Ignite Creation Date:
2024-05-06 @ 5:01 PM
Last Modification Date:
2024-10-26 @ 2:20 PM
Study NCT ID:
NCT05163327
Status:
WITHDRAWN
Last Update Posted:
2023-02-02
First Post:
2021-12-06
Brief Title:
Oxygen-enhanced Magnetic Resonance Imaging OE-MRI of the Heart A Feasibility Study
Sponsor:
Manchester University NHS Foundation Trust
Organization:
Manchester University NHS Foundation Trust
Study Overview
Official Title:
Oxygen-enhanced Magnetic Resonance Imaging OE-MRI of the Heart A Feasibility Study
Status:
WITHDRAWN
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Accumulated evidence including data acquired in parallel studies in other centres and in published literature suggest that the technique was unlikely to produce a signal in the heart
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OE-MRI
Brief Summary:
This exploratory pilot study aims to set up cardiac oxygen enhanced magnetic resonance imaging OE-MRI It will involve 10 healthy volunteers and 10 patients with known coronary artery disease CAD having a MRI scan
If positive this data would be used to power an appropriately sized study assessing the utility of cardiac OE-MRI in CAD and other cardiac pathologies
If positive this data would be used to power an appropriately sized study assessing the utility of cardiac OE-MRI in CAD and other cardiac pathologies
Detailed Description:
Determining the presence and severity of myocardial ischaemia is a key goal in the effective management of coronary artery disease CAD Untreated ischaemia is an important determinant of adverse outcome and the benefits of ischemia-driven revascularization are well recognized1
Anatomic appearances of coronary artery disease are poorly predictive of myocardial ischemia1 2 Therefore concurrent assessment of the functional severity of coronary stenosis is used to guide revascularization3 In the clinical setting a number of imaging methods are available including nuclear techniques echocardiography and cardiovascular magnetic resonance CMR Such modalities assess flow heterogeneity and contractile abnormalities but these serve as surrogates of myocardial ischemia ischemia per se is not measured Furthermore these functional imaging modalities rely on the use of exogenous contrast agents which albeit small carry additional risks and can be contraindicated in certain populations
Blood oxygen level dependent BOLD imaging exploits the inherent paramagnetic properties of haemoglobin4 The transition from diamagnetic oxyhaemoglobin to paramagnetic deoxyhaemoglobin induces magnetic susceptibility differences resulting in a change in magnetic resonance signal intensity and thereby generating oxygen dependent contrast Thus BOLD imaging provides insight into myocardial tissue oxygenation Since hypoxia is the initiator of the ischaemic cascade assessment of regional myocardial oxygenation with BOLD imaging has been hypothesised to reflect more directly the imbalance between oxygen supply and demand and be sensitive for detecting CAD Indeed initial evaluation of BOLD imaging for detecting CAD has produced promising results5-7 Furthermore BOLD has provided pathological insight into other myocardial pathologies Myocardial perfusion blood flow can be dissociated from oxygenation ie hypoperfusion is not necessarily commensurate with tissue hypoxia For example myocardial oxygen demand may be down-regulated in hibernating myocardium and may be upregulated in hypertrophic cardiomyopathy HCM due to the increased cost of energy metabolism In HCM mutation carriers without left ventricular hypertrophy Karamitsos et al demonstrated normal myocardial perfusion reserve but abnormal myocardial oxygenation during stress possibly explained by the fact that sarcomere gene mutations increase the energy cost of contraction before the onset of hypertrophy8
However BOLD imaging is associated with a number of disadvantages First since the BOLD signal reflects deoxyhaemoglobin which is confined to blood vessels it doesnt truly reflect tissue oxygen status9 Second the BOLD signal is also dependent on vessel geometry changes in blood flow and blood volume which thus can confound the signal9 Finally the CMR techniques used to measure the BOLD signal T2 of T2 are not quantitative since a change in T2 or T2 cannot be related to a change in the partial pressure of oxygen PO2 Instead semi-quantitative measurements are made using signal intensity and are assumed to reflect oxygenation
Oxygen enhanced magnetic resonance imaging OE-MRI potentially overcomes these limitations Oxygen itself has paramagnetic properties it increases the proton longitudinal relaxation rate R1 of water containing dissolved oxygen10 The measured change in R1 1T1 where T1 relaxation time is an inherent magnetic property of all tissues induced by breathing oxygen is directly proportional to the change in PO2 In OE-MRI the change in R1 on breathing elevated concentrations of oxygen is measured The benefits of OE-MRI over BOLD are therefore that it is sensitive to tissue oxygenation it is not dependent on changes in blood flow and volume and it is truly quantitative since the change in R1 is directly proportional to the change in PO2 Thus it potentially offers a quantitative measure of myocardial oxygenation OE-MRI has been used to assess lung tissue oxygenation11 solid tumour oxygenation12 and to assess placental oxygenation in pregnant women13 on conventional clinical MRI scanners with very encouraging results
