Amplitude-Modulation Frequency Optimization for Enhancing Harmonic Motion Imaging Performance of Breast Tumors in the Clinic.

OBJECTIVE: Elastography images tissue mechanical responses and infers the underlying properties to aid diagnosis and treatment response monitoring. The estimation of absolute or relative tumor properties may vary with dimensions even when the mechanical properties remain constant. Harmonic motion imaging (HMI) uses amplitude-modulated (AM) focused ultrasound to interrogate the targeted tissue's viscoelastic properties. In this study, effects of AM frequencies on HMI were investigated in terms of inclusion relative stiffness and size estimation. METHODS: AM frequencies from 200 to 600 Hz in steps of 100 Hz were considered using a 5.3-kPa phantom with cylindrical inclusions (Young's modulus: 22, 31, 44, 56 kPa, and diameter: 4.8, 8.1, 13.6, 19.8 mm) to optimize the performance of HMI in characterizing tumors with the same mechanical properties and of different dimensions. RESULTS: Consistent displacement ratios (DRs) (17.5% variation) of the inclusion to background were obtained with 200-Hz AM for breast-tumor-mimicking inclusions albeit a suboptimal inclusion size estimation obtained. 400-Hz was otherwise used for small and low-contrast inclusions (4.8 mm, 22 or 31 kPa). A linear relationship (R2 = 0.9043) was found between the inverse DR at these frequencies and the Young's modulus ratio. 400 Hz obtained the most accurate inclusion size estimation with an overall estimation error on the lateral dimension of 0.5 mm. In vivo imaging of breast cancer patients (n = 5) was performed at 200 or 400 Hz. CONCLUSION: The results presented herein indicate that the HMI AM frequency could be optimized adaptively in cases of different applications, i.e., at 200 or 400 Hz, depending on whether aimed for consistent DR measurement for tumor response assessment or tumor margin delineation for surgical planning. HMI may thus be capable of predicting the pathologic endpoint of tumors in response to neoadjuvant chemotherapy (NACT) as early as 3 weeks into treatment.

Multi-drug resistant (MDR) Gram-negative pathogenic bacteria isolated from poultry in the Noakhali region of Bangladesh.

Rapidly increasing antibiotic-resistant bacterial strains in Bangladesh's food and farm animals stem from the excessive and inappropriate use of antibiotics. To assess the prevalence of multi-drug resistant (MDR) Gram-negative bacteria in poultry chicks, we sought to isolate and identify strains carrying antimicrobial resistance genes. Isolation and identification involved biochemical tests, 16S rRNA sequencing, and PCR screening of species-specific genes. MDR patterns were evaluated using CLSI guidelines with seventeen antibiotics across twelve classes. Targeted gene sequences were amplified for the detection of Extended-spectrum ß-Lactamase (ESBL), carbapenem, tetracycline, sulfonamide, and colistin resistance genes. Common isolates, such as Escherichia coli, Klebsiella pneumoniae, Proteus penneri, and Enterobacter hormaechei, exhibited average Multiple Antimicrobial Resistance (MAR) indices of 0.66, 0.76, 0.8, 0.84, and 0.81, 0.76, 0.84, 0.41 for broiler and layer chicken, respectively. Providencia stuartii and Salmonella enterica, exclusive to broiler samples, had MAR indices of 0.82 and 0.84, respectively. Additional isolates Morganella morganii, Aeromonas spp., and Wohlfahrtiimonas chitiniclastica were found in layers (Average MAR indices: 0.73, 0.71, and 0.91). Notably, M. morganii, E. hormaechei and W. chitiniclastica were identified for the first time in Bangladeshi poultry chicken, although their evolution is yet to be understood. In this study, Pan-drug resistance was observed in one P. stuartii (broiler) and one Aeromonas spp. (layer) with a MAR index 1, while all isolates exhibited MAR indices >0.2, indicating MDR. Antimicrobial resistance (AMR) gene screening identified blaTEM, blaSHV, tetA, and sul1 in a majority of the MDR strains. Interestingly, E. coli (lactose positive and negative) and E. hormaechei were exclusively found to possess the tetB gene. In addition, E. coli (lactose negative), Klebsiella pneumoniae, Enterobacter hormaechei, M. morganii, and P. stuartii were observed to carry the colistin-resistant mcr-1 gene, whereas sul2 was detected in E. coli (lactose positive and negative), E. hormaechei, P. stuartii, and P. penneri. These findings emphasize the health risk of our consumers of both broiler and layer chickens as they have turned into a potent reservoir of various AMR gene carrying MDR and Pan-drug resistant bacteria.

Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Differences in Associated Factors of Underweight and Overweight According to Rural-Urban Residence Strata among Ever-Married Non-Pregnant Women of Reproductive Age in Bangladesh.

Background: This study sought to compare the prevalence of underweight and overweight among ever-married, non-pregnant women of reproductive age in Bangladesh by urban or rural residency status. Methods: This study used Bangladesh Demographic and Health Survey (BDHS), 2017 data. Cross-sectional study design with two-stage stratified sampling method was employed. A sample of ever-married non-pregnant women of reproductive age was selected and multinomial logistic regression was utilised in analysis. Results: It was found that around half of rural women (45.0%, N = 4,934) and more than half of urban women (60.3%, n = 3,913) were overweight. Nearly one in seven rural women (14.0%, n = 1,537) and 1 in 12 urban women (9.0%, n = 564) were reported as underweight. Our analyses revealed that being overweight was substantially connected with age, husband's occupation, economic status, television access, and division for both urban and rural areas. Women from poor households were significantly more likely to be underweight than women from middle- income households for both urban (P < 0.05; OR: 1.41; 95% CI: 1.03, 1.94) and rural (P < 0.05; OR: 1.23; 95% CI: 1.04, 1.46) areas. Interestingly, women without television access both in urban (P < 0.001; OR = 0.78; 95% CI: 0.67, 0.91) and rural (P < 0.001; OR = 0.75; 95% CI: 0.68, 0.84) areas had an inverse association with overweight/obesity compared to women with television access. In both areas, women in Sylhet and Mymensingh had higher likelihood of being underweight than Barisal division. Additionally, in both residential zones, women in Sylhet had lower likelihood of being overweight than Barisal division. Conclusion: This study reveals that multiple characteristics are linked to both overweight and underweight among ever-married, non-pregnant women of reproductive age in Bangladesh. Addressing these variables should be a priority in public health efforts to combat the dual challenge of malnutrition in Bangladesh.

Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update.

The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS and fUS revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We saw a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with the brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV response with peak CBV, activated area, and correlation coefficient increasing with ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalizes and linearly correlates with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths and the evoked hemodynamic responses colocalized and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as an understanding of how FUS displaces brain tissue and affects cerebral hemodynamics.

Feasibility of Phase Velocity Imaging Using Multi Frequency Oscillation-Shear Wave Elastography.

OBJECTIVE: To assess viscoelasticity, a pathologically relevant biomarker, shear wave elastography (SWE) generally uses phase velocity (PV) dispersion relationship generated via pulsed acoustic radiation force (ARF) excitation pulse. In this study, a multi-frequency oscillation (MFO)- excitation pulse with higher weight to higher frequencies is proposed to generate PV images via the generation of motion with energy concentrated at the target frequencies in contrast to the broadband frequency motion generated in pulsed SWE (PSWE). METHODS: The feasibility of MFO-SWE to generate PV images at 100 to 1000 Hz in steps of 100 Hz was investigated by imaging 6 and 70 kPa inclusions with 6.5 and 10.4 mm diameter and ex vivo bovine liver with and without the presence of an aberration layer and chicken muscle ex vivo, and 4T1 mouse breast tumor, in vivo with comparisons to PSWE. RESULTS: MFO-SWE-derived CNR was statistically higher than PSWE for 6 kPa (both with and without aberration) and 70 kPa (with aberration) inclusions and derived SNR of the liver was statistically higher than PSWE at higher frequency (600-1000 Hz). Quantitatively, at 600-1000 Hz, MFO-SWE improved CNR of inclusions (without and with) aberration on an average by (8.2 and 156)% and of the tumor by 122%, respectively, and improved SNR of the liver (without and with) aberration by (20.2 and 51.5)% and of chicken muscle by 72%, respectively compared to the PSWE. CONCLUSIONS AND SIGNIFICANCE: These results indicate the advantages of MFO-SWE to improve PV estimation at higher frequencies which could improve viscoelasticity quantification and feature delineation.

