<p>Vocal fold vibration results in voice production. Optimal hydration levels contribute to self-sustained vocal fold vibration and preservation of voice quality. Adequate hydration is implicated as a factor in maintaining voice and preventing voice problems. Voice problems affect up to one third of adults during their lifetime. But whether altered hydration state adversely affects vocal fold biology and biomechanics is still unclear. To untangle the effects of systemic dehydration on vocal fold biology, we developed a water restriction protocol on lab animals that can translate to humans. Our results showed that dehydration induced by restricted water access downregulated the gene expression of IL-1α and desmoglein-1, upregulated the gene expression level of hyaluronidase-2, and downregulated hyaluronic acid (HA).</p> <p>Clinically, hydration treatments are hypothesized to maintain the viscoelastic properties of vocal folds. However, our understanding of the relationship between vocal fold tissue hydration level and biomechanical properties is still evolving. To investigate the effects of dehydration on biomechanical properties we used an ex vivo experimental design. We hypothesized that the optimal stiffness of vocal folds would be impacted after dehydration via losing both water and HA, but that the stiffness properties would recover through rehydration. To test this hypothesis, we experimentally treated porcine vocal fold samples using two different approaches: 1) immersion in hypertonic solution (15% NaCl in ddH2O) and PBS sequentially to mimic dehydration and rehydration, and 2) incubation with hyaluronidase (Hyal) to mimic HA loss during dehydration. Our results showed that loss of water increased tissue stiffness and could be recovered through rehydration in a certain degree. In addition, loss of HA increased tissue stiffness. </p> <p>In While dehydration decreases total body blood volume, different tissues and organs of the body may be impacted in different ways from dehydration. Therefore, it is important to investigate the hemodynamic alterations during changes to hydration status. Magnetic resonance angiography (MRA) and ultrasound imaging were employed to identify the delicate vascular geometry and hemodynamics of the laryngeal blood supply. Animals underwent both MRA and ultrasound imaging at baseline, dehydration and rehydration time points. Our results showed that dehydration impacted the blood supply to larynx. This blood supply was restored through rehydration treatment.</p> <p>Overall, this research has been successful in establishing a mild dehydration animal model, providing evidence from gene and protein levels that dehydration affects cytokine production and extracellular matrix components (ECM) in vocal fold, demonstrating the vocal fold tissue biomechanical behavior after dehydration and loss of HA, and offering a combination application of MRA and ultrasound imaging to study vascular geometry and hemodynamics of the blood supply to the vocal fold region.</p>

<p>Preeclampsia and other hypertensive disorders of pregnancy impact 2-8% of pregnancies with often devastating results. Current treatment methods resort to birth, which forces the fetus into the world before they are fully developed but can save the mother’s life. Preeclampsia is broadly considered to be of placental origin and current etiologic understanding focuses on systemic endothelial dysfunction triggered by an imbalance of vasoregulatory factors released by this maternal/fetal organ. This imbalance explains many early-term cases but fails to adequately address later cases where this imbalance is not always seen. Conversely, ischemia-reperfusion of the kidney is known to correlate with endothelial dysfunction, and preeclamptic women are known to have a stenosis in their left renal vein (LRV) in the supine position (on their back). Herein, we suggest that extrinsic compression of the LRV by the gravid uterus, without collaterals, produces a renal injury which can induce systemic endothelial cell dysfunction. We theorize this compression is position dependent and produces renal ischemia through an unchecked cycle of increased intrarenal pressure, subsequent afferent arteriole constriction and decreased glomerular perfusion, and activation of the renin-angiotensin-aldosterone system. We aim to elucidate this through murine studies of a surgically induced LRV stenosis and a retrospective clinical study where the maternal renal veins are measured from magnetic resonance images. Findings from this work suggest partial renal venous outflow obstruction leads to renal injury but could be moderated through alternative maternal resting positions. This potential alternative pathologic mechanism has significant clinical implications for future therapies targeting this condition.</p>

