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Historic timber structures feature timber joinery connections that use interlocking geometries rather than fasteners. While timber construction since has gradually favored metallic fasteners, the longevity of historic timber structures utilizing joinery connections demonstrates their feasibility in structural systems and potential to enable sustainable constructions. Advancements in digital fabrication imply the ability to revitalize these complex geometries in competition with conventional fasteners. However, characterization of the mechanical behavior of joinery connections remains to be calibrated across analytical, experimental, and numerical models, let alone systematized across different geometric variations. This research examines the calibration between analytical models and experimental tests for the Nuki joint, a simple beam-through-mortised-column joinery connection. This paper shows that general elastoplastic behavior matches between models, and the analytical model can be calibrated to predict initial stiffnesses within 20% of those determined experimentally. Mismatches between models reveal challenges in calibrating across models: material irregularity of wood and fabrication tolerances.

Under certain circumstances, such as during the current COVID-19 outbreak, pregnant women can be a target for respiratory infection, and lung examination may be required as part of their clinical evaluation, ideally while avoiding exposure to radiation. We propose a practical approach for obstetricians/gynecologists to perform lung ultrasound examination, discussing potential applications, semiology and practical aspects, which could be of particular importance in emergency situations, such as the current pandemic infection of COVID-19. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Lung ultrasound examination has been demonstrated to be an accurate imaging method to detect pulmonary and pleural conditions. During pregnancy, there is a need for rapid assessment of the maternal lung in patients with suspected coronavirus disease 2019. We report our experience on lung ultrasound examination in the diagnosis of coronavirus disease 2019 pneumonia in a pregnant woman. Typical ultrasound features of this pulmonary pathology, including diffuse hyperechoic vertical artifacts with thickened pleural line and “white lung” with patchy distribution, were observed. We suggest point-of-care lung ultrasound examination as a diagnostic imaging tool in pregnant women with suspected coronavirus disease 2019.

Lung ultrasound examination has been demonstrated to be an accurate imaging method to detect pulmonary and pleural conditions. During pregnancy, there is a need for rapid assessment of the maternal lung in patients with suspected coronavirus disease 2019. We report our experience on lung ultrasound examination in the diagnosis of coronavirus disease 2019 pneumonia in a pregnant woman. Typical ultrasound features of this pulmonary pathology, including diffuse hyperechoic vertical artifacts with thickened pleural line and “white lung” with patchy distribution, were observed. We suggest point-of-care lung ultrasound examination as a diagnostic imaging tool in pregnant women with suspected coronavirus disease 2019.

Under certain circumstances, such as during the current COVID-19 outbreak, pregnant women can be a target for respiratory infection, and lung examination may be required as part of their clinical evaluation, ideally while avoiding exposure to radiation. We propose a practical approach for obstetricians/gynecologists to perform lung ultrasound examination, discussing potential applications, semiology and practical aspects, which could be of particular importance in emergency situations, such as the current pandemic infection of COVID-19. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

A novel type of application for the exploration of enclosed or otherwise difficult to access environments requires large quantities of miniaturized sensor nodes to perform measurements while they traverse the environment in a “go with the flow” approach. Examples of these are the exploration of underground cavities and the inspection of industrial pipelines or mixing tanks, all of which have in common that the environments are difficult to access and do not allow position determination using e.g. GPS or similar techniques. The sensor nodes need to be scaled down towards the millimetre range in order to physically fit through the narrowest of parts in the environments and should measure distances between each other in order to enable the reconstruction of their positions relative to each other in offline analysis. Reaching those levels of miniaturization and enabling reconstruction functionality requires: 1) novel reconstruction algorithms that can deal with the specific measurement limitations and imperfections of millimetre-sized nodes, and 2) improved understanding of the relation between the highly constraint hardware design space of the sensor nodes and the reconstruction algorithms. To this end, this work provides a novel and highly robust sensor swarm reconstruction algorithm and studies the effect of hardware design trade-offs on its performance. Our findings based on extensive simulations, which push the reconstruction algorithm to its breaking point, provide important guidelines for the future development of millimetre-sized sensor nodes.

