Quantitative Analysis of Cardiac Muscle Perfusion

Myocardial Ischemia

Fully quantitative stress perfusion, CMR

Full quantitative perfusion of the myocardial wall using MRI is a difficult method for several reasons. First the perfusion algorithm is mostly only relatively available, usually available algorithms /e.g. ISP/ shows not precise results according to our measurements, secondly based on signal physics and nature of MRI scans is not easy to get absolute numbers and specific new algorithms must be developed and tested. Such a tool is not only needed for some special cohort of patients, like 3-vessel disease, coronary artery disease or diffuse coronary artery involvement in coronary vasculopathy in patients after heart transplantation. Fully quantitative perfusion analysis is highly needed for nearly all cardiac patients to better characterise the health and status of the myocardium.

The aim of the study is to optimise the scanning and evaluation of stress perfusion with respect to the quantification of measurement results. Cardiovascular diseases remain the leading cause of death among patients in developed countries. One of the most significant conditions within this group is ischemic heart disease (IHD), a state in which restricted blood flow through the coronary arteries results in myocardial ischemia. At present, emphasis is placed on non-invasive diagnostic approaches to detect this condition. One such method is stress myocardial perfusion imaging. Currently, this examination using magnetic resonance imaging (MRI) is mainly limited to qualitative assessment, in which the examiner evaluates perfusion defects based on a subjective visual assessment of myocardial blood flow, or semi-quantitative assessment, in which blood flow in individual myocardial segments is evaluated from the slope of signal-time curves. In this study, perfusion defects in individual segments will be assessed using quantitative analysis, i.e., direct calculation of blood flow in millilitres per gram of myocardial tissue, and the results will be compared with the aforementioned qualitative and semi-quantitative methods currently used in clinical practice. In contrast, quantitative assessment of stress perfusion offers significant advantages, particularly the ability to provide an objective evaluation independent of the interpreting physician, improved diagnostic accuracy, and, importantly, the potential to diagnose patients with diffuse perfusion impairment across all vascular territories - for example, in those with three-vessel disease. However, fully quantified myocardial perfusion assessment is technically demanding and faces several limitations. The examination will be performed using a CE-marked Philips MRI system, with various frequencies and acquisition modules being evaluated. The following quantitative CMR perfusion parameters will be analyzed: Parameter Description Myocardial Blood Flow (MBF) Blood flow through the myocardium, expressed in ml/min/g of tissue. Measured for individual myocardial segments. Myocardial Perfusion Reserve (MPR) Ratio of MBF during stress to MBF at rest: MPR = MBF\_stress / MBF\_rest, indicating the perfusion reserve. Arterial Input Function (AIF) Contrast concentration in the left ventricle or aorta, serving as the reference input signal for MBF calculation. Time to Peak (TTP) Time required for the myocardial signal to reach its maximum after bolus administration (indicator of delayed flow). Upslope Slope of the rising phase of the perfusion curve - a relative measure of perfusion (often used in semi-quantitative analysis). Peak Signal Intensity (PSI) Maximum signal value following contrast arrival (less commonly used as a standalone parameter). Myocardial perfusion will be conducted according to the standard ESC perfusion protocol, using Gadolinium-based contrast agent (Gadovist) at a dose of 0.1 mmol/kg (0.1 ml/kg) administered at 3-5 ml/s, followed by 20 ml of saline flush. The contrast agent will be divided into two equal doses for stress and rest perfusion (0.05 ml/kg per perfusion). The stress agents used will be Adenosine (short-term infusion at 140 µg/kg/min using an infusion pump) or Regadenoson (400 µg intravenous bolus). Patients with relative or absolute contraindications to stress testing will be excluded from the study, including those with acute coronary syndrome, life-threatening arrhythmias, severe COPD, second- or third-degree AV block, and patients with contraindications to MRI (ferromagnetic implants, severe renal failure, pregnancy). The MRI protocol monitors contrast agent passage through the myocardium and subsequent washout for at least one minute in selected cardiac slices (typically three parallel short-axis slices from the apex to the base of the left ventricle). During the examination, basic physiological parameters are continuously monitored, including ECG, blood pressure, oxygen saturation (pO₂), and respiration. If necessary, the stress effect of the administered agent can be immediately reversed by administration of, for example, aminophylline. During scanning, changes in contrast concentration (signal intensity) are tracked over time. A targeted perfusion sequence (Philips DYNs\_BTFE\_3sl) will be used. For quantification purposes, this sequence will be complemented by a very short labeling sequence, which enables quantitative calculations while leaving the dynamic and pharmacological characteristics of the main perfusion sequence unaffected. After the examination, quantitative parameters from the perfusion sequence will be calculated to obtain the required perfusion metrics. Analysis of the main perfusion parameters and other common cardiovascular metrics will be performed using Philips IntelliSpace Portal and CVI42 software. The objective of the project is to optimize the scanning and evaluation process of stress perfusion MRI towards full quantification of measurement results, through collaboration between the clinical site and the MRI system manufacturer.

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