Michael G. Bateman

Accuracy of aortic annular measurements obtained from three-dimensional echocardiography, CT and MRI: human in vitro and in vivo studies

Objectives To determine the accuracy of calcium-containing rings measurements imaged by three-dimensional echocardiography (3DE), multi-slice CT (MSCT) and cardiac magnetic resonance (CMR) under ideal conditions against the true ring dimensions. To compare the accuracy of aortic annulus (AoA) measurements in ex vivo human hearts using 3DE, MSCT and CMR. To determine the accuracy of AoA measurements in an in vivo human model. Design 3DE, MSCT and CMR imaging were performed on 30 calcium-containing rings and 28 explanted human hearts. Additionally, 15 human subjects with clinical indication for MSCT underwent 3DE. Two experts in each modality measured the images. Main outcome measures Bias and intraclass correlation coefficient for accuracy of imaging measurements when compared with actual ring dimensions. Bias, intraclass correlation coefficient and variability were obtained: (1) when comparing explanted human heart AoA measurements from the two remaining imaging modalities with the most accurate one as determined from the ring measurements and (2) in in vivo human AoA measurements. Analysis was repeated on explanted heart subgroups divided by aortic valve Agatston score. Results Against the known ring dimensions, CMR had the highest accuracy and the lowest variability. MSCT measurements had high accuracy but wider variability and 3DE had the lowest accuracy with the largest variability. When 3DE and MSCT were compared with CMR, 3DE underestimated and MSCT overestimated AoA dimensions, but inter-measurement variability of 3DE and MSCT were similar. When divided by Agatston score, both 3DE and MSCT measurements were larger and showed greater variability with increasing calcium burden. The in vivo study showed that the correlation between 3DE and MSCT measurements was high; however, 3DE measurements were smaller than those measured with MSCT. Conclusions In the in vitro model, CMR measurements were the most accurate for assessing the actual dimensions suggesting that further investigations on its role in AoA measurement in TAVR are needed. However from the in vivo model, MSCT and 3DE are reasonable alternatives with the understanding that they can slightly overestimate and underestimate annular dimensions, respectively.

The Clinical Anatomy and Pathology of the Human Arterial Valves: Implications for Repair or Replacement

A thorough understanding of valvar anatomy is essential for design engineers and clinicians in the development and/or employment of improved technologies or therapies for treating valvar pathologies. There are two arterial valves in the human heart—pulmonary and aortic valves. Both are complex structures whose normal anatomical components can vary greatly between individuals. We discuss the anatomy, pathology, and challenges relating to transcatheter and surgical repair/replacement of the arterial valves in a translational manner. The high prevalence of aortic valvar pathologies in the burgeoning elderly population, coupled with poor clinical outcomes for patients who go untreated, has resulted in prolific spending in the research and development of more effective and less traumatic therapies. The accelerated development of therapies for treating arterial valves has been guided by anatomical information gathered from high-resolution imaging technologies, which have focused attention on the need for complete understanding of arterial valvar clinical anatomies. This article is part of a JCTR special issue on Cardiac Anatomy.

Comparative imaging of cardiac structures and function for the optimization of transcatheter approaches for valvular and structural heart disease

The detailed assessment of cardiac anatomy using multiple imaging modalities is essential to understand the high degree of variations that exist in human hearts (i.e., with and without pathologies). Additionally, such information should provide one with important insights regarding which imaging modality will best provide the required visualization of device placement via a given transcatheter approach. We describe here an unique set of such studies performed on either preserved heart specimens or within reanimated large mammalian hearts, including human (using Visible Heart® methodologies). Such anatomical and device-tissue interface knowledge is critical for both design engineers and clinicians that seek to develop and/or employ less invasive cardiac repair approaches for patients with acquired or congenital structural heart defects.