A novel type of application for the exploration of enclosed or otherwise difficult to access environments requires large quantities of miniaturized sensor nodes to perform measurements while they traverse the environment in a “go with the flow” approach. Examples of these are the exploration of underground cavities and the inspection of industrial pipelines or mixing tanks, all of which have in common that the environments are difficult to access and do not allow position determination using e.g. GPS or similar techniques. The sensor nodes need to be scaled down towards the millimetre range in order to physically fit through the narrowest of parts in the environments and should measure distances between each other in order to enable the reconstruction of their positions relative to each other in offline analysis. Reaching those levels of miniaturization and enabling reconstruction functionality requires: 1) novel reconstruction algorithms that can deal with the specific measurement limitations and imperfections of millimetre-sized nodes, and 2) improved understanding of the relation between the highly constraint hardware design space of the sensor nodes and the reconstruction algorithms. To this end, this work provides a novel and highly robust sensor swarm reconstruction algorithm and studies the effect of hardware design trade-offs on its performance. Our findings based on extensive simulations, which push the reconstruction algorithm to its breaking point, provide important guidelines for the future development of millimetre-sized sensor nodes.

To investigate quantitative 3-D dynamic contrast-enhanced ultrasound (DCE-US) and, in particular 3-D contrast-ultrasound dispersion imaging (CUDI), for prostate cancer detection and localization, 43 patients referred for 10-12-core systematic biopsy underwent 3-D DCE-US. For each 3-D DCE-US recording, parametric maps of CUDI-based and perfusion-based parameters were computed. The parametric maps were divided in regions, each corresponding to a biopsy core. The obtained parameters were validated per biopsy location and after combining two or more adjacent regions. For CUDI by correlation (r) and for the wash-in time (WIT), a significant difference in parameter values between benign and malignant biopsy cores was found (p < 0.001). In a per-prostate analysis, sensitivity and specificity were 94% and 50% for r, and 53% and 81% for WIT. Based on these results, it can be concluded that quantitative 3-D DCE-US could aid in localizing prostate cancer. Therefore, we recommend follow-up studies to investigate its value for targeting biopsies.

A novel type of application for the exploration of enclosed or otherwise difficult to access environments requires large quantities of miniaturized sensor nodes to perform measurements while they traverse the environment in a “go with the flow” approach. Examples of these are the exploration of underground cavities and the inspection of industrial pipelines or mixing tanks, all of which have in common that the environments are difficult to access and do not allow position determination using e.g. GPS or similar techniques. The sensor nodes need to be scaled down towards the millimetre range in order to physically fit through the narrowest of parts in the environments and should measure distances between each other in order to enable the reconstruction of their positions relative to each other in offline analysis. Reaching those levels of miniaturization and enabling reconstruction functionality requires: 1) novel reconstruction algorithms that can deal with the specific measurement limitations and imperfections of millimetre-sized nodes, and 2) improved understanding of the relation between the highly constraint hardware design space of the sensor nodes and the reconstruction algorithms. To this end, this work provides a novel and highly robust sensor swarm reconstruction algorithm and studies the effect of hardware design trade-offs on its performance. Our findings based on extensive simulations, which push the reconstruction algorithm to its breaking point, provide important guidelines for the future development of millimetre-sized sensor nodes.

To investigate quantitative 3-D dynamic contrast-enhanced ultrasound (DCE-US) and, in particular 3-D contrast-ultrasound dispersion imaging (CUDI), for prostate cancer detection and localization, 43 patients referred for 10-12-core systematic biopsy underwent 3-D DCE-US. For each 3-D DCE-US recording, parametric maps of CUDI-based and perfusion-based parameters were computed. The parametric maps were divided in regions, each corresponding to a biopsy core. The obtained parameters were validated per biopsy location and after combining two or more adjacent regions. For CUDI by correlation (r) and for the wash-in time (WIT), a significant difference in parameter values between benign and malignant biopsy cores was found (p < 0.001). In a per-prostate analysis, sensitivity and specificity were 94% and 50% for r, and 53% and 81% for WIT. Based on these results, it can be concluded that quantitative 3-D DCE-US could aid in localizing prostate cancer. Therefore, we recommend follow-up studies to investigate its value for targeting biopsies.

Objectives: The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. Materials and Methods: Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. Results: The combination of the spatiotemporal correlation (r), mean transit time (μ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), μ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. Conclusions: Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. Key points: • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

