Craig J. Goergen

Cardiac Magnetic Resonance Imaging

JoVE 10393

Source: Frederick W. Damen and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

In this video, high field, small-bore magnetic resonance imaging (MRI) with physiological monitoring is demonstrated to acquire gated cine loops of the murine cardiovascular system. This procedure provides a basis for assessing left-ventricular function, visualizing vascular networks, and quantifying motion of organs due to respiration. Comparable small animal cardiovascular imaging modalities include high-frequency ultrasound and micro-computed tomography (CT); however, each modality is associated with trade-offs that should be considered. While ultrasound does provide high spatial and temporal resolution, imaging artifacts are common. For example, dense tissue (i.e., the sternum and ribs) can limit imaging penetration depth, and hyperechoic signal at the interface between gas and liquid (i.e., pleura surrounding the lungs) can blur contrast in nearby tissue. Micro-CT in contrast does not suffer from as many in-plane artifacts, but does have lower temporal resolution and limited soft-tissue contrast. Furthermore, micro-CT uses X-ray radiation and often requires the use of contrast agents to visualize vasculature, both of which are known to cause side effects at high doses including radiation damage  and renal injury. Cardiovascular MRI provides a nice compromise between these techniques by negating the need for ionizing radiation and providing the user with the ability to image without contrast agents (although contrast agents are often used for MRI).

This data was acquired with a triggering Fast Low Angle SHot (FLASH) MRI sequence that was gated off of the R-peaks in the cardiac cycle and expiratory plateaus in respiration. These physiological events were monitored through subcutaneous electrodes and a pressure-sensitive pillow that was secured against the abdomen. To ensure the mouse was properly warmed, a rectal temperature probe was inserted and used to control the output of a MRI-safe heating fan. Once the animal was inserted into the bore of the MRI scanner and navigation sequences were run to confirm positioning, the gated FLASH imaging planes were prescribed and data acquired. Overall, high field MRI is a powerful research tool that can provide soft tissue contrast for the study of small animal disease models.

Near-infrared Fluorescence Imaging of Abdominal Aortic Aneurysms

JoVE 10394

Source: Arvin H. Soepriatna¹, Kelsey A. Bullens², and Craig J. Goergen¹

¹ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

² Department of Biochemistry, Purdue University, West Lafayette, Indiana

Near-infrared fluorescence (NIRF) imaging is an exciting optical technique that utilizes fluorescent probes to visualize complex biomolecular assemblies in tissues. NIRF imaging has many advantages over conventional imaging methods for noninvasive imaging of diseases. Unlike single photon emission computed tomography (SPECT) and positron emission tomography (PET), NIRF imaging is rapid, high-throughput, and does not involve ionizing radiation. Furthermore, recent developments in engineering target-specific and activatable fluorescent probes provide NIRF with high specificity and sensitivity, making it an attractive modality in studying cancer and cardiovascular disease. The presented procedure is designed to demonstrate the principles behind NIRF imaging and how to conduct in vivo and ex vivo experiments in small animals to study a variety of diseases. The specific example shown here employs an activatable fluorescent probe for matrix metalloproteinase-2 (MMP2) to study its uptake in two different rodent models of abdominal aortic aneurysms (AAAs).

Photoacoustic Tomography to Image Blood and Lipids in the Infrarenal Aorta

JoVE 10395

Source: Gurneet S. Sangha and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

Photoacoustic tomography (PAT) is an emerging biomedical imaging modality that utilizes light generated acoustic waves to obtain compositional information from tissue. PAT can be used to image blood and lipid components, which is useful for a wide variety of applications, including cardiovascular and tumor imaging. Currently used imaging techniques have inherent limitations that restrict their use with researchers and physicians. For example, long acquisition times, high costs, use of harmful contrast, and minimal to high invasiveness are all factors that limit the use of various modalities in the laboratory and clinic. Currently, the only comparable imaging techniques to PAT are emerging optical techniques. But these also have disadvantages, such as limited depth of penetration and the need for exogenous contrast agents. PAT provides meaningful information in a rapid, noninvasive, label-free manner. When coupled with ultrasound, PAT can be used to obtain structural, hemodynamic, and compositional information from tissue, thereby complementing currently used imaging techniques. The advantages of PAT illustrate its capabilities to make an impact in both the preclinical and clinical environment.

