Cardiovascular System

Mechanobiology – a new concept for the prediction, diagnosis and monitoring of remodelling cardiovascular disease

3D and 4D Adaptive Filtering for Image Denoising and Patient Safety

The aim of this medical image science project is to increase patient safety in terms of improved image quality and reduced exposure to ionizing radiation in CT. The means to achieve these goals is to develop and evaluate an efficient adaptive filtering (denoising/image enhancement) method that fully explores true 3D and 4D image acquisition modes. Four-dimensional (4D) medical image data are captured as a time sequence of image volumes. During 4D image acquisition, a 3D image of the patient is recorded at regular time intervals. The resulting data will consequently have three spatial dimensions and one temporal dimension. Increasing the dimensionality of the data impose a major increase the computational demands. The initial linear filtering which is the cornerstone in all adaptive image enhancement algorithms increase exponentially with the dimensionality. On the other hand the potential gain in Signal to Noise Ratio (SNR) also increase exponentially with the dimensionality. This means that the same gain in noise reduction that can be attained by performing the adaptive filtering in 3D as opposed to 2D can be expected to occur once more by moving from 3D to 4D.

Absolute Quantification of Multinuclear Magnetic Resonance Spectroscopy

The major aim of this project is in collaboration with several clinics to expand the scope of medical magnetic resonance methods of water to a large number of metabolites and other functional tissue properties in order to significantly enhance the level of todays applications of clinical MR. The work covers developing novel acquisition technologies and hardware, as well as clinical applications of quantitative molecular spectroscopy and imaging. A major long-term aim is to shift MR-applications from a qualitative to a quantitative mode.

Application of novel image filters to MR image data

Background: Although time taken for completing MR exams has decreased substantially in recent past, it is still considerably longer than some other imaging examinations such as CT scanning. Radiologists have to manage a careful balance between examination duration and image quality. Image filters have been applied in past to CT, plain film radiography, and ultrasound. Purpose and scientific questions: The aim of our study is to assess if special 3D image filters can help quality of MR images compared to unprocessed and 2D filtered images. Another scientific question pertains to reduction of time required for performing MR examination with 3D filters. Most important variables: Image quality of MR images with and without application of the image filter will be compared by multiple independent radiologists. Assessment of image quality will include both the standard deviation of the MR signal as well as the subjective assessment of the image quality by multiple radiologists. Time saved with the use of 3D filters will be estimated for each subject. Advances in Knowledge and significance: Use of 3D filters for enhancing MR capabilities has not described before. Our study intends to determine if 3D filters for MR exams can help improve image quality and/or aid in reducing MR examination duration compared to use of either no filter or 2D filters. If found useful, the 3D filters will help us improve patient throughput in MRI and at the same time will enhance image quality of MR images.

Application of novel iterative reconstruction algorithms (IRA) and noise reduction filters (NRF) for reducing CT radiation dose

Background: Worldwide there have been concerns about increased risk of cancer with radiation dose from CT scanning. Reduction of radiation dose from CT will also decrease the risk of radiation induced cancer. Therefore, several techniques such as automatic exposure control techniques, and bow tie filters have been developed and assessed to reduce radiation dose with CT. Despite these developments, the radiation dose with CT scanning continues to increase each year as number of CT examinations performed each year keeps on increasing. Purpose and scientific questions: The aim of our study is to acquire low radiation dose CT data and assess if iterative reconstruction algorithms (IRA) and advanced noise reduction filters (ANRF) techniques can help improve image quality and acceptability of low dose CT images. Most important variables: CMIV has recently obtained access to novel IRA and NRF techniques for improving image quality of low dose CT images. Dose reduced CT images typically have higher noise and lower signal to noise ratio. We believe that IRA and ANRF, which work in different data domains to improve image quality and enable acquisition of low radiation dose CT. After acquisition of CT image data at different lower dose levels, we will independently process the data with IRA and ANRF and see if there is an improvement in the image quality with these techniques. The intent will be to see if variables such as image noise, artifacts, image contrast, sharpness as well as lesion conspicuity on low dose post processed images are similar to unprocessed higher dose images. In addition, quantitative measures of image quality such as quantitative image noise, and contrast to noise ratio will be performed. Advances in Knowledge and significance: This study will give information on use of IRA and ANRF for reducing radiation dose to patients undergoing CT scanning and quantify need and advantage of IRA and ANRF over unprocessed CT images reconstructed using conventional filtered back projection technique. If found useful, these techniques will help cut the radiation dose without sacrificing image quality, a result that may help save radiation dose from CT scanning.