To validate new imaging modalities for prostate cancer, images must be three-dimensionally correlated with the histological ground truth. In this work, an interpolation algorithm is described to construct a reliable three-dimensional reference from two-dimensional (2D) histological slices. Eight clinically relevant in silico phantoms were designed to represent difficult-to-reconstruct tumour structures. These phantoms were subjected to different slicing procedures. Additionally, controlled errors were added to investigate the impact of varying slicing distance, front-face orientation, and inter-slice misalignment on the reconstruction performance. Using a radial-basis-function interpolation algorithm, the 2D data were reconstructed in three dimensions. Our results demonstrate that slice thicknesses up to 4 mm can be used to reliably reconstruct tumours of clinically significant size; the surfaces lay within a 1.5 mm 90%-error margin from each other and the volume difference between the original and reconstructed tumour structures does not exceed 10%. With these settings, Dice coefficients above 0.85 are obtained. The presented interpolation algorithm is able to reconstruct clinically significant tumour structures from 2D histology slices. Errors occurring are in the order of magnitude of common registration artefacts. The method’s applicability to real histopathological data is also shown in two resected prostates. An inter-slice spacing of 4 mm or less is recommended during histopathology; the use of a 1.5 mm error margin along the tumour contours can then ensure reliable mapping of the ground truth.

Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype.With the aim of localizing angiogenic activity in a noninvasive manner, Dynamic Contrast Enhanced Ultrasound (DCEUS) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsyproven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiveroperating- characteristic curve area of 0.85) for the detection of prostate cancer.

To validate new imaging modalities for prostate cancer, images must be three-dimensionally correlated with the histological ground truth. In this work, an interpolation algorithm is described to construct a reliable three-dimensional reference from two-dimensional (2D) histological slices. Eight clinically relevant in silico phantoms were designed to represent difficult-to-reconstruct tumour structures. These phantoms were subjected to different slicing procedures. Additionally, controlled errors were added to investigate the impact of varying slicing distance, front-face orientation, and inter-slice misalignment on the reconstruction performance. Using a radial-basis-function interpolation algorithm, the 2D data were reconstructed in three dimensions. Our results demonstrate that slice thicknesses up to 4 mm can be used to reliably reconstruct tumours of clinically significant size; the surfaces lay within a 1.5 mm 90%-error margin from each other and the volume difference between the original and reconstructed tumour structures does not exceed 10%. With these settings, Dice coefficients above 0.85 are obtained. The presented interpolation algorithm is able to reconstruct clinically significant tumour structures from 2D histology slices. Errors occurring are in the order of magnitude of common registration artefacts. The method’s applicability to real histopathological data is also shown in two resected prostates. An inter-slice spacing of 4 mm or less is recommended during histopathology; the use of a 1.5 mm error margin along the tumour contours can then ensure reliable mapping of the ground truth.

Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype.With the aim of localizing angiogenic activity in a noninvasive manner, Dynamic Contrast Enhanced Ultrasound (DCEUS) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsyproven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiveroperating- characteristic curve area of 0.85) for the detection of prostate cancer.

OBJECTIVE: The role of angiogenesis in cancer growth has stimulated research aimed at non-invasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasoundcontrast- agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa.METHODS: First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology.RESULTS: A monotonic relationship between dispersion and mutual information was demonstrated. The in-vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p=0.21-0.24) to that obtained by linear similarity measures (0.74-0.75) and (p<0.05) to that by conventional perfusion parameters (0.70).CONCLUSION: Mutual information between neighboring TICs can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization.SIGNIFICANCE: An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.

Higher microvascular density with tortuous and irregular vessels are hallmarks of cancer vasculature. These alterations can be captured by contrast ultrasound dispersion imaging (CUDI) and acoustic angiography (AA) at different scales: CUDI aims at obtaining an implicit measure of structural alteration by determining the dispersion kinetics of contrast agents. At a smaller scale, AA images the vascular architecture by detecting the high-frequency components generated with ultrasound contrast agents (UCA). This work shows the performance of these techniques by imaging cancerous and control regions in 3 rat xenograft models. Furthermore, it investigates the diagnostic value of the vascular features extracted using CUDI and AA with the aim to answer the question: does CUDI reveal changes in vascular tortuosity?

Fetal heart rate (fHR) monitoring is usually performed by Doppler ultrasound (US) techniques. For reliable fHR measurements it is required that the fetal heart is located within the US beam. In clinical practice, clinicians palpate the maternal abdomen to identify the fetal presentation and then the US transducer is fixated on the maternal abdomen where the best fHR signal can be obtained. Finding the optimal transducer position is done by listening to the strength of the Doppler audio output and relying on a signal quality indicator of the cardiotocographic (CTG) measurement system. Due to displacement of the US transducer or displacement of the fetal heart out of the US beam, the fHR signal may be lost. Therefore, it is often necessary that the obstetrician repeats the tedious procedure of US transducer positioning to avoid long periods of fHR signal loss. An intuitive US transducer positioning aid would be highly desirable to increase the work flow for the clinical staff. In this paper, the possibility to determine the fetal heart location with respect to the transducer by exploiting the received signal power in the transducer elements is shown. A commercially available US transducer used for fHR monitoring is connected to an US open platform, which allows individual driving of the elements and raw US data acquisition. Based on the power of the received Doppler signals in the transducer elements, the fetal heart location can be estimated. A beating fetal heart setup was designed and realized for validation. The experimental results show the feasibility of estimating the fetal heart location with the proposed method. This can be used to support clinicians in finding the optimal transducer position for fHR monitoring more easily.