Optimization of the Tracking Beam Sequence in Harmonic Motion Imaging.

Harmonic motion imaging (HMI) is an ultrasound elastography technique that estimates the viscoelastic properties of tissues by inducing localized oscillatory motion using focused ultrasound (FUS). The resulting displacement, assumed to be inversely proportional to the tissue local stiffness, is estimated using an imaging array based on RF speckle tracking. In conventional HMI, this is accomplished with plane-wave (PW) imaging, which inherently suffers from low lateral resolution. Coherent PW compounding (PWC) leverages spatial and temporal resolution using synthetic focusing in transmit. In this study, we introduced focused imaging with parallel tracking in HMI and compared parallel tracking of various transmit F-numbers (F/2.6, 3, 4, and 5) qualitatively and quantitatively with PW and PWC imaging at various compounded angle ranges (6°, 12°, and 18°). An in silico model of a 56-kPa spherical inclusion (diameter: 3.6 mm) embedded in a 5.3-kPa background and a 5.3-kPa elastic phantom with cylindrical inclusions (Young's moduli: 22-56 kPa, diameters: 2.0-8.6 mm) were imaged to assess different tracking beam sequences. Speckle biasing in displacement estimation associated with parallel tracking was also investigated and concluded to be negligible in HMI. Parallel tracking in receive (Rx) resulted in 2%-7% and 8%-12% increase compared to PW imaging ( ) in HMI contrast and contrast-to-noise ratio in silico and phantoms. Focused imaging with parallel tracking in Rx was concluded to be most robust among PW and PWC imaging for displacement estimation, and its preclinical feasibility was demonstrated in postsurgical human cancerous breast tissue specimens and in vivo murine models of breast cancer.

Association of CAPN10 gene (rs3842570) polymorphism with the type 2 diabetes mellitus among the population of Noakhali region in Bangladesh: a case-control study.

Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic, and metabolically complicated disease. A large number of genes are responsible for the biogenesis of T2DM and calpain10 (CAPN10) is one of them. The association of numerous CAPN10 genetic polymorphisms in the development of T2DM has been widely studied in different populations and noticed inconclusive results. The present study is an attempt to evaluate the plausible association of CAPN10 polymorphism SNP-19 (rs3842570) with T2DM and T2DM-related anthropometric and metabolic traits in the Noakhali region of Bangladesh. This case-control study included 202 T2DM patients and 75 healthy individuals from different places in Noakhali. A significant association (p < 0.05) of SNP-19 with T2DM in co-dominant 2R/3R vs. 3R/3R (odds ratio [OR], 2.7; p=0.0014) and dominant (2R/3R) + (2R/2R) vs. 3R/3R (OR, 2.47; p=0.0011) genetic models was observed. High-risk allele 2R also showed a significant association with T2DM in the allelic model (OR, 1.67; p=0.0109). The genotypic frequency of SNP-19 variants showed consistency with Hardy-Weinberg equilibrium (p > 0.05). Additionally, SNP-19 genetic variants showed potential associations with the anthropometric and metabolic traits of T2DM patients in terms of body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. Our approach identifies the 2R/3R genotype of SNP-19 as a significant risk factor for biogenesis of T2DM in the Noakhali population. Furthermore, a large-scale study could be instrumental to correlate this finding in overall Bangladeshi population.

Breast stiffness, a risk factor for cancer and the role of radiology for diagnosis.

Over the last five decades, breast density has been associated with increased risk of developing breast cancer. Mammographically dense breasts are considered those belonging to the heterogeneously dense breasts, and extremely dense breasts subgroups according to the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). There is a statistically significant correlation between the increased mammographic density and the presence of more glandular tissue alone. However, the strength of this correlation is weak. Although the mechanisms driving breast density-related tumor initiation and progression are still unknown, there is evidence suggesting that certain molecular pathways participating in epithelial-stromal interactions may play a pivotal role in the deposition of fibrillar collagen, increased matrix stiffness, and cell migration that favor breast density and carcinogenesis. This article describes these molecular mechanisms as potential "landscapers" for breast density-related cancer. We also introduce the term "Breast Compactness" to reflect collagen density of breast tissue on chest CT scan and the use of breast stiffness measurements as imaging biomarkers for breast cancer screening and risk stratification.