OE-MRI has not been applied in the heart We hypothesise that OE-MRI will allow non-invasive non-ionising and quantitative assessment of myocardial tissue oxygenation that is free from exogenous contrast agent If this is the case OE-MRI will offer enormous potential in terms of the diagnosis and management of CAD and in terms of providing pathophysiological insight into cardiac disease
Anatomic appearances of coronary artery disease are poorly predictive of myocardial ischemia1 2 Therefore concurrent assessment of the functional severity of coronary stenosis is used to guide revascularization3 In the clinical setting a number of imaging methods are available including nuclear techniques echocardiography and cardiovascular magnetic resonance CMR Such modalities assess flow heterogeneity and contractile abnormalities but these serve as surrogates of myocardial ischemia ischemia per se is not measured Furthermore these functional imaging modalities rely on the use of exogenous contrast agents which albeit small carry additional risks and can be contraindicated in certain populations
Blood oxygen level dependent BOLD imaging exploits the inherent paramagnetic properties of haemoglobin4 The transition from diamagnetic oxyhaemoglobin to paramagnetic deoxyhaemoglobin induces magnetic susceptibility differences resulting in a change in magnetic resonance signal intensity and thereby generating oxygen dependent contrast Thus BOLD imaging provides insight into myocardial tissue oxygenation Since hypoxia is the initiator of the ischaemic cascade assessment of regional myocardial oxygenation with BOLD imaging has been hypothesised to reflect more directly the imbalance between oxygen supply and demand and be sensitive for detecting CAD Indeed initial evaluation of BOLD imaging for detecting CAD has produced promising results5-7 Furthermore BOLD has provided pathological insight into other myocardial pathologies Myocardial perfusion blood flow can be dissociated from oxygenation ie hypoperfusion is not necessarily commensurate with tissue hypoxia For example myocardial oxygen demand may be down-regulated in hibernating myocardium and may be upregulated in hypertrophic cardiomyopathy HCM due to the increased cost of energy metabolism In HCM mutation carriers without left ventricular hypertrophy Karamitsos et al demonstrated normal myocardial perfusion reserve but abnormal myocardial oxygenation during stress possibly explained by the fact that sarcomere gene mutations increase the energy cost of contraction before the onset of hypertrophy8
However BOLD imaging is associated with a number of disadvantages First since the BOLD signal reflects deoxyhaemoglobin which is confined to blood vessels it doesnt truly reflect tissue oxygen status9 Second the BOLD signal is also dependent on vessel geometry changes in blood flow and blood volume which thus can confound the signal9 Finally the CMR techniques used to measure the BOLD signal T2 of T2 are not quantitative since a change in T2 or T2 cannot be related to a change in the partial pressure of oxygen PO2 Instead semi-quantitative measurements are made using signal intensity and are assumed to reflect oxygenation
Oxygen enhanced magnetic resonance imaging OE-MRI potentially overcomes these limitations Oxygen itself has paramagnetic properties it increases the proton longitudinal relaxation rate R1 of water containing dissolved oxygen10 The measured change in R1 1T1 where T1 relaxation time is an inherent magnetic property of all tissues induced by breathing oxygen is directly proportional to the change in PO2 In OE-MRI the change in R1 on breathing elevated concentrations of oxygen is measured The benefits of OE-MRI over BOLD are therefore that it is sensitive to tissue oxygenation it is not dependent on changes in blood flow and volume and it is truly quantitative since the change in R1 is directly proportional to the change in PO2 Thus it potentially offers a quantitative measure of myocardial oxygenation OE-MRI has been used to assess lung tissue oxygenation11 solid tumour oxygenation12 and to assess placental oxygenation in pregnant women13 on conventional clinical MRI scanners with very encouraging results
OE-MRI has not been applied in the heart We hypothesise that OE-MRI will allow non-invasive non-ionising and quantitative assessment of myocardial tissue oxygenation that is free from exogenous contrast agent If this is the case OE-MRI will offer enormous potential in terms of the diagnosis and management of CAD and in terms of providing pathophysiological insight into cardiac disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None