Hoyt, Kenneth
Permanent URI for this collectionhttps://hdl.handle.net/10735.1/5911
Kenneth Hoyt is an Associate Professor in the Department of Bioengineering. He also holds a joint faculty appointment at UT Southwestern Medical Center. At UT Dallas he runs the Ultrasound Imaging and Therapy Laboratory. His research interests include:
- Cancer
- Medical imaging
- Signal and image processing
- Ultrasound
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Recent Submissions
Item Morphological Image Processing for Multiscale Analysis of Super-Resolution Ultrasound Images of Tissue Microvascular Networks(SPIE-Int Soc Optical Engineering, 2019-03-15) Özdemir, Ipek; Hoyt, Kenneth; Özdemir, Ipek; Hoyt, KennethDiabetes is a major disease and known to impair microvascular recruitment due to insulin resistance. Previous quantifications of the changes in microvascular networks at the capillary level were being performed with either full or manually selected region-of-interests (ROIs) from super-resolution ultrasound (SR-US) images. However, these approaches were imprecise, time-consuming, and unsuitable for automated processes. Here we provided a custom software solution for automated multiscale analysis of SR-US images of tissue microvascularity patterns. An Acuson Sequoia 512 ultrasound (US) scanner equipped with a 15L8-S linear array transducer was used in a nonlinear imaging mode to collect all data. C57BL/6J male mice fed standard chow and studied at age 13-16 wk comprised the lean group (N = 14), and 24-31 wk-old mice who received a high-fat diet provided the obese group (N = 8). After administration of a microbubble (MB) contrast agent, the proximal hindlimb adductor muscle of each animal was imaged (dynamic contrast-enhanced US, DCE-US) for 10 min at baseline and again at 1 h and towards the end of a 2 h hyperinsulinemic-euglycemic clamp. Vascular structures were enhanced with a multiscale vessel enhancement filter and binary vessel segments were delineated using Otsu's global threshold method. We then computed vessel diameters by employing morphological image processing methods for quantitative analysis. Our custom software enabled automated multiscale image examination by defining a diameter threshold to limit the analysis at the capillary level. Longitudinal changes in AUC, I_{PK}, and MVD were significant for lean group (p < 0.02 using Full-ROI and p < 0.01 using 150 μm-ROI) and for obese group (p < 0.02 using Full-ROI, p < 0.03 using 150 μm-ROI). By eliminating large vessels from the ROI (above 150 μm in diameter), perfusion parameters were more sensitive to changes exhibited by the smaller vessels, that are known to be more impacted by disease and treatment.Item Deep 3D Convolutional Neural Networks for Fast Super-Resolution Ultrasound Imaging(SPIE, 2019-03-15) Brown, Katherine; Dormer, James; Fei, Baowei; Hoyt, Kenneth; Brown, Katherine; Dormer, James; Fei, Baowei; Hoyt, KennethSuper-resolution ultrasound imaging (SR-US) is a new technique which breaks the diffraction limit and can help visualize microvascularity at a resolution of tens of microns. However, image processing methods for spatiotemporal filtering needed in SR-US for microvascular delineation, such as singular value decomposition (SVD), are computationally burdensome and must be performed off-line. The goal of this study was to evaluate a novel and fast method for spatiotemporal filtering to segment the microbubble (MB) contrast agent from the tissue signal with a trained 3D convolutional neural network (3DCNN). In vitro data was collected using a programmable ultrasound (US) imaging system (Vantage 256, Verasonics Inc, Kirkland, WA) equipped with an L11-4v linear array transducer and obtained from a tissue-mimicking vascular flow phantom at flow rates representative of microvascular conditions. SVD was used to detect MBs and label the data for training. Network performance was validated with a leave-one-out approach. The 3DCNN demonstrated a 22% higher sensitivity in MB detection than SVD on in vitro data. Further, in vivo 3DCNN results from a cancer-bearing murine model revealed a high level of detail in the SR-US image demonstrating the potential for transfer learning from a neural network trained with in vitro data. The preliminary performance of segmentation with the 3DCNN was encouraging for real-time SR-US imaging with computation time as low as 5 ms per frame.Item Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics(Springer, 2018-10-08) Patnaik, Sourav S.; Simionescu, Dan T.; Goergen, Craig J.; Hoyt, Kenneth; Sirsi, Shashank; Finol, Ender A.; Hoyt, Kenneth; Sirsi, ShashankPentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.Item Impact of Hydrostatic Pressure on Phase-Change Contrast Agent Activation by Pulsed Ultrasound(Acoustical Society of America, 2019-06-14) Raut, Saurabh; Khairalseed, Mawia; Honari, Arvin; Sirsi, Shashank R.; Hoyt, Kenneth; Raut, Saurabh; Khairalseed, Mawia; Honari, Arvin; Sirsi, Shashank R.; Hoyt, KennethA phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration. © 2019 Acoustical Society of America.Item Monitoring Early Breast Cancer Response To Neoadjuvant Therapy Using H-Scan Ultrasound Imaging: Preliminary Preclinical Results(John Wiley and Sons Ltd., 2019-04-17) Khairalseed, Mawia; Javed, Kulsoom; Jashkaran, G.; Kim, J. -W; Parker, K. J.; Hoyt, Kenneth; Hoyt, Kenneth; Khairalseed, Mawia; Javed, KulsoomObjective—H-scan imaging is a new ultrasound technique