R.A. Baldewsing

Intravascular palpography for high-risk vulnerable plaque assessment.

Background:The composition of an atherosclerotic plaque is considered more important than the degree of stenosis. An unstable lesion may rupture and cause an acute thrombotic reaction. Most of these lesions contain a large lipid pool covered by an inflamed thin fibrous cap. The stress in the cap increases with decreasing cap thickness and increasing macrophage infiltration. Intravascular ultrasound (IVUS) palpography might be an ideal technique to assess the mechanical properties of high-risk plaques.Technique:Palpography assesses the local mechanical properties of tissue using its deformation caused by the intraluminal pressure.In Vitro Validation:The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen-vessel wall boundary has an 88% sensitivity and 89% specificity for identifying such plaques.In Vivo Validation:In vivo, the technique was validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than fibrous plaques (p < 0.001). The presence of a high-strain region at the lumenplaque interface has a high predictive value to identify macrophages.Patient Studies:Patient studies revealed high-strain values (1–2%) in thin-cap fibrous atheroma. Calcified material showed low strain values (0–0.2%). With the development of three-dimensional (3-D) palpography, identification of highstrain spots over the full length of a coronary artery becomes available.Conclusion:Intravascular palpography is a unique tool to assess lesion composition and vulnerability. The development of 3-D palpography provides a technique that may develop into a clinical tool to identify the high-risk plaque.Hintergrund:Die Zusammensetzung einer atherosklerotischen Plaque wird als wichtiger erachtet als deren Stenosegrad. Eine instabile Läsion kann aufbrechen und eine thrombotische Reaktion auslösen. Die Mehrzahl dieser Läsionen enthält einen großen lipidreichen Kern, der von einer dünnen entzündeten Kappe bedeckt ist. Der Stress in der Kappe erhöht sich mit abnehmender Dicke der Kappe und zunehmender Makrophageninfiltration. Die intravaskuläre Ultraschall- (IVUS-)Palpographie könnte die ideale Technik zur Beurteilung der mechanischen Eigenschaften von Hochrisikoplaques darstellen.Technik:Die Palpographie erfasst die lokalen mechanischen Eigenschaften von Gewebe mit Hilfe der durch den intravaskulären Druck erzeugten Deformation.In-vitro-Validierung:Die Methode wurde durch Untersuchung erkrankter Koronar- und Femoralarterien validiert. Insbesondere zwischen fibrösem und fetthaltigem Gewebe ließ sich ein hochsignifikanter Unterschied bezüglich der Gewebsdehnung feststellen (p = 0,0012). Zudem wurde der prädiktive Wert für die Diagnose einer vulnerablen Plaque untersucht. Eine Stelle mit hoher Dehnung an der Gefäßoberfläche hat eine Sensitivität von 88% und eine Spezifität von 89% für die Erkennung solcher Plaques.In-vivo-Validierung:In vivo wurde die Technik in einem atherosklerotischen Yucatan-Minischwein-Modell validiert. Auch diese Untersuchung zeigte höhere Dehnungswerte in fetthaltigen gegenüber fibrösen Plaques (p < 0,001). Zudem hat das Vorliegen hoher Dehnungswerte an der Plaqueoberfläche einen hohen prädiktiven Wert für die Erkennung von Makrophagen.Patientenstudien:Patientenstudien ergaben hohe Dehnungswerte (1–2%) in fetthaltigen Plaques mit dünner Kappe. Kalzifiziertes Material zeigte niedrige Dehnungswerte (0–0,2%). Durch die Entwicklung der dreidimensionalen (3-D) Palpographie wird die Identifikation von Stellen mit hohen Dehnungswerten im kompletten Koronarsystem möglich.Schlussfolgerung:Wie keine andere Methode gestattet die intravaskuläre Palpographie, Zusammensetzung und Vulnerabilität einer Läsion zu beurteilen. Die Entwicklung der 3-D-Palpographie stellt eine Technik zur Verfügung, die sich zu einem klinischen Hilfsmittel zur Identifizierung von Hochrisikoplaques entwickeln könnte.