Cardiovascular blood flow assessment

The primary purpose of the cardiovascular system is to drive, control and maintain blood flow to all parts of the body. Despite the primacy of flow, cardiovascular diagnostics still rely almost exclusively on tools focused on morphological assessment. Powerful techniques emphasizing blood flow assessment are needed. Phase contrast magnetic resonance imaging (PC-MRI) allows flow quantification in three dimensions and in three directions. Recently, our group has presented a generalization of the PC-MRI technique, which utilizes not only the signal phase to quantify the mean velocity of a voxel, as in conventional velocity mapping, but also the signal magnitude to quantify the distribution of the velocities within the voxel. We will exploit this feature in order to develop methods for the assessment of wall shear stress, turbulent stresses, and pressure loss in both laminar and turbulent cardiovascular blood flow. Validation of these tools will be performed in phantom studies by comparison with laser Doppler anemometry and computational fluid dynamics simulations, in addition to in-vivo studies. The techniques developed thereby will initially be used to assess patients with aortic coarctation, prosthetic aortic valve, dilated cardiomyopathy, and mitral valve insufficiency.

Determining Optimal non-invasive Parameters for the Prediction of Left vEntricular morphologic and functional Remodeling in Chronic Ischemic Patients (DOPPLER-CIP)

Coronary artery disease (CAD) remains the primary cause of cardiovascular morbidity and mortality in Europe. In current clinical practice, patients with chronic CAD are followed using non-invasive imaging methodologies for possible adverse morphologic remodelling and functional recovery of the myocardium before the decision for invasive examinations and treatments is taken. Technological developments have brought about several newer imaging methodologies (and associated parameters) that have shown accurate prognostic results under study conditions in selected patient populations. Each of these methodologies offers intrinsic advantages and disadvantages due to the physiologic processes it tries to assess, due to the technology it requires or due to its availability (often determined by its associated cost). However, to date, no large scale studies have made a direct comparison of the different methodologies towards predicting adverse morphologic remodelling or functional recovery of the myocardium after medical therapy. The lack of such information results in a sub-optimal use of the methodologies at hand. The aim of DOPPLER-CIP is therefore to conduct a multi-centre clinical study including about 1200 patients in order to determine the optimal prognostic parameters derived from (new) non-invasive imaging for a patient presenting with suspected chronic ischemic heart disease. The modality used to extract these parameters is of secondary importance. However, as both the accuracy and the cost related to extracting a particular parameter is modality-dependent, DOPPLER-CIP will also make a cost-effective analysis in order to determine which modality should preferentially be used to extract the clinically most relevant parameter. The study is financed by the European Union and is coordinated from Leuven, Belgium with cooperating centers in Linkoping, London, Madrid, Oslo, Pisa and Turku. Several add-on studies in Linköping will have access to this wealth of patient data for more in-depth analysis of wall motion and blood flow.

Effect of reperfusion on infarct size and cardiac function evaluated with MRI and echocardiography - MrSTEMI

Mechanical opening of the infarct related artery (primary PCI) in patients with ST-elevation myocardial infarction (STEMI) seems to produce better results than iv thrombolysis. Our hypothesis is that primary PCI saves myocardium, that the size of myocardial damage is best quantified with contrast-enhanced MR (CEMR), that salvaged myocardium translates into better cardiac function, and that the time to opening of the artery is directly related to the size of the infarct. We will attempt to study the effect of the delay between the start of symptoms and the opening of the infarct related artery. The infarct risk area will be estimated from echocardiography performed in the cath lab during initiation of treatmentand expressed in terms of wall motion score index, WMSI. The final damage will be assessed from a comprehensive MR study with late enhancement performed at 6 weeks post PCI.

HEART4FLOW - Improved Diagnosis and Management of Heart Disease by 4D Blood Flow Assessment

The primary purpose of the cardiovascular system is to drive, control and maintain blood flow to all parts of the body. Despite the primacy of flow, cardiac diagnostics still rely almost exclusively on tools focused on morphological assessment. The objective of the HEART4FLOW project is to develop the next generation of methods for the non-invasive quantitative assessment of cardiac diseases and therapies by focusing on blood flow dynamics, with the goals of earlier and more accurate detection and improved management of cardiac diseases.

