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Major public health issues and common pathologies
Cardiovascular diseases are the leading cause of death worldwide, making it a major public health issue. Coronary heart disease was the world leading cause of death in 2004 with 7.2 millions of deaths, which represents 12.2% of overall deaths. Chronic cardiovascular diseases impacts particularly high-income countries. Ischemic cardiomyopathy alone, when oxygen supply to the heart is critically reduced, was responsible for 8% (~40 000 cases) of deaths in France in 2006, and all circulation diseases account for the second cause of death (28%) after tumors (30%){source: INSEE, CépiDc-Inserm }.
The increasing mortality rate related to cardiovascular death leads to growing interest and investments from governments in the topic. Major risks of cardiovascular disease come from new life style in wealthy countries and the same behavior in developing countries is becoming an important public health concern. Increased stress, too rich diet and reduced physical activity are reasons for increasing risk of heart failure and vascular pathology. Therefore investments go to both research and prevention, in order to improve health care as well as raise public awareness.
Cardiac imaging: purpose and techniques
Cardiac imaging stands as one of the top priorities towards improving health care, to provide better and more accessible care to the numerous cardiovascular patients. Cardiac imaging is required to provide accurate diagnosis as well as tools for treatments evaluation.
Diagnosis
Imaging is at the core of identification, diagnosis and follow-up for all major cardiovascular diseases today. While biomarkers enables the detection of abnormality and triggers disease suspicions, imaging helps pathology detection and treatment choice. Accurate diagnosis helps to define treatments targets and guides chirurgical intervention.
Moreover imaging is a key to provide the follow-up to assess treatment efficiency. Subsequent treatment adjustments rely heavily on the radiologists’ conclusion.
Finally imaging also helps in new treatments evaluation, particularly for the heart which is difficult to access and analyze in vivo.
Prognosis
Aging as well as long-term diseases such as diabetes and obesity can impact severely the vascular system, including the heart. The mechanisms behind the complications are not always well understood and certainly not easy to anticipate. Cardiac imaging has an important role of prognostic to play in the detection and the prevention of such complications before trauma occurs. Many other diseases or dangerous genetic background are potential sources of future trauma and require regular check-ups. Accurate assessment of the current state of the body health in its deep foundations, especially the heart and the circulatory system, is needed to develop an efficient prevention.
Techniques: advantages and limitations
Cardiac imaging is giving a lot of interests towards many different applications. However imaging the heart is difficult and encounters many limitations. Investigating the heart can be done through 4 main imaging techniques, each with its own advantages and drawbacks: Positron emission Tomography (PET), very specific but suffers low resolution and exposes patients to radiations; Ultrasounds, easily accessible and non-invasive, but can image only a limited depth and with relative quality; Cone-beam X-ray tomography (CT), which has a very good resolution but is difficulty specific and exposes patients to small radiations; Magnetic Resonance Imaging (MRI) which offers a good resolution and specificity totally non-invasively but suffers a limited accessibility, related to its important cost.
Magnetic resonance imaging (MRI) has several advantages such as being harmless and non-invasive and providing a wide range of information that enables the differentiations of many cardiac diseases. However MRI has the drawback of being expensive and is also one of the most complex medical imaging techniques actually used. Nuclear spins manipulation and subsequent signal detection works in the frequency space and a Fourier transform is needed to retrieve images spatial features. Therefore MRI development requires specific techniques implying combined state-of-the art mathematics and physics.
