blood flow was obtained and changes in O2er (D) were calculated (1⁄4100*[CaO2-CvO2/CaO2]), comparing the changes to the oxygenation response. RESULTS: With increasing MAP there was a strong correlation to the LAD blood flow response (red) and a moderate correlation to changes in myocardial oxygenation represented by signal intensity (blue). There was a weak correlation between myocardial OS-SI and flow response changes. Interestingly, there was a weak negative correlation between MAP and O2er changes (green), indicating that during the MAP increase there was a luxury perfusion that exceeded the myocardial oxygen demand, allowing OS-SI to increase, while O2er dropped. This was confirmed by the negative correlation of O2er with OS-SI and flow response. RPP showed the same trend as MAP (table) to flow and O2er, yet no relationship was found to SI. CONCLUSION: a1-mediated blood pressure changes induced by phenylephrine result in a luxury perfusion paralleled by an increase in myocardial oxygenation, despite increased myocardial workload. Oxygenation-sensitive cardiovascular magnetic resonance is a suitable tool to monitor the effects of vasopressors on myocardial oxygenation. Research in Anaesthesiology and Intensive Care Medicine, Inselspital Bern University Hospital 147 SURGICAL APPLICATION OF A NOVEL BIOMATERIAL ATTENUATES POST-MI REMODELING AND HEART FAILURE: IMPACT OF INTERVENTION TIMING RELATIVE TO INFARCT STAGE ON FUNCTIONAL RECOVERY HE Mewhort, JD Turnbull, G Teng, DD Belke, DA Svystonyuk, DG Guzzardi, HJ Duff, PW Fedak

Myocardial blood flow reflects myocardial oxygenation in healthy swine

Myocardial auto-regulation secures a near constant myocardial blood flow through a wide range of systemic blood pressures. However, it is not clear if coronary auto-regulation can maintain myocardial oxygenation in the face of increasing peripheral resistance and cardiac workload. Oxygenation-sensitive (OS) cardiovascular magnetic resonance (CMR) can detect changes in myocardial oxygenation. The aim of this study was to assess myocardial oxygenation during and beyond the myocardial auto-regulation range. Five anaesthetized swine underwent a left-sided thoracotomy to install a flow probe around the proximal left descending coronary artery (LAD). Blood pressure was manipulated from mean arterial pressures (MAP) of 40-180mmHg by continuous administration of Phenylephrine (16-500µg/min). Lower blood pressures were achieved by deep anaesthesia and additional α1-blockade with Urapidil. In a 3T MRI scanner, OS-images were acquired at 10-15mmHg increments in a mid left ventricular short axis slice and expressed as %change in signal intensity (SI) from a defined 70mmHg baseline. Blood pressure and coronary artery blood flow were continuously recorded. The auto-regulation range in these animals was visible with MAP between 40-110mmHg (grey). OS-SI changes (black) showed a good correlation to LAD blood flow (R=0.5, p<0.01), a strong correlation with MAP (R=0.6, p=0.001) and a weak correlation to the rate pressure product (R=0.3, p<0.05). Myocardial oxygenation parallels LAD blood flow in healthy swine. There is no evidence for a compromise in myocardial oxygenation with increased cardiac afterload at higher blood pressures beyond the auto-regulation range

Synthetic Generation of Myocardial Blood–Oxygen-Level-Dependent MRI Time Series Via Structural Sparse Decomposition Modeling

This paper aims to identify approaches that generate appropriate synthetic data (computer generated) for cardiac phase-resolved blood-oxygen-level-dependent (CP-BOLD) MRI. CP-BOLD MRI is a new contrast agent- and stress-free approach for examining changes in myocardial oxygenation in response to coronary artery disease. However, since signal intensity changes are subtle, rapid visualization is not possible with the naked eye. Quantifying and visualizing the extent of disease relies on myocardial segmentation and registration to isolate the myocardium and establish temporal correspondences and ischemia detection algorithms to identify temporal differences in BOLD signal intensity patterns. If transmurality of the defect is of interest pixel-level analysis is necessary and thus a higher precision in registration is required. Such precision is currently not available affecting the design and performance of the ischemia detection algorithms. In this work, to enable algorithmic developments of ischemia detection irrespective to registration accuracy, we propose an approach that generates synthetic pixel-level myocardial time series. We do this by 1) modeling the temporal changes in BOLD signal intensity based on sparse multi-component dictionary learning, whereby segmentally derived myocardial time series are extracted from canine experimental data to learn the model; and 2) demonstrating the resemblance between real and synthetic time series for validation purposes. We envision that the proposed approach has the capacity to accelerate development of tools for ischemia detection while markedly reducing experimental costs so that cardiac BOLD MRI can be rapidly translated into the clinical arena for the noninvasive assessment of ischemic heart disease.