Metal and metalloid bioaccumulation in dried red seaweed Hypnea musciformis and health risk assessment for consumers.

This study measured 22 metal and metalloid concentrations in Hypnea musciformis from the Bakkhali River estuary and Saint Martin's Island, Bangladesh and determined their potential impact on consumption. Student t-tests showed a significant variation in metal concentrations between the two sampling sites (p < 0.05). Mean concentrations of Co (2.49 ± 0.05 mg/kg), Fe (793.29 ± 11.76 mg/kg), Mn (368.72 ± 4.87 mg/kg), Pb (3.82 ± 0.02 mg/kg), V (11.23 ± 0.20 mg/kg) and Zn (16.60 ± 0.28 mg/kg) were higher in samples collected from the Bakkhali River estuary compared to Saint Martin's Island, while mean concentrations of Ca (484.18 ± 4.68 mg/kg), Cd (2.44 ± 0.03 mg/kg), Mg (2112.70 ± 17.80 mg/kg), Mo (1.57 ± 0.06 mg/kg), Sr (2377.57 ± 29.98 mg/kg), and Ti (258.27 ± 4.62 mg/kg) were higher in samples collected from Saint Martin's Island. Eight heavy metals (Pb, Cd, Zn, Cu, Ni, Mn, Cr, Fe) were used to assess potential health risks for adults, but no potential health risk was detected (HQ value>1). This study reveals positive Se-HBV for H. musciformis collected from both sampling sites, indicating no potential risks involved with Hg toxicity.

Machine learning algorithms distinguish discrete digital emotional fingerprints for web pages related to back pain.

Back pain is the leading cause of disability worldwide. Its emergence relates not only to the musculoskeletal degeneration biological substrate but also to psychosocial factors; emotional components play a pivotal role. In modern society, people are significantly informed by the Internet; in turn, they contribute social validation to a "successful" digital information subset in a dynamic interplay. The Affective component of medical pages has not been previously investigated, a significant gap in knowledge since they represent a critical biopsychosocial feature. We tested the hypothesis that successful pages related to spine pathology embed a consistent emotional pattern, allowing discrimination from a control group. The pool of web pages related to spine or hip/knee pathology was automatically selected by relevance and popularity and submitted to automated sentiment analysis to generate emotional patterns. Machine Learning (ML) algorithms were trained to predict page original topics from patterns with binary classification. ML showed high discrimination accuracy; disgust emerged as a discriminating emotion. The findings suggest that the digital affective "successful content" (collective consciousness) integrates patients' biopsychosocial ecosystem, with potential implications for the emergence of chronic pain, and the endorsement of health-relevant specific behaviors. Awareness of such effects raises practical and ethical issues for health information providers.

Imaging of Single Transducer-Harmonic Motion Imaging-Derived Displacements at Several Oscillation Frequencies Simultaneously.

Mapping of mechanical properties, dependent on the frequency of motion, is relevant in diagnosis, monitoring treatment response, or intra-operative surgical resection planning. While shear wave speeds at different frequencies have been described elsewhere, the effect of frequency on the "on-axis" acoustic radiation force (ARF)-induced displacement has not been previously investigated. Instead of generating single transducer-harmonic motion imaging (ST-HMI)-derived peak-to-peak displacement (P2PD) image at a particular frequency, a novel multi-frequency excitation pulse is proposed to generate P2PD images at 100-1000 Hz simultaneously. The performance of the proposed excitation pulse is compared with the ARFI by imaging 16 different inclusions (Young's moduli of 6, 9, 36, 70 kPa and diameters of 1.6, 2.5, 6.5, and 10.4 mm) embedded in an 18 kPa background. Depending on inclusion size and stiffness, the maximum CNR and contrast were achieved at different frequencies and were always higher than ARFI. The frequency, at which maximum CNR and contrast were achieved, increased with stiffness for fixed inclusion's size and decreased with size for fixed stiffness. In vivo feasibility is tested by imaging a 4T1 breast cancer mouse tumor on Day 6, 12, and 19 post-injection of tumor cells. Similar to phantoms, the CNR of ST-HMI images was higher than ARFI and increased with frequency for the tumor on Day 6. Besides, P2PD at 100-1000 Hz indicated that the tumor became stiffer with respect to the neighboring non-cancerous tissue over time. These results indicate the importance of using a multi-frequency excitation pulse to simultaneously generate displacement at multiple frequencies to better delineate inclusions or tumors.