Histological and functional effects of aortic valve disease on left ventricular function prior to and after surgical intervention

This research project aims to apply, modify and validate cardiac magnetic resonance imaging (cMRI) as a diagnostic tool for identification of fibrotic changes in the heart muscle due to pressure and volume overload caused by aortic valve disease. Furthermore, we hypothesize that these tissue changes (the amount and the location of the fibrotic tissue) can be connected to the impairment of the left ventricular function (LVF) in the advanced natural history of aortic valve disease. By using cMRI we hope to gain further information by non-invasive means on whether this impairment is reversible following surgical therapy. In addition to histological and functional studies at rest we plan to survey the anaerobe (physical) capacity of the study persons by performing cardiopulmonary exercise testing pre- and postoperatively and study the relationship between physical performance capacity and left ventricular function (LVF).

Implementation of Synthetic MRI into the clinical workflow.

Synthetic MRI is the approach of rapid quantification of MRI parameters and the subsequent synthesis of a whole range of contrast images based on the quantified data. This implies that a single scan is sufficient to generate any conventional T1- or T2 weighted image. It is even possible to visualize far stronger, non-physical contrast such as tissue specific imaging. Application of Synthetic MRI might save up to a third of the patient examination time and will make MRI more reliable and quantitative. The project aims at the clinical implementation of the approach into the PACS system. The technique of rapid quantification is more or less mature but the general use of Synthetic MRI in daily clinic needs to be introduced and validated. In addition to the investigation of the quality of the resulting images the specification of the time-saving aspect will be important. Cardiac Late Enhancement is implemented first and the validation is on-going. Synthetic Brain imaging is implemented at the moment. Future directions will concern the liver.

Low-dose Computed Tomography below 1 milliSievert

The purpose of this prospective study is to assess if CT images acquired with less than 1 mSv can provide diagnostic information similar to that obtained with current standard of care CT scanning. In this study, we will assess if currently used filtered back projection (FBP) technique or newer full and hybrid iterative reconstruction techniques (IRT) can provide diagnostically acceptable CT images with less than 1 mSv radiation dose. We will enroll 100 adults each from CT of head, chest, abdomen-pelvis, heart. All examinations will be performed at CMIV using the dual-source CT there. The raw data from low dose acquisitions is reconstructed with different iterative reconstruction parameters. The resulting image series are compared with the standard-of-care CT images according to both objective and subjective parameters. The project is done in collaboration with Mannudeep Kalra MD PhD and former visiting researcher at CMIV, now at MGH and Harvard medical school, Boston, USA.

Manifold-Valued Signal Proocessing

A manifold is a mathematical concept which generalizes surfaces to higher dimensions. Examples of 2-dimensional manifolds are for instance the surface of a sphere and the the surface of a torus, both being examples of non-linear manifolds. Locally however, manifolds are flat and equivalent to the an Euclidean space. Features found in signals can often be described using manifolds. This is often not stated explicitly, but instead various parameterizations of manifolds are used. In order to describe a quantity which can be seen as a point on a sphere, spherical coordinates are commonly used. This has some drawbacks however which we wish to avoid if possible. We see a need for manifolds in the field of medical image analysis. Medical doctors express a wish to objectively quantify various features in medical images, such as local texture, shape and orientation of organs. We know from previous research that manifolds can do the job, but we lack a generic framework for dealing with manifold-valued signals in signal processing. In fact, we believe that such a framework will be useful in other areas signal processing too. The goal of this project is to explore a specific flavour of signal processing and continue the development of methods 1) to learn or identify manifold-valued representations from examples and 2) apply signal processing on manifold-valued signals which is analogous to filtering and interpolation using convolution operators in classic signal processing.

Medical applications of electron paramagnetic resonance imaging (EPRI)

Radicals play crucial roles in a wide variety of physiological functions such as inflammatory response and regulation of blood flow, but are also involved in the pathology of various diseases such as atherosclerosis, cancer and Alzheimer´s disease. EPRI has also successfully been used to quantitatively image oxygen pressure in tumours in small animals (e.g. mice). Imaging of radical distributions and identification of radical species is therefore valuable for applications in a large number of medical disciplines. The first Scandinavian electron paramagnetic resonance imaging (EPRI) spectrometer, with unique possibilities for imaging of radical distributions in vivo and in vitro, was installed at Linköping University during 2010. The specific aim of the present proposal is to use this new equipment for medical applications. Three specific applications are proposed: Imaging of radical distributions in atherosclerotic plaques for a better understanding of the evolving inflammatory reaction leading to atherosclerosis, imaging of radical distributions in matter irradiated with ionizing radiation for dosimetry and imaging of oxygen pressure in tumours in mice.