Although the first MR images were acquired 40 years ago, the complexity of an MR imaging acquisition process qualify it as a new imaging modality with a vast evolution potential and new breakthroughs are observed every year. The resolution and image quality is satisfactory although not as good as CT image quality. Finally MRI allows a wide variety of image contrasts that characterize tissues on variable basis so that many diagnosis can be performed (protons density, nuclear spins properties, etc) from a single MRI examination, with no harm for the patient. This access to different contrasts makes MR Imaging a technique of great potential in diagnosis for the cardiac muscle. Several contrast agents can also be employed in MRI: coated gadolinium (Gd) is the common one used to perform perfusion imaging but also ultra-small super-paramagnetic iron oxide (USPIO) are used as contrast agent in MRI. Gadolinium is coated because of its high toxicity if injected as is. Cardiac imaging benefits greatly from this contrast-enhanced imaging as it can determine the precise 3D localization and extent of an injury subsequent to a heart attack. Moreover MRI can access information from several nuclei. Common MRI is based on 1H resonance (water and organic tissues possess many 1H), but 31P MR spectroscopy (MRS) or 17O MRI are also interesting nuclei since 31P-MRS can measure myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) (Bottomley et Weiss 1998) and 17O MRI might able the quantification of oxygen consumption (McCommis et al. 2010). Thus MRI might enable to quantify the physiological tissues cells activity.
Among all imaging techniques, the choice to use one over the others is made depending on their diagnosis potential regarding suspected pathology but advantages and drawbacks like cost and accessibility are also taken in consideration and sometimes prevent any choice at all. This work focuses on cardiac MRI since many techniques are being developed in this field and benefit each other from their innovations (Lustig, Donoho, et Pauly 2007). Cardiac MRI is indeed a hot topic that currently motivates researchers worldwide.
Heart physiology
Introduction
To better understand the problematic of this thesis work, some basic knowledge of the cardiac physiology might be useful. This part is designed only for the basic understanding of the cardiac structure and function and focuses on their implication in the application of diffusion weighted magnetic resonance imaging to study the cardiac muscle.
Role of the heart
It might be obvious to some, but the heart plays a major role in the body system by circulating the blood from the lungs to the organs and backwards. The function of the heart acts as a double pump, propelling the deoxygenated blood to the lungs, where it is re-oxygenated, and then propelling the oxygenated blood towards all organs and tissues in the body (including the heart itself).
Figure 1: Blood circulatory system. The blood transports oxygen (in red) from the lungs, through the heart and to the body cells. Then the deoxygenated blood (blue) brings back carbon dioxide through the heart to the lungs to be expelled. Adapted from www.biosbcc.net .
Macroscopic heart anatomy
The human heart is about the size of a big fist and weights normally 250 to 350g. The heart functions as a double pump, decomposed in 4 cavities, with 4 valves separating each compartment:
• The atria: the right atria and the left atria, pre-chambers where flow is gathered
• The ventricles: the right ventricle and the left ventricle, where flow is propelled.
The two ventricles are separated by the septum wall. On each side, the valves function by pairs to open and close the entry and exit points of blood flow. When a chamber is full, the entry valve closes and the exit valve opens. When the chamber needs refill, the exit valve closes and the entry valve opens. The valves are controlled by the ventricles contraction through chordae tendineae (orange) taking roots in papillary muscles (small muscles in grey).
Figure 2: Heart anatomy focus. Abbreviations are: RA, right atria; LA, left atria; RV, right ventricle; LV left ventricle; T, tricuspid valve; P, pulmonic valve; A, aortic valve; M, mitral valve.
The two sides are very different as the right ventricle propels the deoxygenated blood to the lungs, very close to the heart and easy to access, while the left ventricle propels the oxygenated blood to all the organs, requiring a lot of strength. Therefore the left ventricle muscle is usually thicker than the right ventricle.
The heart muscle consists of a continuum (Streeter et al. 1970) that can be described with three adjacent layers: the epicardium, the thin outer layer (<1mm), the myocardium, the middle layer (~7-9mm) and the endocardium, the thin inner layer (<1mm).
The cardiac cycle
The cardiac cycle can be decomposed in 4 steps. The focus is usually brought on the left ventricle, more critical than the right ventricle since it expels blood to the body, feeding the organs with oxygenated blood. But the two sides, the two ventricles function simultaneously.
The four basic cardiac phases are:
a. Ventricular filling. The mitral valve is open. The ventricle dilates to fill blood in. (diastole)
b. Isovolumetric contraction. The mitral valve closes, the aortic valve remains closed. The ventricle contracts to increase the pressure in the ventricle.
c. Ejection. The aortic valve opens. The blood is ejected through the aorta to the body organs.
d. Isovolumetric relaxation. The aortic valve closes. The myocardium relaxes the pressure in the ventricle.