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

Moser Park is a property in Allen County, Indiana, managed by New Haven Parks and Recreation. We conducted a plant survey within the forested section of the park, identifying and quantifying abundance of understory, midstory, and overstory plants. We calculated species richness and Shannon's index for all three strata and tested for relationships with environmental variables (i.e., canopy cover, soil compaction, litter depth, and light availability). The majority of understory species are typically associated with disturbed habitats, with very little resemblance to natural, pre-settlement habitat (i.e., low coefficient of conservation values). Understory cover was dominated by Rubus allegheniensis. Midstory stratum was less diverse than the understory and was dominated by an abundance of Fraxinus pennsylvanica, which was also an important species in the overstory. The forest at Moser Park matched the Hackberry-American Elm-Green Ash forest type. There was a lack of both Quercus and many Acer species within Moser Park that are common in the region. Because of the distinct soil types, and disturbance history, a relatively uncommon forest type for the region has developed in Moser Park that differs from the majority of forested land surrounding it.

Higher microvascular density with tortuous and irregular vessels are hallmarks of cancer vasculature. These alterations can be captured by contrast ultrasound dispersion imaging (CUDI) and acoustic angiography (AA) at different scales: CUDI aims at obtaining an implicit measure of structural alteration by determining the dispersion kinetics of contrast agents. At a smaller scale, AA images the vascular architecture by detecting the high-frequency components generated with ultrasound contrast agents (UCA). This work shows the performance of these techniques by imaging cancerous and control regions in 3 rat xenograft models. Furthermore, it investigates the diagnostic value of the vascular features extracted using CUDI and AA with the aim to answer the question: does CUDI reveal changes in vascular tortuosity?

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

OBJECTIVE: The role of angiogenesis in cancer growth has stimulated research aimed at non-invasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasoundcontrast- agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa.METHODS: First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology.RESULTS: A monotonic relationship between dispersion and mutual information was demonstrated. The in-vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p=0.21-0.24) to that obtained by linear similarity measures (0.74-0.75) and (p<0.05) to that by conventional perfusion parameters (0.70).CONCLUSION: Mutual information between neighboring TICs can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization.SIGNIFICANCE: An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.

Fetal heart rate (fHR) monitoring is usually performed by Doppler ultrasound (US) techniques. For reliable fHR measurements it is required that the fetal heart is located within the US beam. In clinical practice, clinicians palpate the maternal abdomen to identify the fetal presentation and then the US transducer is fixated on the maternal abdomen where the best fHR signal can be obtained. Finding the optimal transducer position is done by listening to the strength of the Doppler audio output and relying on a signal quality indicator of the cardiotocographic (CTG) measurement system. Due to displacement of the US transducer or displacement of the fetal heart out of the US beam, the fHR signal may be lost. Therefore, it is often necessary that the obstetrician repeats the tedious procedure of US transducer positioning to avoid long periods of fHR signal loss. An intuitive US transducer positioning aid would be highly desirable to increase the work flow for the clinical staff. In this paper, the possibility to determine the fetal heart location with respect to the transducer by exploiting the received signal power in the transducer elements is shown. A commercially available US transducer used for fHR monitoring is connected to an US open platform, which allows individual driving of the elements and raw US data acquisition. Based on the power of the received Doppler signals in the transducer elements, the fetal heart location can be estimated. A beating fetal heart setup was designed and realized for validation. The experimental results show the feasibility of estimating the fetal heart location with the proposed method. This can be used to support clinicians in finding the optimal transducer position for fHR monitoring more easily.

