Diagnostic value of nuclear cardiology in coronary artery disease

This thesis investigates the diagnostic value of cardiac positron emission tomography when compared to single photon emission computed tomography for detection of coronary artery disease. This prospective study involves comparison of myocardial perfusion single photon emission computed tomography with coronary calcium scores; optimization of nuclear cardiac protocols in cardiac phantom experiments; and determination of diagnostic performance of cardiac positron emission tomography in the evaluation of myocardial viability in patients with significant coronary disease

PET imaging of ischaemic myocardial injury and angiogenesis

The myocardium of patients with coronary artery disease (CAD) often is a mixture of ischaemic but viable tissue and irreversibly injured scar tissue. The viable tissue has capability of functional recovery after restoration of blood flow and the assessment of myocardial viability is important in identifying patients who will most likely benefit from revascularisation. Angiogenesis is an essential part of the healing process after ischaemic myocardial injury aiming at restoration of intact tissue capillary network. Measurement of myocardial blood flow by positron emission tomography (PET) and [15O]water is widely used in the evaluation of CAD, but its value in the assessment of myocardial viability is incompletely understood. [68Ga]NODAGA-RGD is a novel PET tracer binding to αvβ3 integrin that plays a central role in angiogenesis and therefore, may enable imaging of angiogenic activity. The purpose of this thesis was to evaluate [15O]water and [68Ga]NODAGA-RGD for the assessment of myocardial viability and ischaemic myocardial injury by PET in experimental models. We used pig models of surgically or percutaneously induced coronary stenosis and human cell based in vitro model of angiogenesis. In the first substudy, we found that resting myocardial blood flow (MBF), perfusable tissue fraction (PTF) and perfusable tissue index (PTI) by [15O]water PET detected myocardial viability with good accuracy in pig models of ischaemic heart failure and myocardial ischaemia. In the second substudy, we found that [68Ga]NODAGA-RGD demonstrated increased myocardial αvβ3 integrin expression in the ischaemic myocardium that was localised in the irreversibly injured myocardium. In the third substudy, we found that the uptake of [68Ga]NODAGA-RGD was proportional to angiogenic activity in an in vitro angiogenesis tissue model. In conclusion, these experimental studies indicate that resting MBF, PTF and PTI by [15O]water PET are useful indexes of myocardial viability in chronic CAD. [68Ga]NODAGA-RGD PET may be useful for the identification of αvβ3 integrin activation associated with recent ischaemic myocardial injury. This tracer reflects angiogenetic activity in vitro, but its specificity for angiogenesis in vivo remains uncertain.Sydänlihaksen iskeemisen vaurion ja uudisverisuonituksen PET kuvantaminen Sepelvaltimotautipotilaiden sydänlihas koostuu usein iskeemisestä, mutta elinkykyisestä ja peruuttamattomasti vaurioituneesta kudoksesta. Elinkykyisen sydänlihaksen toiminta voi palautua normaaliksi verenkierron palauttamisen jälkeen, ja elinkykyisyyden arviointi on tärkeää verenkierron palauttamisesta hyötyvien potilaiden tunnistamisessa. Uudisverisuonitus eli angiogeneesi, jonka tarkoitus on palauttaa kudokseen toimiva hiussuoniverkosto, on tärkeä osa iskeemisen vaurion jälkeistä paranemista. Sydänlihaksen verenvirtauksen mittaaminen positroniemissiotomografialla (PET) käyttäen merkkiaineena [15O]vettä on paljon käytetty menetelmä sydäntaudin arvioinnissa, mutta sen soveltuvuutta sydänlihaksen elinkykyisyyden arviointiin ei tiedetä. [68Ga]NODAGA-RGD on uusi angiogeneesiä säätelevään αvβ3 integriiniin sitoutuva merkkiaine jonka avulla voitaisi mahdollisesti kuvantaa sydänlihaksen angiogeenistä aktiivisuutta. Väitöskirjatyön tarkoituksena oli arvioida [15O]vesi ja [68Ga]NODAGA-RGD PET:n käyttökelpoisuutta sydänlihaksen elinkykyisyyden ja iskeemisen sydänlihasvaurion tunnistamisessa kokeellisilla malleilla. Käytimme sikoja, joille oli aiheutettu sepelvaltimotukos kirurgisesti tai katetrisaatiolla, sekä ihmissolupohjaista kokeellista angiogeneesin kudosmallia. Ensimmäisessä osatyössä havaitsimme, että [15O]vesi PET:n tehokkuus elinkykyisyyden havaitsemisessa iskeemisen sydämen vajaatoiminnan ja sydänlihasiskemian sikamalleissa oli hyvä. Toisessa osatyössä havaitsimme, että [68Ga]NODAGA-RGD:llä voitiin havaita lisääntynyt αvβ3 integriiniaktivaatio, joka sijaitsi peruuttamattomasti vaurioituneessa sydänlihaksessa. Kolmannessa osatyössä havaitsimme, että [68Ga]NODAGA-RGD:n kertymä oli verrannollinen angiogeneesiaktivaatioon kokeellisessa angiogeneesin kudomallissa. Yhteenvetona voidaan todeta, että [15O]vesi PET on käyttökelpoinen sydänlihaksen elinkykyisyyden arvioinnissa kroonisessa sepelvaltimotaudissa. [68Ga]NODAGA-RGD PET voi olla käyttökelpoinen tuoreeseen sydänlihasvaurioon liittyvän αvβ3 integriiniaktivaation kuvantamisessa. Tämä merkkiaine kuvastaa angiogeenistä aktivaatiota kokeellisesti, mutta sen tarkkuus elävässä elimistössä on epäselvää

