The CARDIAC Project

Introduction

Heart attacks (or “myocardial infarctions”) are among the most frequent and most critical diseases in the industrialized world today. The most common reason why a heart attack occurs is that one of the coronary arteries normally supplying the heart with blood is blocked. As blood circulation is cut off, heart muscle cells begin to die and the heart can no longer function normally. Conventional cardiological procedures like angioplasty, where a balloon catheter is inserted into the heart and dilated to widen the occluded artery, are aimed at returning the blood circulation in the infarcted area, but can never revitalize damaged heart muscle cells.

Within the scope of several clinical studies, the General Hospital of Linz and the Red Cross Blood Center Linz developed an novel and innovative medical method addressing this problem: the treatment of myocardial infarctions with stem cells. In contrast to other cells of the body (e.g. blood cells, neural cells, muscle cells), stem cells do not yet fulfill a specific function and have the unique capability to develop into another type of cell. In this clinical context, stem cells are transplanted into the infarcted area of a patient’s heart where they are supposed to develop into heart muscle cells and thus regenerate heart muscle functionality.

Research on stem cells is criticized due to ethical reasons, when human embryos are sacrificed to harvest embryonic stem cells. But for this medical treatment, however, stem cells of the patient himself (also called “adult autologous stem cells”) are used and thus no ethical concerns arise.

The Problem

When patients suffer a myocardial infarction, cardiologists need to diagnose its location and its degree of damage. This is usually done with coronary angiography, where sequences of x-ray images of a patient’s heart are recorded. In addition to images of the coronary arteries that show which of the vessels are blocked, image sequences of the left heart chamber are recorded; they allow to analyze the contractility of the heart muscle that is surrounding the heart chamber. In our clinical studies, coronary angiography is done two times: immediately after myocardial infarction and about six months later. Images acquired by coronary angiography do not represent the monitored object in 3D, but only projections of the object. Consequently, only 2D information, namely the projection of the heart chamber, is available to cardiologists for diagnoses.

Coronary X-Ray Angiography
Left: Heart Chamber, Right: Coronary Arteries

Within the scope of the cardiac stem cell therapy, stem cells are transplanted into the infarcted area, where they are supposed to regenerate heart muscle functionality. Hence, the main interest of cardiologists and molecular biologists is:

• Which areas of the heart (muscle) contract at which extent?
• How does the contractility pattern look like?
• Are there (more) improvements in the areas of the heart where stem cells were transplanted?
• How can the improvements be measured objectively?

Improvements can be visually inspected by comparing x-ray images recorded after infarction to x-ray images recorded 6 months later. But images acquired by coronary angiography only provide limited diagnostic means, since merely the movement of the heart chamber’s contour is visible and heart contractility cannot be seen in 3D. Consequently, additional tools for analyses and diagnoses need to be developed to provide further feedback about the success of the therapy.

The Solution

The approach used within the CARDIAC project to address the mentioned issues in question and to overcome the limited diagnostic facilities of coronary angiography is based on the following idea: to develop a software system that enables cardiologists to reconstruct 3D models of the ventricle (heart chamber) from x-ray images and to use these models for clinical evaluation.

Compared to a 2D projective x-ray image, a single reconstructed 3D model already provides an improved data visualization for physicians. By further combining a time sequence of reconstructed 3D models, the CARDIAC software system derives a 4D model of the patient’s ventricle. This 4D model (the forth dimension is time) allows the animation of a heart beat and enables cardiologists to visually inspect regional heart muscle activity.

In addition to that, CARDIAC provides methods for ventricular wall motion analyses, whose results are then used to objectively quantify contractility. One method used for analysis and quantification is the computation of the distance covered by a point on the surface during motion; the shorter the covered distance, the lower the regional contractility. Results of wall motion analysis are projected onto the surface of the ventricular model and displayed using a color scheme. Thereby, areas of poor contractility are made even more recognizable and observable.

Color-Encoded Left Ventricular Wall Motion Analysis

Keeping in mind that two coronary angiographies are available for diagnosis, namely one immediately and one six months after infarction, two 4D ventricular models can be reconstructed and used by the software for clinical evaluation. To allow cardiologists to finally assess improvements of (local) contractility in selected areas of the heart muscle, CARDIAC provides means for comparing wall motion analyses of two 4D models. Due to these comparative analyses, improvements can be objectively measured and, again, visualized on the surface of the ventricle model using a color scheme.

From a scientific point of view, research activities do primarily, but not only, focus on digital image processing. Emphasis is also put on the development of new quantification possibilities for cardiology. Besides wall motion analyses based on reconstructed 4D ventricle models, novel medical diagnostic parameters derived from these models are provided. And “classic” diagnostic parameters, like for instance the ejection fraction (the cardiac output, calculated from the ventricular volume), are expected to be computed more accurately.

Both, the novel quantification possibilities and the improved visualization will help cardiologists and molecular biologists to analyze improvements of the heart muscle functionality and the success of the cardiac stem cell therapy. And although aimed at providing feedback about this special kind of therapy, the developed diagnostic and analysis tools can generally be used for other cardiac therapies or diagnosis, as well.