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time–intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r2 = 0.91 (r2 > 0.75 for 78.6% of all prostate pixels) compared with r2 = 0.91 (r2 > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Key Words Prostate cancer; Contrast-enhanced ultrasound; Ultrasound contrast agents; Dilution curve; Transabdominal ultrasound; Transrectal ultrasound; Perfusion

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time–intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r2 = 0.91 (r2 > 0.75 for 78.6% of all prostate pixels) compared with r2 = 0.91 (r2 > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Key Words Prostate cancer; Contrast-enhanced ultrasound; Ultrasound contrast agents; Dilution curve; Transabdominal ultrasound; Transrectal ultrasound; Perfusion

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

A method is presented in which a (large) swarm of sensor motes perform simple ultrasonic ranging measurements. The method allows to localize the motes within the swarm, and at the same time, map the environment which the swarm has traversed. The motes float passively uncontrolled through the environment and do not need any other sensor information or external reference other than a start and end point. Once the motes are retrieved, the stored data can be converted into the motes relative positions and a map describing the geometry of the environment. This method provides the possibility to map inaccessible or unknown environments where electro-magnetic signals, such as GPS or radio, cannot be used and where placing beacon points is very hard. An example is underground piping systems transporting liquids. Size and energy constraints together with the occurrence of reverberations pose challenges in the way the motes perform their measurements and collect their data. A minimalistic approach in the use of ultrasound is pursued, using an orthogonal frequency division multiplexing technique for the identification of motes. Simulations and scaled air-coupled 45–65 kHz experimental measurements have been performed and show feasibility of the concept.

Background Nowadays, ultrasound techniques have not gained importance in the diagnosis and monitoring of lung pathologies yet because of the high mismatch in acoustic impedance between air and intercostal tissues. However, it is evident that B-mode imaging provides important information on pulmonary tissue, although in the form of image artifacts. Findings Notwithstanding medical evidences, there exists no ultrasound-based method dedicated to the lung, hampering de facto the full exploitation of ultrasound potentials. A chance is given by the experience acquired in other fields, where acoustic attenuation is used to estimate concentrations of suspended particles in liquids and of air-bubbles in aerated foods. Conclusions Custom hardware must be developed since commercial echographic equipment has been optimized to work with low acoustic impedance mismatches, and, in general, does not provide the primitive radiofrequency (RF) signals nor the possibility to tune key acquisition parameters such as ultrasound carrier frequency and pulse bandwidth, which are surely needed for our application.

Background Nowadays, ultrasound techniques have not gained importance in the diagnosis and monitoring of lung pathologies yet because of the high mismatch in acoustic impedance between air and intercostal tissues. However, it is evident that B-mode imaging provides important information on pulmonary tissue, although in the form of image artifacts. Findings Notwithstanding medical evidences, there exists no ultrasound-based method dedicated to the lung, hampering de facto the full exploitation of ultrasound potentials. A chance is given by the experience acquired in other fields, where acoustic attenuation is used to estimate concentrations of suspended particles in liquids and of air-bubbles in aerated foods. Conclusions Custom hardware must be developed since commercial echographic equipment has been optimized to work with low acoustic impedance mismatches, and, in general, does not provide the primitive radiofrequency (RF) signals nor the possibility to tune key acquisition parameters such as ultrasound carrier frequency and pulse bandwidth, which are surely needed for our application.

A method is presented in which a (large) swarm of sensor motes perform simple ultrasonic ranging measurements. The method allows to localize the motes within the swarm, and at the same time, map the environment which the swarm has traversed. The motes float passively uncontrolled through the environment and do not need any other sensor information or external reference other than a start and end point. Once the motes are retrieved, the stored data can be converted into the motes relative positions and a map describing the geometry of the environment. This method provides the possibility to map inaccessible or unknown environments where electro-magnetic signals, such as GPS or radio, cannot be used and where placing beacon points is very hard. An example is underground piping systems transporting liquids. Size and energy constraints together with the occurrence of reverberations pose challenges in the way the motes perform their measurements and collect their data. A minimalistic approach in the use of ultrasound is pursued, using an orthogonal frequency division multiplexing technique for the identification of motes. Simulations and scaled air-coupled 45–65 kHz experimental measurements have been performed and show feasibility of the concept.

The speed of sound in the human body limits the achievable data acquisition rate of pulsed ultrasound scanners. To overcome this limitation, parallel beamforming techniques are used in ultrasound 2-D and 3-D imaging systems. Different parallel beamforming approaches have been proposed. They may be grouped into two major categories: parallel beamforming in reception and parallel beamforming in transmission. The first category is not optimal for harmonic imaging; the second category may be more easily applied to harmonic imaging. However, inter-beam interference represents an issue. To overcome these shortcomings and exploit the benefit of combining harmonic imaging and high data acquisition rate, a new approach has been recently presented which relies on orthogonal frequency division multiplexing (OFDM) to perform parallel beamforming in transmission. In this paper, parallel transmit beamforming using OFDM is implemented for the first time on an ultrasound scanner. An advanced open platform for ultrasound research is used to investigate the axial resolution and interbeam interference achievable with parallel transmit beamforming using OFDM. Both fundamental and second-harmonic imaging modalities have been considered. Results show that, for fundamental imaging, axial resolution in the order of 2 mm can be achieved in combination with interbeam interference in the order of-30 dB. For second-harmonic imaging, axial resolution in the order of 1 mm can be achieved in combination with interbeam interference in the order of-35 dB.

