Browsing by Author "Goergen, Craig J."
Now showing 1 - 10 of 16
Results Per Page
Sort Options
Item Activation of the Hedgehog signaling pathway leads to fibrosis in aortic valves(BMC, 2023-03-02) Gu, Dongsheng; Soepriatna, Arvin H.; Zhang, Wenjun; Li, Jun; Zhao, Jenny; Zhang, Xiaoli; Shu, Xianhong; Wang, Yongshi; Landis, Benjamin J.; Goergen, Craig J.; Xie, Jingwu; Pediatrics, School of MedicineBackground: Fibrosis is a pathological wound healing process characterized by excessive extracellular matrix deposition, which interferes with normal organ function and contributes to ~ 45% of human mortality. Fibrosis develops in response to chronic injury in nearly all organs, but the a cascade of events leading to fibrosis remains unclear. While hedgehog (Hh) signaling activation has been associated with fibrosis in the lung, kidney, and skin, it is unknown whether hedgehog signaling activation is the cause or the consequence of fibrosis. We hypothesize that activation of hedgehog signaling is sufficient to drive fibrosis in mouse models. Results: In this study, we provide direct evidence to show that activation of Hh signaling via expression of activated smoothened, SmoM2, is sufficient to induce fibrosis in the vasculature and aortic valves. We showed that activated SmoM2 -induced fibrosis is associated with abnormal function of aortic valves and heart. The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves. Conclusions: Our data show that activating hedgehog signaling is sufficient to drive fibrosis in mice, and this mouse model is relevant to human aortic valve stenosis.Item Assessing breast tumor margin by multispectral photoacoustic tomography(Optical Society of America, 2015-03-12) Li, Rui; Wang, Pu; Lan, Lu; Lloyd Jr., Frank P.; Goergen, Craig J.; Chen, Shaoxiong; Cheng, Ji-Xin; Department of Pathology and Laboratory Medicine, IU School of MedicineAn unmet need exists in high-speed and highly-sensitive intraoperative assessment of breast cancer margin during conservation surgical procedures. Here, we demonstrate a multispectral photoacoustic tomography system for breast tumor margin assessment using fat and hemoglobin as contrasts. This system provides ~3 mm tissue depth and ~125 μm axial resolution. The results agreed with the histological findings. A high sensitivity in margin assessment was accomplished, which opens a compelling way to intraoperative margin assessment.Item Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves(Elsevier, 2016-03) Hui, Jie; Li, Rui; Phillips, Evan H.; Goergen, Craig J.; Sturek, Michael; Cheng, Ji-Xin; Department of Cellular & Integrative Physiology, IU School of MedicineThe quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology.Item Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction(MDPI, 2017-03-29) Wodicka, James R.; Chambers, Andrea M.; Sangha, Gurneet S.; Goergen, Craig J.; Panitch, Alyssa; Medicine, School of MedicineEndothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state. Multiple EC-SEAL variants were evaluated and the lead variant was found to preferentially bind to selectin-expressing ECs and smooth muscle cells (SMCs) and inhibit platelet binding and activation in a dose-dependent manner. In an in vivo model of DVT, treatment with the lead variant resulted in reduced thrombus formation. These results indicate that EC-SEAL has promise as a potential therapeutic in the treatment of endothelial dysfunction.Item Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis(Wiley, 2024) Kaefer, Samuel L.; Zhang, Lujuan; Morrison, Rachel A.; Brookes, Sarah; Awonusi, Oluwaseyi; Shay, Elizabeth; Hoilett, Orlando S.; Anderson, Jennifer L.; Goergen, Craig J.; Voytik-Harbin, Sherry; Halum, Stacey; Otolaryngology -- Head and Neck Surgery, School of MedicineObjectives: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. Methods: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. Results: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. Conclusions: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction.Item Functional cardiac consequences of β-adrenergic stress-induced injury in a model of Duchenne muscular dystrophy(The Company of Biologists, 2024) Earl, Conner C.; Javier, Areli J.; Richards, Alyssa M.; Markham, Larry W.; Goergen, Craig J.; Welc, Steven S.; Medicine, School of MedicineCardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD); however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to stimulate injury and enhance cardiac pathology in the mdx model, many methods lead to high mortality with variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. mdx and wild-type mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathological assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes and diminished cardiac reserve in mdx compared to wild-type mice. Our findings highlight the utility of challenging mdx mice with low-dose isoproterenol as a valuable model for exploring therapies targeting DMD-associated cardiac pathologies.Item Functional cardiac consequences of β-adrenergic stress-induced injury in the mdx mouse model of Duchenne muscular dystrophy(bioRxiv, 2024-04-20) Earl, Conner C.; Javier, Areli J.; Richards, Alyssa M.; Markham, Larry W.; Goergen, Craig J.; Welc, Steven S.; Anatomy, Cell Biology and Physiology, School of MedicineCardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to enhance the cardiac phenotype in the mdx model, many methods lead to high mortality, variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. For our study, mdx and wild-type (WT) mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathologic assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels, and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes, and diminished cardiac reserve in mdx mice compared to wild-type. Our findings highlight the utility of low-dose isoproterenol in mdx mice as a valuable model for exploring therapies targeting DMD-associated cardiac complications.Item In Vivo Visualization and Quantification of Rat Laryngeal Blood Supply After Hydration Challenge(Wiley, 2024) Duan, Chenwei; Anderson, Jennifer