Myocardial perfusion analyzed with realtime cardiac CT and according to the principle of dual energy

Bakgrund och syfte: Vid stabil kärlkramp finns förträngningar i hjärtats kranskärl som medför att blodflödet vid ansträngning inte kan ökas i behövlig grad; det uppstår syrebrist i hjärtmuskeln och man känner (i de flesta fall) smärta. Bröstsmärta kan dock uppkomma av flera andra anledningar. Ett sätt att ställa diagnosen kärlkramp är att ta bilder av hur mycket blod som kommer till hjärtmuskeln under ansträngning. Ett vanligt sätt att göra det är med isotopundersökning av hjärtat, varvid man behandlas med kärlvidgande läkemedel och ett spårämne insprutas i blodbanan. Vid MR-undersökning kan idag såväl insköljningsförloppet av kontrast följas för diagnostik av syrebrist och infarktstorlek mätas som kontrastupptag med s.k. late enhancement-teknik. Vid CT-angiografi av kranskärlen insprutas kontrast för kärlvisualisering, men på ett likartat sätt som vid MR kan vi idag med Siemens Dimension FLASH följa insköljningsförloppet i realtid (singelenergi) och detektera blodmängden i hjärtväggen (dubbelenergi) och till slut även mäta en sen kontrasteffekt, s.k. late enhancement.

New Clinical Quality Level for Medical Image Volumes

Image processing of medical image volumes (3D/4D data) requires a completely new approach compared to standard images (2D). Research on methods for high speed processing as well as for high image quality output is required. In a research project within the VINST programme a novel approach for solving the speed challenge was developed. Building on this “pre-study” project, this new project covers the remaining research for reaching a new clinical quality output level, while maintaining the speed. The goal is to have the research results from both projects verified in a prototype. The project is a cooperation between the company ContextVision AB and its research partner Center for Medical Image and Visualization (CMIV) at Linköping University.

New dimensions in ultrasound contrast imaging - Visualization of myocardial blood flow

Aims are: 1. To find new bubble excitation strategies for improved contrast/tissue ratio of the ultrasound image 2. To perform ultrasound pulse field and contrast bubble response simulations 3. To peruse corresponding in vitro experiments 4. To deliver the contrast optimized pulse sequences for implementation in echocardiographs (for clinical studies)

Postmortem imaging of myocardial infarction in correlation to autopsy.

The project aims on implementing MR imaging as a postmortem non-invasive investigation method for human corpses and on its validation on myocardial infarction cases compared to the cardiac autopsy findings. Furthermore, the MR scanning technique will be adapted to postmortem conditions that differ to some extent from the vital scanning conditions. This is especially true for the body core temperature and the missing of an ongoing circulation. The project is performed in a close collaboration of the CMIV and the Institute of Forensic Medicine in Linköping.

Reduction of Motion Artifacts in MRI

Cardiac Magnetic Resonance Imaging (MRI) is known to be degraded by respiratory motion during the scan. Previous methods to cope with these problems either impose a short scan time limit, prolong the scan or do not reduce the artefacts sufficiently. For time-resolved 3D phase contrast measurements of the cardiac flow and wall motion, the imaging time is already long, and image quality is of great importance. This projects aims to construct a reconstruction algorithm that is able to reduce the artefacts caused by respiration without prolonging the scan. This might be done by using a generalized reconstruction transform combined with an iterative optimization of an image quality metric.

Three-Dimensional Assessment of Cardiovascular Blood Flow

Blood flow dictates the form and function of the heart and blood vessels. Despite this, assessment of the cardiovascular system is predominantly based on anatomical descriptions rather than flow. Turbulent blood flow dominates the flow dynamics near clinically relevant regions such as valvular and vascular stenoses and prosthetic heart valves, but has been nearly overlooked in medical imaging. This incongruity is due mainly to inadequacies in imaging tools leading to a lack of insight into this topic. This project aims to create new tools and obtain new insights addressing persistent gaps in our understanding of complex cardiovascular macroflow by in-vivo assessment of laminar and turbulent blood flow in health and disease. Utilizing an innovative approach to phase-contrast magnetic resonance imaging combined with novel post-processing methods based on constitutive equations from fluid mechanics, we anticipate providing new methods for the assessment of stenoses and prosthetic heart valves. By studying patients with specific cardiovascular diseases, we expect to obtain new insights into the design of prosthetic heart valves, and the unique effects of different surgical approaches to valve replacement and to valvular and ventricular reconstruction.

Visualization of coronary arteries with virtual contrast injection

The aim of the project is to develop techniques that present the coronary arteries in CTA and MRA images in a format familiar for clinicians used to catheter angiography.