Several studies on the propagation velocity of pressure wave fields through ultrasound contrast agents (UCAs) have been reported in the literature. However, the variation of propagation velocity between the fundamental and the second harmonic component generated during the propagation of ultrasound through UCAs has, to our knowledge, not been studied yet. To this scope, dedicated transmission and backscattering measurements of pressure wave fields propagating through SonoVue and Definity contrast agents, are analyzed. Results show the occurrence of a cumulative delay between the time signals related to the second harmonic and fundamental component, suggesting a smaller propagation velocity for the second harmonic as compared to the fundamental component. Moreover, this time delay increases with increasing UCA concentration and propagation path length of ultrasound trough microbubbles, depends on mechanical index and frequency, and, most importantly, is not observed in the absence of UCAs. These results may be relevant to contrast-enhanced ultrasonography, opening up to new possibilities to increase contrast-to-tissue ratios and to quantify UCA concentrations

Nonlinear ultrasound is important in medical diagnostics because imaging of the higher harmonics improves resolution and reduces scattering artifacts. Second harmonic imaging is currently standard, and higher harmonic imaging is under investigation. The efficient development of novel imaging modalities and equipment requires accurate simulations of nonlinear wave fields in large volumes of realistic (lossy, inhomogeneous) media. The Iterative Nonlinear Contrast Source (INCS) method has been developed to deal with spatiotemporal domains measuring hundreds of wavelengths and periods. This full wave method considers the nonlinear term of the Westervelt equation as a nonlinear contrast source, and solves the equivalent integral equation via the Neumann iterative solution. Recently, the method has been extended with a contrast source that accounts for spatially varying attenuation. The current paper addresses the problem that the Neumann iterative solution converges badly for strong contrast sources. The remedy is linearization of the nonlinear contrast source, combined with application of more advanced methods for solving the resulting integral equation. Numerical results show that linearization in combination with a Bi-Conjugate Gradient Stabilized method allows the INCS method to deal with fairly strong, inhomogeneous attenuation, while the error due to the linearization can be eliminated by restarting the iterative scheme., IST/Imaging Science and Technology, Applied Sciences

Several studies on the propagation velocity of pressure wave fields through ultrasound contrast agents (UCAs) have been reported in the literature. However, the variation of propagation velocity between the fundamental and the second harmonic component generated during the propagation of ultrasound through UCAs has, to our knowledge, not been studied yet. To this scope, dedicated transmission and backscattering measurements of pressure wave fields propagating through SonoVue and Definity contrast agents, are analyzed. Results show the occurrence of a cumulative delay between the time signals related to the second harmonic and fundamental component, suggesting a smaller propagation velocity for the second harmonic as compared to the fundamental component. Moreover, this time delay increases with increasing UCA concentration and propagation path length of ultrasound trough microbubbles, depends on mechanical index and frequency, and, most importantly, is not observed in the absence of UCAs. These results may be relevant to contrast-enhanced ultrasonography, opening up to new possibilities to increase contrast-to-tissue ratios and to quantify UCA concentrations

Nonlinear ultrasound is important in medical diagnostics because imaging of the higher harmonics improves resolution and reduces scattering artifacts. Second harmonic imaging is currently standard, and higher harmonic imaging is under investigation. The efficient development of novel imaging modalities and equipment requires accurate simulations of nonlinear wave fields in large volumes of realistic (lossy, inhomogeneous) media. The Iterative Nonlinear Contrast Source (INCS) method has been developed to deal with spatiotemporal domains measuring hundreds of wavelengths and periods. This full wave method considers the nonlinear term of the Westervelt equation as a nonlinear contrast source, and solves the equivalent integral equation via the Neumann iterative solution. Recently, the method has been extended with a contrast source that accounts for spatially varying attenuation. The current paper addresses the problem that the Neumann iterative solution converges badly for strong contrast sources. The remedy is linearization of the nonlinear contrast source, combined with application of more advanced methods for solving the resulting integral equation. Numerical results show that linearization in combination with a Bi-Conjugate Gradient Stabilized method allows the INCS method to deal with fairly strong, inhomogeneous attenuation, while the error due to the linearization can be eliminated by restarting the iterative scheme., IST/Imaging Science and Technology, Applied Sciences