The cardiac cycle is usually simplified in two parts: the systole, active part of the cycle, includes phases b to d, and the diastole, passive part, the phase a where the blood filling dilates the relaxed myocardium. The cycle is accessible through its electrical activity that surface electrodes can capture. The reference being the strong R-wave corresponding to the trigger of the myocardium contraction (phase b). Most cardiac studies use the R-wave as the reference of time.
The myocardium microstructure
The cardiac muscle, the myocardium, is a very particular muscle in the human body that is a striated muscle as skeletal muscles, but involuntarily (contractile) as smooth muscles (e.g. autonomic nervous system of the eye).
There are three major types of cardiac cells (www.brown.edu):
• Cardiomyocytes – These are the cells that make up the contractile cardiac muscle. The cardiomyocytes are multinuclear such as cells in skeletal muscles (and contrarily to smooth muscles).
• Vascular endothelial cells – These cells are located in the inner lining of the heart blood vessels. They reduce turbulence of the flow of blood allowing the fluid to be pumped farther. They regulate blood flow through vasoconstriction and vasodilation. They also act as a selective barrier that controls molecules transit through capillary membranes.
• Smooth muscle cells – These are located in the wall of the heart’s blood vessels. They control the volume of blood vessels and the local blood pressure.
Table of contents :
1. Introduction
1.1. Clinical cardiac imaging: today’s challenges
1.1.1. Major public health issues and common pathologies
1.1.2. Cardiac imaging: purpose and techniques
1.1.2.1. Diagnosis
1.1.2.2. Prognosis
1.1.3. Techniques: advantages and limitations
1.2. Heart physiology
1.2.1. Introduction
1.2.2. Role of the heart
1.2.3. Macroscopic heart anatomy
1.2.4. The cardiac cycle
1.2.5. The myocardium microstructure
1.2.6. The coronary flow mechanics (Rossi 2007)
1.2.7. The myocardium global architecture
1.3. MRI
1.3.1. NMR principles
1.3.2. NMR experiment
1.3.2. MRI techniques: signal formation
1.3.3. MRI: Encoding spatial information
1.3.4. MRI hardware
1.4. Diffusion Weighted Magnetic Resonance Imaging (DW-MRI or DWI)
1.4.1. Diffusion theory
1.4.2. Diffusion encoding
1.4.3. Diffusion computation
1.4.4. DWI contrast and applications
1.4.5. DWI limitations
2. In vivo cardiac DWI: feasibility and development
2.4. In vivo C-DWI: limitations
2.5. In vivo C-DWI: previous achievements
2.5.1. Stimulated-echo approach
2.5.2. Spin-echo approach
2.6. In vivo C-DWI feasibility: analysis in a specified context
2.6.1. Tackling motion: slice thickness theoretical study
2.6.2. Cardiac motion model: Translation Model
2.6.3. Cardiac motion model: Rotation twist Model
2.6.4. Influence of slice thickness: experimental findings
2.6.5. Evolution of signal intensity with repetitions
2.6.6. Delineation of optimal time-window for cardiac DWI triggering
2.7. TMIP-DWI: a new approach to reduce DWI physiological motion sensitivity
2.7.1. Acquisition Method
2.7.2. Non-rigid Registration
2.7.3. TMIP initial results with home-made sequences
2.7.3.1. Spin-echo EPI sequence
2.7.3.2. Diffusion-preparation b-SSFP-DWI sequence
2.7.4. TMIP initial results with product sequence
2.8. PCA-TMIP-DWI: improving robustness and accuracy
2.8.1. PCA filtering
2.8.1.1. Image processing theory
2.8.1.2. PCA optimization
2.8.1.3. PCA experimental results
2.8.2. PCATMIP
2.8.2.1. Theoretical study of TMIP and PCATMIP on DWI images and parameters
2.8.2.2. In vivo results
2.8.2.3. Initial patients’ results
2.8.2.4. Discussion
2.8.2.5. Limitations
3. Conclusions and Outlooks
3.1. Conclusions and discussions
3.2. Perspectives
References
