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Research


Dr. Craig J. Goergen joined the Weldon School at Purdue University as an Assistant Professor of Biomedical Engineering in December of 2012. With his training in bioengineering, imaging research background, and industry experience in one of the largest biotechnology companies in the world (Genentech Inc.), Dr. Goergen and his group are uniquely positioned to identify and address clinical needs related to medical imaging and diagnostics. The mission of the Cardiovascular Imaging Research Laboratory (CVIRL) is to advance imaging techniques for the study of disease progression, ultimately enhancing the clinical care of patients and improving quality of life. The original focus of the CVIRL was to develop imaging techniques to study both cardiac and vascular disease, but current efforts take a more expansive approach, including research projects ranging from cancer to diabetes. Furthering his research potential through connections with key clinical collaborators, Dr. Goergen is also an Adjunct Assistant Professor of Surgery in the Indiana University School of Medicine. The research led by Dr. Goergen in the CVIRL embodies the breadth and depth required to significantly advance the field of biomedical imaging. Three of his group’s major research efforts are summarized below.

 

1) Abdominal Aortic Aneurysm Imaging and Pathology

Dr. Goergen has been studying abdominal aortic aneurysms for more than a decade. His work has revealed that aortic pulsatility is constant across species [1], MRI can be used to quantify aortic curvature and strain [2], and angiotensin II (AngII) infusion in apolipoprotein E-deficient (apoE-/-) leads to leftward expanding suprarenal aortic dissections [3]. These efforts have been cited in several important review articles by other experts in the field [4, 5, 6, 7, 8]. Then in a 2015 study, his group used two established experimental AAA models in an article published in the “Animal Models of Human Pathology” issue of BioMed Research International [9]. The elastase perfusion model leads to fusiform AAAs with focally degraded elastin, while AngII infusion causes spontaneous dissecting AAAs with true and false lumens. High frequency ultrasound revealed volumetric growth, reduced circumferential strain, and altered blood flow dynamics in both models. 

Other studies from his group have shown that AngII infusion does not cause abdominal aortic aneurysms in apoE-/- rats [10] and statistical models can be used to predict development and growth trends in AngII-induced murine dissecting aneurysms [11]. These results suggested that morphological, biomechanical, and hemodynamic characteristics evolve differently for each model [12and, as noted in a review article by Daugherty and colleagues from the Univ. of Kentucky, may help explain the difference in AAA locations “between mice and humans in aneurysm-prone areas of the aorta” [6].

A more recent IEEE Transactions on Medical Imaging article titled “Multi-Modality Imaging Enables Detailed Hemodynamic Simulations in Dissecting Aneurysms in Mice” was published in 2017 (Fig. 1, [13]). This work was performed in collaboration with Dr. Jay Humphrey of Yale and included the first detailed 3D reconstructions of true and false lumens within murine aortic dissections [13]. These were used for computational hemodynamic models that were informed by mouse-specific inlet flows and optimized RCR-Windkessel outlets. The analyses suggested that 1) a false lumen cavity is necessary for the formation of major recirculating events, 2) vortices initially form at the proximal end of the false lumen opening, and 3) differences in morphology and hemodynamics play crucial roles in determining the evolution of dissecting abdominal aortic aneurysms. This coupled high-resolution in vivo and in vitro imaging approach provides much-improved geometric models for hemodynamic simulations, and our imaging-based computational findings suggest a link between perturbations in hemodynamic metrics and aneurysmal disease heterogeneity [14].

Dr. Goergen expanded his AAA work through a 2017 study published in the Journal of Controlled Release that explored innovative therapeutic approaches [15]. Here Dr. Goergen and colleagues described the use of self-assembling type I collagen oligomers as an injectable therapeutic drug, nanoparticle, or cell delivery vehicle in mice. More specifically, his group evaluated the success and reliability of a para-aortic, ultrasound-guided technique for injecting quickly polymerizing collagen oligomer solutions into mice to form a collagen-fibril matrix (Fig. 2; [6, 15]). Histological analysis of tissue removed after 14 days showed minimal in vivo degradation of the self-assembled fibrillar collagen and the majority of implants experienced minimal inflammation and cell invasion, further confirming this material's potential as a method for delivering therapeutics. This work opens the possibility of using self-assembling type I collagen matrix to locally limit AAA expansion.

 

2) 4D Ultrasound Imaging of Cardiac Function

Expanding his expertise in vascular imaging, Dr. Goergen has contributed to the field of small animal cardiac imaging [16, 17, 18, 19]. Recent work by his laboratory showcased the development of a novel 4-dimensional ultrasound (4DUS) imaging strategy for evaluating murine cardiac function (Fig. 3; [20, 21]). Although conventional short-axis motion-mode (SAX MM) ultrasound and cine MRI are two of the most prevalent strategies used for quantifying cardiac function, standard ultrasound is limited by substantial geometric assumptions and MRI requires large and costly systems with substantial infrastructure requirements. Dr. Goergen’s group developed a novel automated 4DUS technique that provides comparable information to cine MRI through spatiotemporally synced imaging of cardiac motion. Cardiac function metrics showed close agreement between cine MRI and 4DUS but overestimations by SAX MM. The inclusion of a mouse model of cardiac hypertrophy [20] or infarction [21] further highlights the precision of 4DUS compared with that of SAX MM. This work was highlighted as a VisualSonics “Featured Publication” as it demonstrates that 4DUS can be used as a reliable technique for longitudinal evaluations of murine cardiac function.

 

3) Label-Free Photoacoustic Imaging

Finally, Dr. Goergen combined his expertise in ultrasound and optical imaging to develop novel optoacoustic techniques that offer great promise for a variety of clinical applications [22, 23]. His group has worked with collaborators to publish on breast tumor margin detection [24] and peripheral nerve visualization [25]. These efforts have been cited in multiple reviews [26, 27, 28, 29] and described by Cheng and Xie in a Science review article as part of a group of work that is pushing the “boundary of the vibrational spectroscopic imaging field in terms of acquisition speed, detection sensitivity, spatial resolution, and imaging depth” [30]. Then in 2017, a Biomedical Optics Express article titled “In Vivo Photoacoustic Lipid Imaging in Mice Using the Second Near-Infrared Window” was published that describes Dr. Goergen’s innovative work developing photoacoustic imaging for noninvasive, label-free study of vascular disease [31]. This is especially applicable to lipid-based diseases, responsible for a significant portion of world mortality via diabetes, obesity, liver disease and vascular diseases. This paper is the first report an in vivo ultrasound/photoacoustic modality that is capable of noninvasively providing label-free optical contrast of both lipid and blood in small animals (Fig. 4 [31]). The acquired lipid signals suggested that older hyperlipidemic male mice have greater periaortic fat accumulation compared to adolescent males, females, and wildtype controls. More recent work is focused on developing an adjustable photoacoustic holder capable of improved penetration depth via adjustable optical fiber holders controlled by bipolar stepper motors [32]. These results demonstrate the ability of photoacoustic tomography to quantify biological changes that are relevant in vascular pathophysiology and also highlight its potential to improve the diagnosis of lipid-based diseases [33].

 

The publications highlighted above are but a small snapshot of the work currently underway in the CVIRL. As Principal Investigator, Dr. Goergen is working with a talented group of researchers who can identify a clinical need, develop a strategy to tackle the problem, and then have the wherewithal to implement a solution. Dr. Goergen is the recipient of the 2017 BMES Rita Schaffer Young Investigator Award and is highly regarded by his collaborators as a go-to person for innovative and practical solutions. With continued efforts, the CVIRL is working to eventually make a positive impact on the clinical care of patients.