A Comparative Review on Applications of Different Sensors for Sign Language Recognition.

Sign language recognition is challenging due to the lack of communication between normal and affected people. Many social and physiological impacts are created due to speaking or hearing disability. A lot of different dimensional techniques have been proposed previously to overcome this gap. A sensor-based smart glove for sign language recognition (SLR) proved helpful to generate data based on various hand movements related to specific signs. A detailed comparative review of all types of available techniques and sensors used for sign language recognition was presented in this article. The focus of this paper was to explore emerging trends and strategies for sign language recognition and to point out deficiencies in existing systems. This paper will act as a guide for other researchers to understand all materials and techniques like flex resistive sensor-based, vision sensor-based, or hybrid system-based technologies used for sign language until now.

Quantitative Estimation of Mechanical Anisotropy Using Acoustic Radiation Force (ARF)-Induced Peak Displacements (PD): In Silico and Experimental Demonstration.

Elastic degree of anisotropy (DoA) is a diagnostically relevant biomarker in muscle, kidney, breast, and other organs. Previously, elastic DoA was qualitatively assessed as the ratio of peak displacements (PD) achieved with the long-axis of a spatially asymmetric Acoustic Radiation Force Impulse (ARFI) excitation point spread function (PSF) aligned along versus across the axis of symmetry (AoS) in transversely isotropic materials. However, to better enable longitudinal and cross-sectional analyses, a quantitative measure of elastic DoA is desirable. In this study, qualitative ARFI PD ratios are converted to quantitative DoA, measured as the ratio of longitudinal over transverse shear elastic moduli, using a model empirically derived from Field II and finite element method (FEM) simulations. In silico, the median absolute percent error (MAPE) in ARFI-derived shear moduli ratio (SMR) was 1.75%, and predicted SMRs were robust to variations in transverse shear modulus, Young's moduli ratio, speed of sound, attenuation, density, and ARFI excitation PSF dimension. Further, ARFI-derived SMRs distinguished two materials when the true SMRs of the compared materials differed by as little as 10%. Experimentally, ARFI-derived SMRs linearly correlated with the corresponding ratios measured by Shear Wave Elasticity Imaging (SWEI) in excised pig skeletal muscle ( [Formula: see text], MAPE = 13%) and in pig kidney, in vivo ( [Formula: see text], MAPE = 5.3%). These results demonstrate the feasibility of using the ARFI PD to quantify elastic DoA in biological tissues.

Adiponectin gene polymorphisms associated with diabetes mellitus: A descriptive review.

Diabetes is currently a growing concern of the age. Prevention and treatment of diabetes is a global health priority. Adiponectin is an adipocyte derived protein hormone that enhances insulin sensitivity and ameliorates diabetes by enhancing fatty acid oxidation and glucose uptake in skeletal muscle and reducing glucose production in the liver. Low serum adiponectin concentrations are associated with diabetes, central obesity, insulin resistance and metabolic syndrome. Adiponectin gene is located on chromosome 3q27, where a locus of susceptibility to diabetes was mapped. Several cross-sectional studies showed that single nucleotide polymorphisms (SNPs) in adiponectin gene (ADIPOQ) were associated with diabetes. SNPs in ADIPOQ help in assessing the association of common variants with levels of adiponectin and the risk of diabetes. Two common SNPs, rs2241766 and rs1501299, have been linked significantly to type 1 diabetes mellitus which endow the world with a block of haplotypes. Experimental evidences also suggest that rs1501299, rs2241766, rs266729, rs17366743, rs17300539, rs182052, rs822396, rs17846866, rs3774261 and rs822393 are significantly associated with type 2 diabetes mellitus which is the predominant form of the disease. In addition, rs2241766 and rs266729 are extensively associated with gestational diabetes, a condition that develops in women during pregnancy. Therefore not a particular single mutation but a number of SNPs in adiponectin gene could be a risk factor for developing diabetes among the individuals worldwide. This study firmly suggests that adiponectin plays a crucial role in the pathogenesis of type 1, type 2 and gestational diabetes mellitus.