Tracers for Cardiac Imaging: Targeting the Future of Viable Myocardium

Ischemic heart disease is the leading cause of mortality worldwide. In this context, myocar- dial viability is defined as the amount of myocardium that, despite contractile dysfunction, maintains metabolic and electrical function, having the potential for functional enhancement upon revascular- ization. Recent advances have improved methods to detect myocardial viability. The current paper summarizes the pathophysiological basis of the current methods used to detect myocardial viability in light of the advancements in the development of new radiotracers for cardiac imaging

Scope of emission tomography for assessment of myocardial viability in patients with coronary artery disease

This thesis deals with the clinical and difficult problem of identifying viable myocardium in patients with coronary artery disease and chronic wall motion abnormalities that may improve after coronary revascularization. Assuming that viable myocardium is chronically hypoperfused, "hibernating myocardium", and with reduced wall motion properties, we attempted to investigate the predictive power of pre-revascularization status of flow and glucose metabolism using positron emission tomography techniques in myocardium at risk that would be able to improve after restoration of the coronary circulation. This thesis aims to further assess the pathophysiology of hibernating myocardium using emission tomography. For this purpose, absolute measurements of regional myocardial blood flow in ml/min/g and metabolic rate of glucose utilization in μ/min/g during hyperinsulinaemic euglycaemic clamp, using positron emission tomography was performed. One hundred patients with hibernating myocardium were studied. All patients underwent radionuclide ventriculography before surgery and thirty before and after surgery. These thirty patients with follow-up scans will be the object of the present study. Control values for myocardial blood flow and metabolic rate of glucose utilization were obtained respectively in twenty five and nine age matched normal volunteers. This thesis is composed of eight chapters. The first four chapters review the available literature dealing with similar problem, myocardial viability definition, regulatory mechanism of coronary blood flow and methodology available to study hibernating myocardium, particularly positron emission tomography in chapter five the materials, subjects and methodology, as well as protocols employed in this thesis are described. Chapter six describes all the results pointing to the predictive accuracy of positron emission tomography measurements of flow and metabolism in determining viable myocardium pre-myocardium. Chapter seven discusses these results in the light of available literature and state the main conclusions. Finally, some thoughts for further research in the subject are exposed

New nuclear medicine techniques for the assessment of myocardial viability

Een dotterbehandeling of een bypassoperatie heeft alleen zin als er nog voldoende hartspierweefsel over is dat zich kan herstellen. Momenteel wordt de vitaliteit van de hartspier voor de ingreep nog onderzocht met een PET-scan, maar deze techniek is duur en maar in een paar ziekenhuizen in Nederland aanwezig. Riemer Slart constateert in zijn proefschrift dat een goedkopere scan het succes van een bypass of dotteren ook kan voorspellen.

Hybrid positron emission tomography–magnetic resonance of the heart:current state of the art and future applications

Hybrid Positron Emission Tomography-Magnetic Resonance (PET-MR) imaging is a novel imaging modality with emerging applications for cardiovascular disease. PET-MR aims to combine the high spatial resolution morphological and functional assessment afforded by MRI with the ability of PET for quantification of metabolism, perfusion and inflammation. The fusion of these two modalities into a single imaging platform not only represents an opportunity to acquire complementary information from a single scan, but also allows motion correction for PET with reduction in ionising radiation. This article presents a brief overview of PET-MR technology followed by a review of the published literature on the clinical cardio-vascular applications of PET and MRI performed separately and with hybrid PET-MR

Hypodense regions in unenhanced CT identify nonviable myocardium: validation versus 18F-FDG PET

Purpose: The aim of the present study was to evaluate the accuracy of hypodense regions in non-contrast-enhanced cardiac computed tomography (unenhanced CT) to identify nonviable myocardial scar tissue. Methods: Hypodense areas were visually identified in unenhanced CT of 80 patients in the left ventricular anterior, apical, septal, lateral and inferior myocardium and CT density was measured in Hounsfield units (HU). Findings were compared to 18F-fluorodeoxyglucose uptake by positron emission tomography (FDG PET), which served as the standard of reference to distinguish scar (<50% FDG uptake) from viable tissue (≥50% uptake). Results: Visually detected hypodense regions demonstrated a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 74, 97, 84 and 94%, respectively. A receiver-operating characteristic (ROC) curve analysis revealed a cutoff value of mean HU at <28.8 for predicting scar tissue with an area under the curve of 0.93 yielding a sensitivity, specificity, PPV and NPV of 94, 90, 67 and 99%, respectively. Conclusion: Hypodense regions in unenhanced cardiac CT scans allow accurate identification of nonviable myocardial scar tissu