Structured dictionaries for ischemia estimation in cardiac BOLD MRI at rest.

Cardiac Phase-resolved Blood-Oxygen-Level-Dependent (CP-BOLD) MRI examines changes in myocardial oxygenation in response to ischemia without contrast and stress agents. Since signal intensity changes are subtle, quantitative approaches are necessary to examine variations in myocardial BOLD signals and identify ischemic myocardial territories. Here, using data from animal studies, we extract myocardial time series (BOLD signal as a function of cardiac phase) and explore such variations using a structured dictionary-learning framework, considering shift-invariant learning and spatial priors. We use it: to learn a model of baseline (absence of disease) myocardial time series; and in datasets where disease is assumed, to obtain a spatial map of ischemia presence, identifying myocardial time series from ischemic territories in an unsupervised fashion, by exploiting structural properties, or the lack thereof, in the data. By providing new visualization and quantification approaches, we hope to accelerate the clinical translation of cardiac BOLD MRI for noninvasive ischemia assessment.

Myocardial oxygenation is maintained during hypoxia when combined with apnea - a cardiovascular MR study

Oxygenation-sensitive (OS) cardiovascular magnetic resonance (CMR) is used to noninvasively measure myocardial oxygenation changes during pharmacologic vasodilation. The use of breathing maneuvers with OS CMR for diagnostic purposes has been recently proposed based on the vasodilatory effect of Co2, which can be enhanced by the additive effect of mild hypoxia. This study seeks to investigate this synergistic concept on coronary arteriolar resistance with OS CMR. In nine anesthetized swine, normoxemic and mild hypoxemic arterial partial pressure of oxygen (Pao2) levels (100 and 80 mmHg) were targeted with three arterial partial pressure of carbon dioxide (Paco2) levels of 30, 40, and 50 mmHg. During a 60-sec apnea from the set baselines, OS T2*-weighted gradient echo steady-state free precession (SSFP) cine series were obtained in a clinical 1.5T magnetic resonance imaging (MRI) system. Arterial blood gases were acquired prior to and after apnea. Changes in global myocardial signal intensity (SI) were measured. Although a greater drop in arterial oxygen saturation (SaO2) was observed in the hypoxemic baselines, myocardial SI increased or was maintained during apnea in all levels (n = 6). An observed decrease in left ventricular blood pool SI was correlated with the drop in SaO2. Corrected for the arterial desaturation, the calculated SI increase attributable to the increase in myocardial blood flow was greater in the hypoxemic levels. Both the changes in Paco2 and Pao2 were correlated with myocardial SI changes at normoxemia, yet not at hypoxemic levels. Using OS CMR, we found evidence that myocardial oxygenation is preserved during hypoxia when combined with Co2-increasing maneuvers, indicating synergistic effects of hypoxemia and hypercapnia on myocardial blood flow.

Alterations of Myocardial Oxygenation During Voluntary Apnea in Patients With Obstructive Sleep Apnea Syndrome: A Study Using Oxygenation-Sensitive Cardiovascular Mr

Patients with obstructive sleep apnea syndrome (SAS) suffer from repeated episodes of hypoxemia and it is however unknown how this may affect regulation of myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) detects changes of myocardial oxygenation by associated changes of signal intensity (SI). We have recently demonstrated that apnea induces a vasodilatory response in the myocardium with an increase of myocardial oxygenation after the breath-hold. In this study we assessed the variation of SI change throughout the breath-hold.

Is There a Different Response to Hypoxia in Patients Wit Sleep Apnea Syndrome Compared to Healthy Volunteers Assessed With Oxygenation Sensitive CMR?

In patients with obstructive sleep apnea syndrome (SAS), repetitive brief episodes of ischemia occur and may lead to a phenomenon similar to ischemic preconditioning, protecting the heart from ischemia. T2* weighted CMR is an emerging technique, providing oxygenation-sensitive images. It has been shown that in healthy volunteers, apnea leads to coronary vasodilation with a net increase of myocardial oxygenation. We hypothesized that myocardial oxygenation changes during apnea in patients with SAS are different from healthy volunteers.