Combined SPECT and CT Imaging to Visualize Cardiac Functionality

JoVE 10396

Source: Alycia G. Berman, James A. Schaber, and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

Here we will demonstrate the fundamentals of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging using mice. The technique involves injecting a radionuclide into a mouse, imaging the animal after it is distributed throughout the body, and then reconstructing the produced images to create a volumetric dataset. This can provide information about anatomy, physiology, and metabolism to improve disease diagnosis and monitor its progression.

In terms of collected data, SPECT/CT provides similar information as positron emission tomography (PET)/CT. However, the underlying principles of these two techniques are fundamentally different since PET requires the detection of two gamma photons, which are emitted in opposite directions. In contrast, SPECT imaging directly measures radiation via a gamma camera. As a result, SPECT imaging has lower spatial resolution than PET. However, it is also less expensive because the SPECT radioactive isotopes are more readily available. SPECT/CT imaging provides both noninvasive metabolic and anatomical information that can be useful for a wide variety of applications.

High-frequency Ultrasound Imaging of the Abdominal Aorta

JoVE 10397

Source: Amelia R. Adelsperger, Evan H. Phillips, and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

High-frequency ultrasound systems are used to acquire high resolution images. Here, the use of a state-of-the-art system will be demonstrated to image the morphology and hemodynamics of small pulsatile arteries and veins found in mice and rats. Ultrasound is a relatively inexpensive, portable, and versatile method for the noninvasive assessment of vessels in humans as well as large and small animals. These are several key advantages that ultraound offers compared to other techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and near-infrared fluorescence tomography (NIRF). CT requires ionizing radiation and MRI can be prohibitively expensive and even impractical in some scenarios. NIRF, on the other hand, is limited by the penetration depth of light required to excite the fluorescent contrast agents.

Ultrasound has limitations in terms of imaging depth; however, this may be overcome by sacrificing resolution and using a lower frequency transducer. Abdominal gas and excess body weight can severely diminish image quality. In the first case, the propagation of sound waves is limited, while in the latter case, they are attenuated by overlying tissues, such as fat and connective tissue. As a result, no contrast or faint contrast may be observed. Finally, ultrasound is a highly user-dependent technique, requiring the sonographer to be familiar with anatomy and to be able to work around issues, such as the appearance of imaging artifacts or acoustic interference.

Noninvasive Blood Pressure Measurement Techniques

JoVE 10478

Source: Hamna J. Qureshi and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

Here we will highlight the key similarities and differences of noninvasive blood pressure measurement techniques between humans and rodents and examine the engineering principles that govern blood pressure. The principles that govern current cuff technology to acquire systolic and diastolic pressures will also be discussed.

Commercially available cuffs that connect with mobile devices are typically compact and portable, thereby allowing measurements to be taken virtually anywhere. Noninvasive, portable blood pressure cuffs are especially useful for patients with hypertension and other cardiovascular problems that require careful monitoring and early detection of any changes in blood pressure.

Similarly, noninvasive blood pressure measurement systems are also available for rodents. This technology is used in laboratory settings and is useful for monitoring animal health throughout a study. While radiotelemetry is the gold standard of blood pressure measurement for rodents, this technique is invasive and can lead to animal mortality if done incorrectly. Noninvasive methods, therefore, are convenient for taking measurements in animals as they can provide valuable data without the need for device implantation. A commercially available system will be used to demonstrate how blood pressure can be measured in humans outside of a clinical setting. This technique allows patients to monitor their own blood pressure periodically without having to visit a clinic each time they want these measurements taken.

The methods described here take advantage of blood flow through the tail of the rodent by using pressure sensors and occlusion cuffs. Both mobile blood pressure cuffs for humans and noninvasive tail-cuff methods for rodents take advantage of similar hemodynamic principles to acquire blood pressure measurements that can provide useful data for users, including clinicians, researchers, and patients.

