Ultrasonic transducer-guided electrochemical impedance spectroscopy to assess lipid-laden plaques

Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n = 3 for fat-fed, n = 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility (p < 0.0001 for magnitude, p < 0.05 for phase at <15 kHz) as compared to EIS sensor alone (p < 0.07 for impedance, p < 0.4 for phase at <15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque

Ultrasonic transducer-guided electrochemical impedance spectroscopy to assess lipid-laden plaques

Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n = 3 for fat-fed, n = 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility (p < 0.0001 for magnitude, p < 0.05 for phase at <15 kHz) as compared to EIS sensor alone (p < 0.07 for impedance, p < 0.4 for phase at <15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque

Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy

Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI 25 kg/m²). Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome

Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI 25 kg/m²). Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome

Genome-Wide DNA Methylation Patterns of Muscle and Tail-Fat in DairyMeade Sheep and Mongolian Sheep

This study aimed to explore the genome-wide DNA methylation differences between muscle and tail-fat tissues of DairyMeade sheep (thin-tailed, lean carcass) and Mongolian sheep (fat-tailed, fat-deposited carcass). Whole-genome bisulfite sequencing (WGBS) was conducted and the global DNA methylation dynamics were mapped. Generally, CGs had a higher DNA methylation level than CHHs and CHGs, and tail-fat tissues had higher CG methylation levels than muscle tissues. For DNA repeat elements, SINE had the highest methylation level, while Simple had the lowest. When dividing the gene promoter region into small bins (200 bp per bin), the bins near the transcription start site (&plusmn;200 bp) had the highest CG count per bin but the lowest DNA methylation levels. A series of DMRs were identified in muscle and tail-fat tissues between the two breeds. Among them, the introns of gene CAMK2D (calcium/calmodulin-dependent protein kinase II &delta;) demonstrated significant DNA methylation level differences between the two breeds in both muscle and tail-fat tissues, and it may play a crucial role in fat metabolism and meat quality traits. This study may provide basic datasets and references for further epigenetic modification studies during sheep genetic improvement

In-vivo intravascular intervention with parylene micro-electrode to diagnose rupture-prone atherosclerotic plaque using electrical impedance spectroscopy

It is of great clinical interest to have easy and reliable diagnostic techniques to localize and identify vulnerable plaques. Here, an in-vivo, catheter-integrated and balloon-mounted Parylene-C micro electrode impedance sensor was developed for intra-vascular interrogation of atherosclerotic vulnerable plaques using Electrical Impedance spectroscopy (EIS). Successful in vivo experiments of the EIS device were demonstrated using high-fat-dieted New Zealand rabbits. The results showed that electrical impedance spectroscopy (EIS) with micro parylene electrodes is promising to distinguish unstable plaques

In-vivo intravascular intervention with parylene micro-electrode to diagnose rupture-prone atherosclerotic plaque using electrical impedance spectroscopy

It is of great clinical interest to have easy and reliable diagnostic techniques to localize and identify vulnerable plaques. Here, an in-vivo, catheter-integrated and balloon-mounted Parylene-C micro electrode impedance sensor was developed for intra-vascular interrogation of atherosclerotic vulnerable plaques using Electrical Impedance spectroscopy (EIS). Successful in vivo experiments of the EIS device were demonstrated using high-fat-dieted New Zealand rabbits. The results showed that electrical impedance spectroscopy (EIS) with micro parylene electrodes is promising to distinguish unstable plaques

Comparative Transcriptome Analysis Provides Insights into the Polyunsaturated Fatty Acid Synthesis Regulation of Fat-1 Transgenic Sheep

Transgenic technology has huge application potential in agriculture and medical fields, such as producing new livestock varieties with new valuable features and xenotransplantation. However, how an exogenous gene affects the host animal&rsquo;s gene regulation networks and their health status is still poorly understood. In the current study, Fat-1 transgenic sheep were generated, and the tissues from 100-day abnormal (DAF_1) and normal (DAF_2) fetuses, postnatal lambs (DAF_4), transgenic-silencing (DAFG5), and -expressing (DAFG6) skin cells were collected and subjected to transcriptome sequencing, and their gene expression profiles were compared in multiple dimensions. The results were as follows. For DAF_1, its abnormal development was caused by pathogen invasion but not the introduction of the Fat-1 gene. Fat-1 expression down-regulated the genes related to the cell cycle; the NF-&kappa;B signaling pathway and the PI3K/Akt signaling pathway were down-regulated, and the PUFAs (polyunsaturated fatty acids) biosynthesis pathway was shifted toward the biosynthesis of high-level n-3 LC-PUFAs (long-chain PUFAs). Four key node genes, FADS2, PPARA, PRKACA, and ACACA, were found to be responsible for the gene expression profile shift from the Fat-1 transgenic 100-day fetus to postnatal lamb, and FADS2 may play a key role in the accumulation of n-3 LC-PUFAs in Fat-1 transgenic sheep muscle. Our study provides new insights into the FUFAs synthesis regulation in Fat-1 transgenic animals

Whole-genome resequencing of Ujumqin sheep to investigate the determinants of the multi-vertebral trait

The Ujumqin sheep is one of the most profitable breeds in China, with unique multi-vertebral characteristics. We performed high-throughput genome resequencing of five multi-vertebral and three non-multi-vertebral sheep in an Ujumqin population. We identified the genomic regions that correlated with the germplasm characteristics to establish the cause of the “multi-vertebral” phenotype in this breed. Sequencing generated a total of 314.952 G of raw data. The alignment rate of all the samples was between 98.53% and 99.11%, and the mean depth of coverage relative to the reference genome was between 11.58× and 14.92×. After comparing the differences between the two groups, we identified 21 homozygous single nucleotide polymorphisms (SNPs) in the mutant exons of 14 genes. Nineteen loci of 10 genes contained nonsynonymous mutations, while 2 loci contained synonymous mutations. Resequencing revealed homozygous mutations comprised of 44 indels located within exons of 19 genes. These indels included 37 frameshift mutations, 6 non-frameshift mutations, and 1 stopgain single nucleotide variation (SNV). Finally, comparisons of genotypic variations revealed 17 genes with homozygous mutations in their coding regions, 5 of which have previously been associated with vertebral development and the remaining 12 genes were newly identified in this study.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author