The design and optimization of medical ultrasound modalities require a method for modeling the propagation of pressure wave fields through biomedical tissue. This method needs to be capable of modeling various phenomena, e.g. nonlinear propagation, attenuation, and scattering caused by arbitrary inhomogeneities in the acoustic properties of the medium. The Iterative Nonlinear Contrast Source (INCS) method is a full wave method which makes use of a contrast source approach to model nonlinear propagation of ultrasound. Originally, the method was used to model nonlinear propagation in homogeneous nonlinear media with frequency power law attenuation. In this thesis, the basic steps of INCS are conserved and the method is extended to deal with spatially varying attenuation, coefficient of nonlinearity and speed of sound. The method developed uses a generalized form of the Westervelt equation which includes a spatially dependent coefficient of nonlinearity, speed of sound and relaxation function. The generalized Westervelt equation is recast into an integral equation and solved using three different iterative schemes: Neumann, Bi-CGSTAB and Steepest Descent. The performances of these schemes are analyzed and compared. Furthermore, as an example of a possible application of the method developed, a feasibility study of a new beam forming technique, i.e. parallel transmit beam forming using orthogonal frequency division multiplexing applied to harmonic imaging, is performed. Numerical studies show the capability of this technique to reduce the presence of unwanted side-lobes and meanwhile increase the amplitude of the main beam as compared to standard parallel beam forming in reception. These improvements are expected to positively influence the signal to noise ratio and the achievable penetration depth of a given imaging system. A drawback of the technique proposed is a reduction of the axial resolution due to utilization of pulses with a narrower bandwidth. Finally, measur, Imaging Science & Technology, Applied Sciences

The Iterative Nonlinear Contrast Source (INCS) method is a full-wave method for the accurate computation of wide-angle, pulsed, nonlinear ultrasound fields appearing in, e.g., medical echoscopy. The method is based on the Westervelt equation and considers the occurring nonlinear term as a distributed contrast source that operates in a linear background medium. This formulation leads to an integral equation, which is solved in an iterative way. The original INCS method uses a Neumann scheme to successively approximate the nonlinear wave field in homogeneous, lossless, nonlinear media. To cope with attenuative and/or inhomogeneous nonlinear media, additional contrast sources may be introduced. Since these deteriorate the convergence rate of the Neumann scheme, more advanced iterative solution schemes like Bi-CGSTAB are required. To overcome the difficulty that such schemes only apply to linear integral equations, the nonlinear contrast source is linearized, at the cost of a significant systematic error in the fourth and higher harmonics. In this paper, a strategy is proposed in which the relevant iterative solution scheme is restarted with an updated version of the linearized contrast source. Results demonstrate the effectiveness of this strategy in eliminating the systematic error. In addition, it is shown that the same approach also improves the convergence rate in case of nonlinear propagation in media with attenuation., Imaging Science and Technology, Applied Sciences

The Iterative Nonlinear Contrast Source (INCS) method is a full-wave method for the accurate computation of wide-angle, pulsed, nonlinear ultrasound fields appearing in, e.g., medical echoscopy. The method is based on the Westervelt equation and considers the occurring nonlinear term as a distributed contrast source that operates in a linear background medium. This formulation leads to an integral equation, which is solved in an iterative way. The original INCS method uses a Neumann scheme to successively approximate the nonlinear wave field in homogeneous, lossless, nonlinear media. To cope with attenuative and/or inhomogeneous nonlinear media, additional contrast sources may be introduced. Since these deteriorate the convergence rate of the Neumann scheme, more advanced iterative solution schemes like Bi-CGSTAB are required. To overcome the difficulty that such schemes only apply to linear integral equations, the nonlinear contrast source is linearized, at the cost of a significant systematic error in the fourth and higher harmonics. In this paper, a strategy is proposed in which the relevant iterative solution scheme is restarted with an updated version of the linearized contrast source. Results demonstrate the effectiveness of this strategy in eliminating the systematic error. In addition, it is shown that the same approach also improves the convergence rate in case of nonlinear propagation in media with attenuation., Imaging Science and Technology, Applied Sciences

In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse-echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field., Electrical Engineering, Mathematics and Computer Science

