Study on localized thermal expansion gradient formation for acoustic wave generation in a novel thermoacoustic imaging modality

Thermoacoustics is the process of generation of sound by heat or vice versa. Volume generated thermoacoustic signals can be produced by thermal expansion induced volume contraction and rarefaction inside a target body. Thermoacoustic imaging uses this modality to obtain vivid insight into the internal structure of target body, both for non-destructive testing and biomedical imaging. Any penetrating pulsed radiation can be used for such purpose, including microwave where the modality is called thermoacoustics in general or by incident light waves where the same is termed as photoacoustics. The current thesis establishes the theoretical basis for a novel thermoacoustic imaging modality where pulsed ultrasound is used as the incident penetraing source. A formal forward transient theoretical eqution set is derived based on established transient acoustic propagation models and the problem is solved using a commercially available FEM software. The results are then compared with experimental results and considerable agreement has been observed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Optimization of operating frequency of acoustic transducers for obtaining maximum temperature in HIFU based therapeutic ablation

High intensity Focus Ultrasound therapy relies on acoustic power absorbed by tissue. Acoustic absorption is a function of frequency: while a relatively lower frequency allows the beam to propagate farther in the tissue, the absorption, and, hence, the heat generated at the focal point is poor. At higher frequencies, on the other hand, tissue at the focal point is capable of absorbing most of the incoming acoustic energy, but loss along the propagation path significantly reduces the strength of the received signal. One figure of merit for finding the optimal frequency is the spatial peak of the acoustic power absorption density. In this paper, we analyze the same problem with the figure of merit taken as the peak temperature at the focal point and show that this may lead to a different frequency at which this value is maximized

Integrated HIFU Drive System on a Chip for CMUT-Based Catheter Ablation System

63rd IEEE International Solid-State Circuits Conference (ISSCC) (2016 : San Francisco, CA)Conventional High Intensity Focused Ultrasound (HIFU) is a therapeutic modality which is extracorporeally administered. In applications where a relatively small HIFU lesion is required, an intravascular HIFU probe can be deployed to the ablation site. In this paper, we demonstrate the design and implementation a fully integrated HIFU drive system on a chip to be placed on a 6 Fr catheter probe. An 8-element capacitive micromachined ultrasound transducer (CMUT) ring array of 2 mm diameter has been used as the ultrasound source. The driver chip is fabricated in 0.35 mu m AMS high-voltage CMOS technology and comprises eight continuous-wave (CW) high-voltage CMUT drivers (10.9 ns and 9.4 ns rise and fall times at 20 V-pp output into a 15 pF), an eight-channel digital beamformer (8-12 MHz output frequency with 11.25 degrees phase accuracy) and a phase locked loop with an integrated VCO as a tunable clock source (128-192 MHz). The chip occupies 1.85 x 1.8 mm(2) area including input and output (I/O) pads. When the transducer array is immersed in sunflower oil and driven by the IC with eight 20 Vpp CW pulses at 10 MHz, real-time thermal images of the HIFU beam indicate that the focal temperature rises by 16.8 degrees C in 11 seconds. Each HV driver consumes around 67 mW of power when driving the CMUT array at 10 MHz, which adds up to 560 m W for the whole chip. FEM based analysis reveals that the outer surface temperature of the catheter is expected to remain below the 42 degrees C tissue damage limit during therapy

Fabrication of High-Efficiency CMUTs With Reduced Parasitics Using Embedded Metallic Layers

The transmit and receive sensitivity of the capacitive micromachined ultrasonic transducer (CMUT) is proportional to the active device capacitance formed by the vacuum gap of the device, and an insulation layer between the gap and the device electrode. In the sacrificial release process of CMUT fabrication, this insulation layer cannot be made arbitrarily thin due to conformality issues. In this paper, we propose and prove the applicability of a micromachining technique by which metallic sacrificial islands are embedded inside grooves etched on the substrate, yielding topology free surfaces. This obviates the conformality requirement, and enables the growth of a thinner insulation layer which reduces the effective gap height, and, hence, improves sensitivity. Embedded metalic layers, which provide a flat surface for subsequent process steps, have also been used as the back electrode of the CMUT, which facilitated the manufacturing of devices with reduced stray capacitance on thermally oxidized wafers. CMUT devices were fabricated using the proposed technique, and their parameters were measured to justify the performance improvement. While the dc bias requirement is reduced by 19%, the output sensitivity of the device is 10% higher than that of the conventional CMUT, and spurious capacitance is decreased by 70%.This work was supported by The Scientific and Technological Research Council of Turkey under Grant 112E048. This work was presented at the IEEE Sensors Conference 2015. The associate editor coordinating the review of this paper and approving it for publication was Dr. Rosario Morello

Design of a Driver IC for an Ultrasound Catheter Ablation System

IEEE International Ultrasonics Symposium (IUS) (2014 : Chicago, IL)High Intensity Focused Ultrasound (HIFU) is generally administered externally, or through body orifices such as the esophagus, the urethra, the uterus, or the rectum. The devices used in conventional treatment are not suitable to be used in endoscopic interventions or in intravascular catheterization due to their dimensions. This paper presents the design of a drive integrated circuit for driving a CMUT therapy array of 2 mm diameter such that whole device fit through key holes in endoscopic treatment or through vessels. The proposed ASIC is composed of (1) an 8 channel drive signal generator, (2) 8 high voltage drivers, and (3) a PLL for the local generation of a high frequency tunable master clock signal based on a low frequency reference. All designs are in austriamicrosystems h35 High-Voltage CMOS technology with 1.3x3 mm(2) die area including ESD protection pads

A High Frequency CMUT Ring Array for Small Spot Size HIFU

IEEE International Ultrasonics Symposium (IUS) (2016 : Tours, FRANCE)The spot size of HIFU lesion depends on many parameters like size of the transducer, frequency of operation, sonication time etc. A recently developed CMUT based HIFU application for corneal keratoplasty require high localized temperature rise within a very small confined area as short as 300-500 mu m in length. To simplify the electrical connection requirements for this relatively small sized array, even and odd numbered array elements are electrically bundled and connected to two pads through which the drive signal is applied. As the array is CMUT based, the same RF signal is applied to both element groups with DC bias voltages of opposite polarity resulting in a 180. phase difference to provide Fresnel focusing capability. This also negates the necessity of a high-frequency phased array driver, and replaces it with a single RF signal source. COMSOL simulation of ring arrays in water has been used to verify the FWHM spot length for a Fresnel focusing CMUT based HIFU device, to infer that alternated phase excitation can be used. Fresnel arrays of 1mm diameter are designed, fabricated and tested for such HIFU applications

Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundAccurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. MethodsTo estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. FindingsDuring the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. InterpretationFertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. FundingBill & Melinda Gates Foundation