MRI Assessment of Pacing Induced Ventricular Dyssynchrony in an Isolated Human Heart

This study demonstrates the capabilities of MRI in the assessment of cardiac pacing induced ventricular dyssynchrony, and the findings support the need for employing more physiological pacing. A human donor heart deemed non‐viable for transplantation, was reanimated using an MR compatible, four‐chamber working perfusion system. The heart was imaged using a 1.5T MR scanner while being paced from the right ventricular apex (RVA) via an epicardial placed lead. Four‐chamber, short‐axis, and tagged short‐axis cines were acquired in order to track wall motion and intramyocardial strain during pacing. The results of this study revealed that the activation patterns of the left ventricle (LV) during RVA pacing demonstrated intraventricular dyssynchrony; as the left ventricular mechanical activation proceeded from the septum and anterior wall to the lateral wall, with the posterior wall being activated last. As such, the time difference to peak contraction between the septum and lateral wall was ∼125 msec. Likewise, interventricular dyssynchrony was demonstrated from the four‐chamber cine as the time difference between the peak LV and RV free wall motion was 180 msec. With the ongoing development of MR safe and MR compatible pacing systems, we can expect MRI to be added to the list of imaging modalities used to optimize cardiac resynchronization therapy (CRT) and/or alternate site pacing. J. Magn. Reson. Imaging 2010; 31: 466–469.

Design of a Novel Perfusion System to Perform MR Imaging of an Isolated Beating Heart

Isolated mammalian hearts have been used to study cardiac physiology, pharmacology, and biomedical devices in order to separate myocardial characteristics from the milieu of the intact animal and to allow for increased control over experimental conditions. Considering these benefits and that MRI is the “gold” standard for measuring myocardial function, it was considered desirable to have a system which would allow simultaneous MR imaging of an isolated beating heart. Here we describe a unique portable system, which enables physiologic perfusion of an isolated heart during simultaneous MR imaging. A two unit system was designed to physiologically support a large mammalian isolated heart during MR imaging were a modified Krebs-Henseleit perfusate was used as a blood substitute. The first unit, which resides in an adjacent support room next to the scanner, contains all electronically powered equipment and components (with ferromagnetic materials) which cannot operate safely near the magnet, including (1) a thermal module and custom tube in tube heat exchanger warming the perfusate to 38°C; (2) a carbogen tank (95% O2 5% CO2) and hollow fiber oxygenator; and (3) two centrifugal blood pumps which circulates and pressurizes the left and right atrial filling chambers. The second unit, which resides next to the magnet and is free of ferromagnetic materials, receives warmed, oxygenated perfusate from the first unit via PVC tubing. The isolated hearts were connected to the second unit via four cannulae sutured to the great vessels. A support system placed inside the scanner on the patient bed secured the hearts and cannulae in the correct anatomical position. To date, this system was tested in a 1.5 T Siemens scanner using swine hearts (n=2). The hearts were arrested with St. Thomas cardioplegia and removed via a medial sternotomy. After cannulation of the great vessels, reperfusion, and defibrillation, four-chamber and tagged short-axis cine loops were acquired using standard ECG gating. Tagged short-axis images obtained at the base, mid-ventricle, and apex were used to measure the following functional parameters for one heart: LV end-diastolic volume=38.84 ml, LV end-systolic volume=23.23 ml, LV stroke volume=15.6 ml, LV ejection fraction=40.18%, and peak LV circumferential strain=16%. The feasibility of MR imaging an isolated, four-chamber working large mammalian heart was demonstrated using a custom designed and built portable MRI compatible perfusion system. This system will be useful in studying in vitro cardiac function (including human hearts) and developing MRI safe biomedical devices and MRI guided therapies in a controlled setting.

In vitro images of a double orifice mitral valve in a reanimated human heart.

Using Visible Heart® methodologies [1] the heart from a 45 year old male (BMI 30.4, pre-op BP 145/70, HR 107, regular rhythm and normal heart tones), deemed not viable for transplant to a recipient patient, was explanted to an isolated heart apparatus. Briefly, this methodology utilizes a clear Krebs-Henseleit buffer to provide nutrients and oxygen to the heart and allow for native ex-vivo functionality while providing the opportunity to visualize the internal anatomy with endoscopes. Upon reanimation LV and LA pressures were 95/12mmHg and 13/15mmHg respectively during sinus rhythm. The patient’s heart presented with no signs of any other congenital pathology and a pre-operative ultrasound indicated a 65% LV ejection fraction, normal chamber dimensions and trivial mitral regurgitation. The double orifice mitral valve can best be defined as an incomplete bridge, situated toward the superior commissure of the valve and supported by the superolateral (anterolateral) papillary muscle. Shown here is a series of four screenshots of the valve in both systole (Figure 1 A&B) and diastole (Figure 1 C&D) from the left atrium (Figure 1 A&C) and the left ventricle (Figure 1 B&D). These images clearly show the fibrous connection between the mural (posteroinferior) and aortic (anterosuperior) leaflets in the central region. Interestingly, the chronic presence of the fibrous bridge in this patient has had seemingly negligible effect on overall cardiac performance. Functional video footage of the valve can be accessed via the link provided (An accompanying video for this article can be viewed on the Internet at http://ats.ctsnetjournals.org/content/volNUMBER/issueNUMBER/images/data/PAGE/DC1/FILENAME). Figure 1