Experimental data reveals that attenuation is an important phenomenon in medical ultrasound. Attenuation is particularly important for medical applications based on nonlinear acoustics, since higher harmonics experience higher attenuation than the fundamental. Here, a method is presented to accurately solve the wave equation for nonlinear acoustic media with spatially inhomogeneous attenuation. Losses are modeled by a spatially dependent compliance relaxation function, which is included in the Westervelt equation. Introduction of absorption in the form of a causal relaxation function automatically results in the appearance of dispersion. The appearance of inhomogeneities implies the presence of a spatially inhomogeneous contrast source in the presented full-wave method leading to inclusion of forward and backward scattering. The contrast source problem is solved iteratively using a Neumann scheme, similar to the iterative nonlinear contrast source (INCS) method. The presented method is directionally independent and capable of dealing with weakly to moderately nonlinear, large scale, three-dimensional wave fields occurring in diagnostic ultrasound. Convergence of the method has been investigated and results for homogeneous, lossy, linear media show full agreement with the exact results. Moreover, the performance of the method is demonstrated through simulations involving steered and unsteered beams in nonlinear media with spatially homogeneous and inhomogeneous attenuation., IST/Imaging Science and Technology, Applied Sciences

In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse-echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field., Electrical Engineering, Mathematics and Computer Science

Experimental data reveals that attenuation is an important phenomenon in medical ultrasound. Attenuation is particularly important for medical applications based on nonlinear acoustics, since higher harmonics experience higher attenuation than the fundamental. Here, a method is presented to accurately solve the wave equation for nonlinear acoustic media with spatially inhomogeneous attenuation. Losses are modeled by a spatially dependent compliance relaxation function, which is included in the Westervelt equation. Introduction of absorption in the form of a causal relaxation function automatically results in the appearance of dispersion. The appearance of inhomogeneities implies the presence of a spatially inhomogeneous contrast source in the presented full-wave method leading to inclusion of forward and backward scattering. The contrast source problem is solved iteratively using a Neumann scheme, similar to the iterative nonlinear contrast source (INCS) method. The presented method is directionally independent and capable of dealing with weakly to moderately nonlinear, large scale, three-dimensional wave fields occurring in diagnostic ultrasound. Convergence of the method has been investigated and results for homogeneous, lossy, linear media show full agreement with the exact results. Moreover, the performance of the method is demonstrated through simulations involving steered and unsteered beams in nonlinear media with spatially homogeneous and inhomogeneous attenuation., IST/Imaging Science and Technology, Applied Sciences

The refraction and scattering of nonlinear acoustic waves play an important role in the realistic application of medical ultrasound. One cause of these effects is the tissue dependence of the nonlinear medium behavior. A method that is able to model those effects is essential for the design of transducers for novel ultrasound modalities. Starting from the Westervelt equation, nonlinear pressure wave fields can be modeled via a contrast source formulation, as has been done with the INCS method. An extension of this method will be presented that can handle inhomogeneities in the coefficient of nonlinearity. The contrast source formulation results in an integral equation, which is solved iteratively using a Neumann scheme. The convergence of this scheme has been investigatedfor relevant media (e.g., blood, brain, and liver). Further, as an example, the method has been applied to compute the 1D nonlinear acoustic wave field in an inhomogeneous medium insonified by a 1 MHz Gaussian pulse propagatingup to 100 mm. The results show that the method is able to predict the propagation and the scattering effects of nonlinear acoustic waves in media with inhomogeneities in the coefficient of nonlinearity. This motivates a similar extension ofthe 3D INCS method., IST/Imaging Science and Technology, Applied Sciences

The refraction and scattering of nonlinear acoustic waves play an important role in the realistic application of medical ultrasound. One cause of these effects is the tissue dependence of the nonlinear medium behavior. A method that is able to model those effects is essential for the design of transducers for novel ultrasound modalities. Starting from the Westervelt equation, nonlinear pressure wave fields can be modeled via a contrast source formulation, as has been done with the INCS method. An extension of this method will be presented that can handle inhomogeneities in the coefficient of nonlinearity. The contrast source formulation results in an integral equation, which is solved iteratively using a Neumann scheme. The convergence of this scheme has been investigatedfor relevant media (e.g., blood, brain, and liver). Further, as an example, the method has been applied to compute the 1D nonlinear acoustic wave field in an inhomogeneous medium insonified by a 1 MHz Gaussian pulse propagatingup to 100 mm. The results show that the method is able to predict the propagation and the scattering effects of nonlinear acoustic waves in media with inhomogeneities in the coefficient of nonlinearity. This motivates a similar extension ofthe 3D INCS method., IST/Imaging Science and Technology, Applied Sciences