used to visualize the relative size of acoustic scatterers. The purpose of this study was to evaluate the use of H-scan ultrasound imaging for monitoring early tumor response to neoadjuvant treatment using a preclinical breast cancer animal model. Methods—Real-time H-scan ultrasound imaging was implemented on a programmable ultrasound scanner (Vantage 256; Verasonics Inc., Kirkland, WA) equipped with an L11-4v transducer. Bioluminescence and H-scan ultrasound was used to image luciferase-positive breast cancer–bearing mice at baseline and at 24, 48, and 168 hours after administration of a single dose of neoadjuvant (paclitaxel) or sham treatment. Animals were euthanized at 48 or 168 hours, and tumors underwent histologic processing to identify cancer cell proliferation and apoptosis. Results—Baseline H-scan ultrasound images of control and therapy group tumors were comparable, but the latter exhibited significant changes over the 7-day study (P 0.40, P < .04). Conclusion—Preliminary preclinical results suggest that H-scan ultrasound imaging is a new and promising tissue characterization modality. H-scan ultrasound imaging may provide prognostic value when monitoring early tumor response to neoadjuvant treatment. © 2018 by the American Institute of Ultrasound in Medicine.Item Hyposialylated IgG Activates Endothelial IgG Receptor FcγRIIB to Promote Obesity-Induced Insulin Resistance(American Society for Clinical Investigation, 2018-11-05) Tanigaki, K.; Sacharidou, A.; Peng, J.; Chambliss, K. L.; Yuhanna, I. S.; Ghosh, Debabrata; Ahmed, M.; Szalai, A. J.; Vongpatanasin, W.; Mattrey, R. F.; Chen, Q.; Azadi, P.; Lingvay, I.; Botto, M.; Holland, W. L.; Kohler, J. J.; Sirsi, Shashank R.; Hoyt, Kenneth; Shaul, P. W.; Mineo, C.; Ghosh, Debabrata; Sirsi, Shashank R.; Hoyt, KennethType 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we have shown that activation of the IgG receptor FcγRIIB in endothelium by hyposialylated IgG plays an important role in obesity-induced insulin resistance. Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or selectively in endothelium were protected from insulin resistance as a result of the preservation of insulin delivery to skeletal muscle and resulting maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin resistance. Moreover, IgG transferred from patients with T2DM but not from metabolically healthy subjects caused insulin resistance in IgG-deficient mice via FcγRIIB, indicating that similar processes may be operative in T2DM in humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice impaired endothelial cell insulin transcytosis in culture and in vivo. These effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. Thus, IgG sialylation and endothelial FcγRIIB may represent promising therapeutic targets to sever the link between obesity and T2DM.Item Spatial Angular Compounding Technique for H-Scan Ultrasound Imaging.(2018-10-22) Khairalseed, Mawia; Xiong, Fangyuan; Kim, Jung-whan; Mattrey, Robert F.; Parker, Kevin J.; Hoyt, Kenneth; Khairalseed, Mawia; Xiong, Fangyuan; Kim, Jung-whan; Hoyt, KennethH-Scan is a new ultrasound imaging technique that relies on matching a model of pulse-echo formation to the mathematics of a class of Gaussian-weighted Hermite polynomials. This technique may be beneficial in the measurement of relative scatterer sizes and in cancer therapy, particularly for early response to drug treatment. Because current H-scan techniques use focused ultrasound data acquisitions, spatial resolution degrades away from the focal region and inherently affects relative scatterer size estimation. Although the resolution of ultrasound plane wave imaging can be inferior to that of traditional focused ultrasound approaches, the former exhibits a homogeneous spatial resolution throughout the image plane. The purpose of this study was to implement H-scan using plane wave imaging and investigate the impact of spatial angular compounding on H-scan image quality. Parallel convolution filters using two different Gaussian-weighted Hermite polynomials that describe ultrasound scattering events are applied to the radiofrequency data. The H-scan processing is done on each radiofrequency image plane before averaging to get the angular compounded image. The relative strength from each convolution is color-coded to represent relative scatterer size. Given results from a series of phantom materials, H-scan imaging with spatial angular compounding more accurately reflects the true scatterer size caused by reductions in the system point spread function and improved signal-to-noise ratio. Preliminary in vivo H-scan imaging of tumor-bearing animals suggests this modality may be useful for monitoring early response to chemotherapeutic treatment. Overall, H-scan imaging using ultrasound plane waves and spatial angular compounding is a promising approach for visualizing the relative size and distribution of acoustic scattering sources.Item Novel Method for the Formation of Monodisperse Superheated Perfluorocarbon Nanodroplets as Activatable Ultrasound Contrast Agents(Royal Society of Chemistry, 2018-08-20) De, Gracia Lux; Vezeridis, A. M.; Lux, J.; Armstrong, A. M.; Sirsi, Shashank R.; Hoyt, Kenneth; Mattrey, R. F.; Sirsi, Shashank R.; Hoyt, KennethMicrobubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>10¹² vs. >10¹⁰ NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were sufficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.