Computational Fluid Dynamics Simulations of Blood Flow in a Cerebral Aneurysm

JoVE 10479

Source: Joseph C. Muskat, Vitaliy L. Rayz, and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

The objective of this video is to describe recent advancements of computational fluid dynamic (CFD) simulations based on patient- or animal-specific vasculature. Here, subject-based vessel segmentations were created, and, using a combination of open-source and commercial tools, a high-resolution numerical solution was determined within a flow model. Numerous studies have demonstrated that the hemodynamic conditions within the vasculature affect the development and progression of atherosclerosis, aneurysms, and other peripheral artery diseases; concomitantly, direct measurements of intraluminal pressure, wall shear stress (WSS), and particle residence time (PRT) are difficult to acquire in vivo.

CFD allow such variables to be assessed non-invasively. In addition, CFD is used to simulate surgical techniques, which provides physicians better foresight regarding post-operative flow conditions. Two methods in magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) with either time of flight (TOF-MRA) or contrast-enhanced MRA (CE-MRA) and phase-contrast (PC-MRI), allow us to obtain vessel geometries and time-resolved 3D velocity fields, respectively. TOF-MRA is based on the suppression of the signal from static tissue by repeated RF pulses that are applied to the imaged volume. A signal is obtained from unsaturated spins moving into the volume with the flowing blood. CE-MRA is a better technique for imaging vessels with complex recirculating flows, as it uses a contrast agent, such as gadolinium, to increase the signal.

Separately, PC-MRI utilizes bipolar gradients to generate phase shifts that are proportional to a fluid's velocity, thus providing time-resolved velocity distributions. While PC-MRI is capable of providing blood flow velocities, the accuracy of this method is affected by limited spatiotemporal resolution and velocity dynamic range. CFD provides superior resolution and can assess the range of velocities from high-speed jets to slow recirculating vortices observed in diseased blood vessels. Thus, even though the reliability of CFD depends on the modeling assumptions, it opens up the possibility for high quality, comprehensive depiction of patient-specific flow fields, which can guide diagnosis and treatment.

Quantitative Strain Mapping of an Abdominal Aortic Aneurysm

JoVE 10480

Source: Hannah L. Cebull¹, Arvin H. Soepriatna¹, John J. Boyle² and Craig J. Goergen¹

¹Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

²Mechanical Engineering & Materials Science, Washington University in St. Louis, St Louis, Missouri

The mechanical behavior of soft tissues, such as blood vessels, skin, tendons, and other organs, are strongly influenced by their composition of elastin and collagen, which provide elasticity and strength. The fiber orientation of these proteins depends on the type of soft tissue and can range from a single preferred direction to intricate meshed networks, which can become altered in diseased tissue. Therefore, soft tissues often behave anisotropically on the cellular and organ level, creating a need for three-dimensional characterization. Developing a method for reliably estimating strain fields within complex biological tissues or structures is important to mechanically characterize and understande disease. Strain represents how soft tissue relatively deforms over time, and it can be described mathematically through various estimations.

Acquiring image data over time allows deformation and strain to be estimated. However, all medical imaging modalities contain some amount of noise, which increases the difficulty of accurately estimating in vivo strain. The technique described here successfully overcomes these issues by using a direct deformation estimation (DDE) method to calculate spatially varying 3D strain fields from volumetric image data.

Current strain estimation methods include digital image correlation (DIC) and digital volume correlation. Unfortunately, DIC can only accurately estimate strain from a 2D plane, severely limiting the application of this method. While useful, 2D methods such as DIC have difficulty quantifying strain in regions that undergo 3D deformation. This is because out-of-plane motion creates deformation errors. Digital volume correlation is a more applicable method that divides the initial volume data into regions and finds the most similar region of the deformed volume, thereby reducing out-of-plane error. However, this method proves to be sensitive to noise and requires assumptions about the mechanical properties of the material.

The technique demonstrated here eliminates these issues by using a DDE method, thus making it very useful in the analysis of medical imaging data. Furthermore, it is robust to high or localized strain. Here we describe the acquisition of gated, volumetric 4D ultrasound data, its conversion into an analyzable format, and the use of a custom Matlab code to estimate 3D deformation and corresponding Green-Lagrange strains, a parameter that better describes large deformations. The Green-Lagrange strain tensor is implemented in many 3D strain estimation methods because it allows for F to be calculated from a Least Squares Fit (LSF) of the displacements. The equation below represents the Green-Lagrange strain tensor, E, where F and I represent the deformation gradient and second order identity tensor, respectively.

(1)