Feasibility of Harmonic Motion Imaging Using a Single Transducer: In Vivo Imaging of Breast Cancer in a Mouse Model and Human Subjects.

Harmonic motion imaging (HMI) interrogates the mechanical properties of tissues by simultaneously generating and tracking harmonic oscillation using focused ultrasound and imaging transducers, respectively. Instead of using two transducers, the objective of this work is to develop a single transducer HMI (ST-HMI) to both generate and track harmonic motion at "on-axis" to the force for facilitating data acquisition. In ST-HMI, the amplitude-modulated force was generated by modulating excitation pulse duration and tracking of motion was performed by transmitting tracking pulses interleaved between excitation pulses. The feasibility of ST-HMI was performed by imaging two elastic phantoms with three inclusions (N = 6) and comparing it with acoustic radiation force impulse (ARFI) imaging, in vivo longitudinal monitoring of 4T1, orthotropic breast cancer mice (N = 4), and patients (N = 3) with breast masses in vivo. Six inclusions with Young's moduli of 8, 10, 15, 20, 40, and 60 kPa were embedded in a 5 kPa background. The ST-HMI-derived peak-to-peak displacement (P2PD) successfully detected all inclusions with [Formula: see text] of the linear regression between the P2PD ratio of background to inclusion versus Young's moduli ratio of inclusion to background. The contrasts of 10 and 15 kPa inclusions were higher in ST-HMI than ARFI-derived images. In the mouse study, the median P2PD ratio of tumor to non-cancerous tissues was 3.0, 5.1, 6.1, and 7.7 at 1, 2, 3, and 4 weeks post-injection of the tumor cells, respectively. In the clinical study, ST-HMI detected breast masses including fibroadenoma, pseudo angiomatous stromal hyperplasia, and invasive ductal carcinoma with a P2PD ratio of 1.37, 1.61, and 1.78, respectively. These results indicate that ST-HMI can assess the mechanical properties of tissues via generation and tracking of harmonic motion "on-axis" to the ARF. This study is the first step towards translating ST-HMI in clinics.

A 1.5-D Array for Acoustic Radiation Force (ARF)-Induced Peak Displacement-Based Tissue Anisotropy Assessment With a Row-Column Excitation Method.

Many biological tissues, including muscle or kidney, are mechanically anisotropic, and the degree of anisotropy (DoA) in mechanical properties is diagnostically relevant. DoA can be assessed either using the ratio of shear wave velocities (SWVs) or acoustic radio forced impulse (ARFI)-induced peak displacements (PD) measured longitudinal over transverse orientations. Whether using SWV or PD as a basis, DoA expressed as the ratio of values requires 90° transducer rotation when a linear array is employed. This large rotation angle is prone to misalignment errors. One solution is the use of a fully sampled matrix array for electronic rotation of point spread function (PSF). However, the challenges of matrix array are its high fabrication cost and complicated fabrication procedures. The cheaper and simpler alternative of matrix array is the use of a row-column array. A 3×64 elements 1.5-D array with a row-column excitation mode is proposed to assess DoA in mechanical properties using the PD ratio. Different numbers of elements in elevational and lateral directions were selected to have orthogonal ARFI excitation beams without rotating the transducer. A custom-designed flex circuit was used to fabricate the array with a simpler electrode connection than a fully sampled matrix array. The performance of the array was evaluated in Field II simulation and experiment. The output pressure was 0.57-MPa output under a 40- [Formula: see text] excitation with a -6-dB point spread dimension of 14×4 mm2 in orthogonal directions. The PD was measured to be [Formula: see text] in an isotropic elastic phantom with Young's modulus of 5.4 kPa. These results suggest that the array is capable of assessing DoA using PD ratio without physical rotation of the transducer. The array has the potential to reduce the misalignment errors for DoA assessment.