Assessment of vulnerable plaque composition by matching the deformation of a parametric plaque model to measured plaque deformation

Intravascular ultrasound (IVUS) elastography visualizes local radial strain of arteries in so-called elastograms to detect rupture-prone plaques. However, due to the unknown arterial stress distribution these elastograms cannot be directly interpreted as a morphology and material composition image. To overcome this limitation we have developed a method that reconstructs a Youngs modulus image from an elastogram. This method is especially suited for thin-cap fibroatheromas (TCFAs), i.e., plaques with a media region containing a lipid pool covered by a cap. Reconstruction is done by a minimization algorithm that matches the strain image output, calculated with a parametric finite element model (PFEM) representation of a TCFA, to an elastogram by iteratively updating the PFEM geometry and material parameters. These geometry parameters delineate the TCFA media, lipid pool and cap regions by circles. The material parameter for each region is a Youngs modulus, E/sub M/, E/sub L/, and E/sub C/, respectively. The method was successfully tested on computer-simulated TCFAs (n=2), one defined by circles, the other by tracing TCFA histology, and additionally on a physical phantom (n=1) having a stiff wall (measured E/sub M/=16.8 kPa) with an eccentric soft region (measured E/sub L/=4.2 kPa). Finally, it was applied on human coronary plaques in vitro (n=1) and in vivo (n=1). The corresponding simulated and measured elastograms of these plaques showed radial strain values from 0% up to 2% at a pressure differential of 20, 20, 1, 20, and 1 mmHg respectively. The used/reconstructed Youngs moduli [kPa] were for the circular plaque E/sub L/=50/66, E/sub M/=1500/1484, E/sub C/=2000/2047, for the traced plaque E/sub L/=25/1, E/sub M/=1000/1148, E/sub C/=1500/1491, for the phantom E/sub L/=4.2/4 kPa, E/sub M/=16.8/16, for the in vitro plaque E/sub L/=n.a./29, E/sub M/=n.a./647, E/sub C/=n.a./1784 kPa and for the in vivo plaque E/sub L/=n.a./2, E/sub M/=n.a./188, E/sub C/=n.a./188 kPa.

An Inverse Method for Imaging the Local Elasticity of Atherosclerotic Coronary Plaques

The rupture of thin-cap fibroatheroma (TCFA) plaques is a major cause of acute coronary events. A TCFA has a trombogenic soft lipid core, shielded from the blood stream by a thin, possibly inflamed, stiff cap. The majority of atherosclerotic plaques resemble a TCFA in terms of overall structural composition, but have a more complex, heterogeneous morphology. An assessment of the material distribution is vital for quantifying the plaques mechanical stability and for determining the effect of plaque-stabilizing pharmaceutical agents. We describe a new automated inverse elasticity method, intravascular ultrasound (IVUS) modulography, which is capable of reconstructing a heterogeneous Youngs modulus distribution. The elastogram (i.e., spatial strain distribution) of the plaque is the input for the method, and is measured using the clinically available technique, IVUS elastography. Our method incorporates a novel divide-and-conquer strategy, allowing the reconstruction of TCFAs as well as heterogeneous plaques with localized regions of soft, weakened tissue. The method was applied to ex vivo elastograms, which were simulated from the cross sections of postmortem human coronary plaques. To demonstrate the clinical feasibility of the method, measured elastograms from human atherosclerotic coronary arteries were analyzed. One elastogram was measured in vitro; the other, in vivo . The method approximated the true Youngs modulus distribution of all simulated plaques, while the in vitro reconstruction was in agreement with histology. In conclusion, the IVUS modulography in combination with the IVUS elastography has strong potential to become an all-encompassing modality for detecting plaques, for assessing the information related to their rupture-proneness, and for imaging their heterogeneous elastic material composition.

Local Elasticity Imaging of Vulnerable Atherosclerotic Coronary Plaques

The material composition and morphology of vulnerable atherosclerotic plaque components are considered to be more important determinants of acute coronary syndromes than the degree of stenosis. Rupture of a plaque causes thrombogenic material to contact the blood, resulting in a thrombus. Rupture-prone plaques contain an inflamed thin fibrous cap covering a large soft lipid pool. Mechanically, rupture occurs when plaques cannot withstand the internal stresses induced by the pulsating blood. These stresses concentrate within/around the cap/edge, since the lipid pool cannot bear much stress. During plaque development these stresses further increase when caps become thinner, lipid pools become larger, or the difference in stiffness (modulus) between the cap and the lipid pool increases. Intravascular ultrasound (IVUS) strain elastography/palpography and IVUS modulus elastography are imaging techniques that assess local plaque elasticity (strain and modulus) based on the principle that tissue deformation (strain) by a mechanical stress is a function of its elastic properties (modulus). Combined use of these techniques provides clinicians an all-in-one modality for detecting plaques, assessing their rupture proneness and imaging their elastic material composition. This chapter describes the terminology and pathophysiology of vulnerable plaques and discusses the techniques behind, the methods for and the validations of the elasticity imaging techniques.