L.; Schepers, Luke E.; Damen, Frederick W.; Cox, Abigail; Goergen, Craig J.; Sivasankar, Preeti M.; Surgery, School of MedicineObjectives: Systemic dehydration decreases total body blood volume; however, hemodynamic alterations at the level of local organs, such as the larynx, remain unclear. Here we sought to quantify superior thyroid artery (STA) blood flow after dehydration and rehydration using in vivo magnetic resonance angiography (MRA) and ultrasound imaging in a rat model. Methods: Male Sprague-Dawley rats (N = 17) were included in this prospective, repeated measures design. Rats first underwent MRA to determine baseline STA cross-sectional area, followed by high-frequency in vivo ultrasound imaging to measure STA blood velocity at baseline. Next, rats were systemically dehydrated (water withholding), followed by rehydration (water ad-lib). Ultrasound imaging was repeated immediately after dehydration and following rehydration. The STA blood velocity and STA cross-sectional area were used to compute STA blood flow. Three rats served as temporal controls for ultrasound imaging. To determine if the challenges to hydration status affected the STA cross-sectional area, four rats underwent only MRA at baseline, dehydration, and rehydration. Results: Systemic dehydration resulted in 10.5% average body weight loss. Rehydration resulted in average body weight gain of 10.9%. Statistically significant reductions were observed in STA mean blood flow rate after dehydration. Rehydration reversed these changes to pre-dehydration levels. No significant differences were observed in STA cross-sectional area with dehydration or rehydration. Conclusion: Systemic dehydration decreased blood flow in the superior thyroid artery. Rehydration restored blood flow in the STA. Change in hydration status did not alter the STA cross-sectional area. These preliminary findings demonstrate the feasibility of using ultrasound and MRA to quantify hemodynamic changes and visualize laryngeal blood vessels.Item Left atrial reservoir strain as a predictor of cardiac dysfunction in a murine model of pressure overload(Wiley, 2025) Salvas, John P.; Moore-Morris, Thomas; Goergen, Craig J.; Sicard, Pierre; Biomedical Engineering, Purdue School of Engineering and TechnologyAim: Left atrial (LA) strain is emerging as a valuable metric for evaluating cardiac function, particularly under pathological conditions such as pressure overload. This preclinical study investigates the predictive utility of LA strain on cardiac function in a murine model subjected to pressure overload, mimicking pathologies such as hypertension and aortic stenosis. Methods: High-resolution ultrasound was performed in a cohort of mice (n = 16) to evaluate left atrial and left ventricular function at baseline and 2 and 4 weeks after transverse aortic constriction (TAC). Acute adaptations in cardiac function were assessed in a subgroup of mice (n = 10) with 3 days post-TAC imaging. Results: We report an increase in LA max volume from 11.0 ± 4.3 μL at baseline to 26.7 ± 16.7 μL at 4 weeks (p = 0.002) and a decrease in LA reservoir strain from 20.8 ± 5.4% at baseline to 10.2 ± 6.9% at 4 weeks (p = 0.001). In the acute phase, LA strain dysfunction was present at 3 days (p < 0.001), prior to alterations in LA volume (p = 0.856) or left ventricular (LV) ejection fraction (p = 0.120). LA reservoir strain correlated with key indicators of cardiac performance including left ventricular (LV) ejection fraction (r = 0.541, p < 0.001), longitudinal strain (r = -0.637, p < 0.001), and strain rate (r = 0.378, p = 0.007). Furthermore, markers of atrial structure and function including LA max volume (AUC = 0.813, p = 0.003), ejection fraction (AUC = 0.853, p = 0.001), and strain (AUC = 0.884, p < 0.001) all predicted LV dysfunction. Conclusion: LA strain and function assessments provide a reliable, non-invasive method for the early detection and prediction of cardiac dysfunction in a model of pressure overload.Item Murine Ultrasound-Guided Transabdominal Para-Aortic Injections of Self-Assembling Type I Collagen Oligomers(Elsevier, 2017-03-10) Yrineo, Alexa A.; Adelsperger, Amelia R.; Durkes, Abigail C.; Distasi, Matthew R.; Voytik-Harbin, Sherry L.; Murphy, Michael P.; Goergen, Craig J.; Surgery, School of MedicineAbdominal aortic aneurysms (AAAs) represent a potentially life-threatening condition that predominantly affects the infrarenal aorta. Several preclinical murine models that mimic the human condition have been developed and are now widely used to investigate AAA pathogenesis. Cell- or pharmaceutical-based therapeutics designed to prevent AAA expansion are currently being evaluated with these animal models, but more minimally invasive strategies for delivery could improve their clinical translation. The purpose of this study was to investigate the use of self-assembling type I collagen oligomers as an injectable therapeutic delivery vehicle in mice. Here we show 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 at body temperature. A commonly used infrarenal mouse AAA model was used to determine the target location of these collagen injections. Ultrasound-guided, closed-abdominal injections supported consistent delivery of collagen to the area surrounding the infrarenal abdominal aorta halfway between the right renal artery and aortic trifurcation into the iliac and tail arteries. This minimally invasive approach yielded outcomes similar to open-abdominal injections into the same region. Histological analysis on tissue removed on day 14 post-operatively 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. Finally, we showed that the typical length and position of this infrarenal AAA model was statistically similar to the length and targeted location of the injected collagen, increasing its feasibility as a localized therapeutic delivery vehicle. Future preclinical and clinical studies are needed to determine if specific therapeutics incorporated into the self-assembling type I collagen matrix described here can be delivered near the aorta and locally limit AAA expansion.,