Electronic Point Spread Function Rotation Using a Three-Row Transducer for ARFI-Based Elastic Anisotropy Assessment: In Silico and Experimental Demonstration.

Degree of anisotropy (DoA) of mechanical properties has been assessed as the ratio of acoustic radiation force impulse (ARFI)-induced peak displacements (PDs) achieved using spatially asymmetric point spread functions (PSFs) that are rotated 90° to each other. Such PSF rotation has been achieved by manually rotating a linear array transducer, but manual rotation is cumbersome and prone to misalignment errors and higher variability in measurements. The purpose of this work is to evaluate the feasibility of electronic PSF rotation using a three-row transducer, which will reduce variability in DoA assessment. A Siemens 9L4, with 3×192 elements, was simulated in Field II to generate spatially asymmetric ARFI PSFs that were electronically rotated 63° from each other. Then, using the finite element method (FEM), PD due to the ARFI excitation PSFs in 42 elastic, incompressible, transversely isotropic (TI) materials with shear moduli ratios of 1.0-6.0 were modeled. Finally, the ratio of PDs achieved using the two rotated PSFs was evaluated to assess elastic DoA. DoA increased with increasing shear moduli ratios and distinguished materials with 17% or greater difference in shear moduli ratios (Wilcoxon, ). Experimentally, the ratio of PDs achieved using ARFI PSF rotated 63° from each other distinguished the biceps femoris muscle from two pigs, which had median shear moduli ratios of 4.25 and 3.15 as assessed by shear wave elasticity imaging (SWEI). These results suggest that ARFI-based DoA assessment can be achieved without manual transducer rotation using a three-row transducer capable of electronically rotating PSFs by 63°. It is expected that electronic PSF rotation will facilitate data acquisitions and improve the reproducibility of elastic anisotropy assessments.

Viscoelastic Response Ultrasound Derived Relative Elasticity and Relative Viscosity Reflect True Elasticity and Viscosity: In Silico and Experimental Demonstration.

Viscoelastic response (VisR) ultrasound characterizes the viscoelastic properties of tissue by fitting acoustic radiation force (ARF)-induced displacements in the region of ARF excitation to a 1-D mass-spring-damper (MSD) model. Elasticity and viscosity are calculated separately but relative to the applied ARF amplitude. We refer to these parameters as "relative elasticity (RE)" and "relative viscosity (RV)." We herein test the hypothesis that RE and RV linearly correlate to true elasticity and viscosity in tissue. VisR imaging was simulated in 144 homogeneous viscoelastic materials with varying elasticities and viscosities. Derived RE linearly correlated with material elasticity and varied by an average of 2.52% when the material viscosity changed from 0.1 to 1.3 Pa · s. Derived RV linearly correlated with material viscosity but varied by an average of 102.5% when material elasticity changed from 3.33 to 20 kPa. The effect of elasticity on RV measurement was compensated using the slope of the linear relationship between RV and natural frequency ( ωtextn ). After compensation, RV [Formula: see text] (elasticity compensated RV) linearly correlated with material viscosity and varied by less than 1.00% on average when the modeled shear elastic modulus changed from 3.3 to 20 kPa. In addition to elasticity compensation, variation in ARF amplitude over depth was compensated, yielding REDC and [Formula: see text]. REDC and [Formula: see text] successfully contrasted elastic and viscous inclusions, respectively, in three simulated phantoms. Experimentally, in the homogeneous oil-in-gelatin phantoms and excised livers, REDC linearly correlated with shear wave dispersion ultrasound vibrometry (SDUV) derived shear elastic modulus, and [Formula: see text] linearly correlated with SDUV-derived shear viscosity. In excised livers containing viscoelastic oil-in-gelatin inclusions, the inclusions were successfully contrasted from the liver background by both REDC and [Formula: see text]. These results suggest that RE and RV are relevant for qualitatively assessing the elastic and viscous properties of tissue.