Comparison of finite elements model elastograms and IVUS elastograms acquired from phantoms and arteries

Knowledge of the Youngs modulus distribution of an atherosclerotic artery allows for differentiation between its components. Intravascular elastography generates an artifactual image of this Youngs modulus distribution. A finite element model (FEM) can assist in interpreting the elastogram and give its Youngs modulus distribution by inverse problem solution. Intravascular ultrasound (IVUS) measurements were performed on a hard phantom with soft eccentric plaque and an atherosclerotic coronary artery. The complex FEM geometry and Youngs modulus distribution were defined using a custom-made graphical user interface. Next elastograms were calculated from IVUS data and compared with FEM elastograms. IVUS and FEM elastograms showed excellent agreement in case of the phantom and a similar pattern in case of the artery. Strain values in the FEM elastogram appeared highly sensitive for variations in the Youngs modulus but not in the Poissons ratio.

Motion compensation for intravascular ultrasound palpography for in vivo vulnerable plaque detection

Intravascular ultrasound (IVUS) palpography assesses the mechanical properties of coronary arteries in vivo by radial strain measurements. This is accomplished by cross- correlating RF signals acquired at different systemic pressures. However, catheter motion due to cardiac activity causes misalignment of these signals, so that less strain estimates are obtained. Four motion compensation methods have been studied for correcting in-plane catheter rotation and translation. The best method, local block matching, achieved an increase of 15% in the number of strain estimates. Application of motion compensation methods improves IVUS palpography, resulting in better vulnerable plaque detection.

Intravascular Young's modulus reconstruction using a parametric finite element model

IntraVascular UltraSound (IVUS) elastography may be used to detect vulnerable, rupture prone plaques, which are held responsible for the majority of acute coronary syndromes. IVUS elastography accomplishes this by visualising local incremental radial strain of arteries, in so-called elastograms. These are an artifactual image of the Youngs modulus distribution and therefore, they cannot be directly interpreted as plaque component images. To overcome this limitation, we developed a modulography tool, which converts an elastogram into a modulogram, i.e. a Youngs modulus image. This tool is especially developed for reconstruction of plaques having a lipid pool covered by a cap. Reconstruction consists of matching the strain image output, calculated with a parametric finite element model (PFEM) representation of a vulnerable plaque, to an elastogram by iteratively updating the PFEM parameters. The modulography tool successfully reconstructed both geometry and composition of a vulnerable plaque, solely using an elastogram as input.

Quantitative intravascular ultrasound elasticity imaging as an imaging biomarker in clinical trials

The composition and morphology of an atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes that the degree of stenosis. When a lesion is unstable, it can rupture and cause an acute thrombotic reaction. An unstable plaque can be characterized by a lipid core that is covered by a thin fibrous cap, which has been locally weakened by inflammatory cells. Intravascular Ultrasound Palpography is an intravascular ultrasound based technique that is capable to measure the local strain in coronaries and atherosclerotic plaque. This strain is induced by varying intraluminal pressure. This lecture will show principles of the technology and how this technology is used in clinical trials. Results from a trial with traditional lipid lowering treatment (IBIS1) and from a trial on the efficacy of a new medication (IBIS2) will be presented. Furthermore the potential of Intravascular Ultrasound Modulography will be discussed. This work is financially supported by the...

3D intravascular ultrasound palpography for vulnerable plaque detection

When a lesion is unstable, it may rupture and cause an acute thrombotic reaction. A rupture prone plaque contains a large lipid pool covered by a thin fibrous cap. Intravascular ultrasound (IVUS) elastography can assess the presence of lipid pools and identify high stress regions. The deformation of the tissue is determined using ultrasound. For intravascular purposes, the intraluminal pressure is used as the excitation force. The radial strain in the tissue is obtained by cross-correlation techniques on the radio frequency (rf) signal. The strain is colour-coded and plotted as a complimentary image to the IVUS echogram, or, in case of palpography, as a ring on the lumen vessel boundary.

Young's modulus reconstruction for assessing vulnerable atherosclerotic plaque composition in vivo

Intravascular ultrasound (IVUS) elastography visualizes local arterial radial strain in a so-called elastogram to detect vulnerable, rupture-prone plaques. However, due to the unknown arterial stress distribution, this elastogram cannot be directly interpreted as a plaque composition image. To overcome this limitation, we have developed a method that reconstructs a Youngs modulus image from an elastogram. This method could successfully reconstruct a plaque from an elastogram that was measured from vessel-mimicking material and measured in vitro from a human coronary plaque. Finally, it was applied on an elastogram measured in vivo from a coronary plaque of a patient.