The stomach is a digestive organ in the gastrointestinal tract that regulates food intake and paces digestion of nutrients and fluids. The emptying and motility patterns of the stomach are crucial rate-determining processes in maintaining energy homeostasis in the body. Dysregulation of gastric functions often leads to distressing conditions such as gastroesophageal reflux diseases, functional dyspepsia, gastroparesis and obesity. Gastric disorders affect more than 60 million people in the US, producing significant medical and economic burden. These diseases are often chronic and greatly compromise quality of life. As the causes of these diseases remain largely unknown, effects of current pharmacological, dietary, or surgical treatments are often dismal. In this regard, neuromodulation of peripheral nerves emerges as a promising electroceutical therapy for remedying gastric disorders. However, therapeutic effects were shown to be modest, largely due to the inability to validate or calibrate the efficacy and stability of neuromodulation methods with appropriate physiological readouts. To address these problems, here I developed a non-invasive, repeatable online high-resolution magnetic resonance imaging protocol, empowered with advanced image processing algorithms, to track gastric emptying, antral motility, pyloric motility, intestinal filling and absorption in a rat model. The protocol can be used to guide tuning and optimization of stimulation parameters of neuromodulation without perturbing ongoing and spontaneous physiology. The proposed technology and findings are expected to pave the way for the use of gastric MRI to evaluate the efficacy of therapeutics in treating gastric disorders under both preclinical and clinical settings.

<p>Lipids and sodium (²³Na) are two essential components of the human body. They play a role in almost all biological systems. However, an increase in their levels is associated with metabolic diseases. The elevation of their contents can cause similar health disorders. Examples of prevalent disorders that share an increase of musculoskeletal lipids and ²³Na are hypertension and diabetes. However, the relationship between in vivo lipid and sodium levels in pathophysiology has not been studied enough and therefore is still unclear. Additionally, the available quantification methods to facilitate such a study may not be practical. They are either invasive, not sensitive enough, or require an impractical measurement time.</p> <p>Therefore, in this work, our aims were to develop practical in vivo methods to quantify the absolute sodium concentration as well as the concentration of each lipid component individually, and to study the correlation between them within the skeletal muscles.</p> <p>Since lipids and ²³Na have different nuclear magnetic resonance properties, their quantification by magnetic resonance (MR) techniques face different challenges. Thus, we optimized different MR spectroscopic imaging (MRSI) techniques for lipids and ²³Na. </p> <p>Our proposed proton MRSI was able to provide eight lipid fat fraction (FF) maps representing each musculoskeletal lipid component (fatty acid) detected by our MRSI technique, and demonstrated a superior sensitivity compared to the conventional MR imaging methods.</p> <p>For ²³Na, our developed ²³Na-MRSI was able to measure and map the absolute ²³Na concentration with values agreeing with those reported previously in biopsy studies, and with a high repeatability (CV < 6 %) within significantly shorter acquisition time compared to other available techniques.</p> <p> Finally, the ²³Na concentration and the fat fractions of each lipid component within healthy skeletal muscles were measured and correlated using our developed MRSI methods. Our findings suggest a positive regional relationship between ²³Na and lipids and negative correlation between ²³Na and BMI under healthy conditions.</p>

<p>Herein, the development, optimization, and evaluation of quantitative techniques are presented for dynamic PET studies in cancer imaging applications. Dynamic PET image analysis techniques are first applied to 18F-fluoroethyltyrosine (FET) PET imaging of glioma and brain metastasis patients. In a second application, dynamic PET image analysis techniques are applied to 68Ga-PSMA-11 PET imaging for primary prostate cancer patients. Overall, the application of dynamic PET imaging techniques supports improved clinical outcomes and enhanced clinician confidence for treatment modifications. </p>

In recent years, development of various imaging, recording and stimulation tools are rapidly advancing our knowledge of the human anatomy and its underlying interconnections. As a truly non-invasive tool, Magnetic Resonance Imaging (MRI), is creating new opportunities to understand large scale biological processes with a fine detail. Furthermore, novel materials and microfabrication techniques are allowing researchers to develop tools that record bio-signal or modulate complex physiology with high temporal precision. However, these tools, when used individually can elucidate only a partial view of the human body and the brain. There is a growing need in both the research and clinical community to find ways to perform these modalities together and visualize biological systems across a vast range of spatiotemporal scale. However, severe methodological challenges act as bottlenecks for any such multimodal integration.<br><div><br></div><div>To address this critical need, I have designed an MRI-safe platform for high-fidelity bio-signal recording and electrical stimulation during concurrent MRI imaging. Central to this system are novel miniaturized microelectronic devices, that operate wirelessly in synchrony with MRI scans. The system leverages surplus functionalities of a conventional scanner to integrate with the imaging system and provide a simple and inexpensive solution towards multimodal imaging. This work also describes a systematic approach for development and evaluation of this plug-and-play system through in-vivo experiments in animal models. The clinical relevance of the multimodal imaging platform was further showcased through a study on the mechanism of SUDEP (Sudden death in epilepsy), a terminal complication associated with epilepsy. With future refinements, I expect this platform will provide affordable, accessible, and reliable solutions for multimodal imaging in animals and humans, creating unique opportunities for basic scientific research and clinical diagnosis.<br></div>