Animal Models for Cardiac Valve Research

In the current regulatory climate, the Food and Drug Administration requires that all invasive cardiac devices are subjected to in vivo testing prior to human clinical trials and/or medical use. The most effective method for assessing the in vivo performance, durability, and biocompatibility of a novel heart valve therapy is through testing within the appropriate animal model. For replacement heart valves, preclinical testing is performed under strict regulatory guidelines to critically assess the performance of the device and the response of the host, by accurately replicating the intended human implantation procedure. This ensures the collection of relevant data and minimizes the potential for distress or discomfort to the test subject. The fundamental goals of a preclinical study are to report any detectable pathological consequences of the procedure, to report any macro- or microscopically detectable structural alterations in the device itself, and to histologically assess any thromboembolic material, inflammatory reactions, or degenerative processes. The success of a preclinical trial relies on careful protocol design, choosing the appropriate animal model, and adhering to the regulatory guidelines for Good Laboratory Practices. Importantly, the continued use of animal models in cardiac research has also benefited the field of veterinary science and, until in vitro and in silico methods provide suitable alternatives, will continue to be the most accurate assessment for the next generations of valve therapies.

The benefits of the Atlas of Human Cardiac Anatomy website for the design of cardiac devices

This paper describes how the Atlas of Human Cardiac Anatomy website can be used to improve cardiac device design throughout the process of development. The Atlas is a free-access website featuring novel images of both functional and fixed human cardiac anatomy from over 250 human heart specimens. This website provides numerous educational tutorials on anatomy, physiology and various imaging modalities. For instance, the ‘device tutorial’ provides examples of devices that were either present at the time of in vitro reanimation or were subsequently delivered, including leads, catheters, valves, annuloplasty rings and stents. Another section of the website displays 3D models of the vasculature, blood volumes and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. The website shares library images, video clips and computed tomography and MRI DICOM files in honor of the generous gifts received from donors and their families.

Imaging in the context of replacement heart valve development: Use of the Visible Heart® methodologies

In recent years huge strides have been made in the fields of interventional cardiology and cardiac surgery which now allow physicians and surgeons to repair or replace cardiac valves with greater success in a larger demographic of patients. Pivotal to these advances has been significant improvements in cardiac imaging and improved fundamental understanding of valvular anatomies and morphologies. We describe here a novel series of techniques utilized within the Visible Heart(®) laboratory by engineers, scientists, and/or anatomists to visualize and analyze the form and function of the four cardiac valves and to assess potential repair or replacement therapies. The study of reanimated large mammalian hearts (including human hearts) using various imaging modalities, as well as specially prepared anatomical specimens, has enhanced the design, development, and testing of novel cardiac therapies.

Detailed Anatomical and Functional Features of the Cardiac Valves

The use of high-resolution noninvasive imaging in modern cardiac clinics to collect detailed images of valve function has dramatically accelerated the understanding of functional human heart anatomy. In the healthy human, the cardiac valves determine the passage of blood through the heart. The atrioventricular valves open during diastole to allow the filling of the ventricles and close during systole (ventricular contraction), directing blood through the semilunar valves to the body; these valves, in turn, close during diastole to prevent the flow of blood back into the ventricle. By presenting a comprehensive review of the histology, functional anatomy, and morphology of the cardiac valves, this chapter promotes an understanding of the valve features that is required for valvar repair or replacement via either surgical or minimally invasive (transcatheter) means.