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Despite being the solid tumor with the highest incidence in western men, prostate cancer (PCa) still lacks reliable imaging solutions that can overcome the need for systematic biopsies. Dynamic contrast-enhanced ultrasound imaging (DCE-US) allows us to quantitatively characterize the vascular bed in the prostate, due to its ability to visualize an intravenously administered bolus of contrast agents. Previous research has demonstrated that DCE-US parameters related to the vascular architecture are useful markers for the localization of PCa lesions. In this paper, we propose a novel method to assess the convective dispersion (D) and velocity (v) of the contrast bolus spreading through the prostate from three-dimensional (3D) DCE-US recordings. By assuming that D and v are locally constant, we solve the convective-dispersion equation by minimizing the corresponding regularized least-squares problem. 3D multiparametric maps of D and v were compared with 3D histopathology retrieved from the radical prostatectomy specimens of six patients. With a pixel-wise area under the receiver operating characteristic curve of 0.72 and 0.80, respectively, the method shows diagnostic value for the localization of PCa.

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.

OBJECTIVE: Beneficial effects, including improved muscle strength and power performance, have been observed during vibration exercise (VE) and partially ascribed to a specific reflex mechanism referred to as Tonic vibration reflex (TVR). TVR involves motor unit (MU) activation synchronized and un-synchronized with the vibration cycle; this suggests VE to alter the temporal MU recruitment strategy. However, the effects of VE on MU recruitment remain poorly understood. This study aims to elucidate the influence of VE on MU recruitment indirectly, by investigating the effects of low-intensity VE on muscle activation. APPROACH: Twenty volunteers performed isometric contractions on the biceps brachii of the right arm at a baseline (low) force equal to 30% of the maximum voluntary contraction without vibration (control) and with vibration at 20, 30, 40, and 55 Hz. Three vibration amplitudes were employed at 12.5%, 25%, and 50% of the baseline. Mean muscle-fiber conduction velocity (mCV), mean frequency (MF), and root mean square (RMS) value were estimated from surface electromyography as indicators of the alteration in MU recruitment strategies. MAIN RESULTS: The mCV estimates during VE were significantly (p < 0.05) higher compared to the control condition. Furthermore, six VE conditions produced significantly larger RMS values compared to control condition. The estimated MF did not show any consistent trend. SIGNIFICANCE: These results suggest that vibration superimposed on low-level isometric contraction alters the MU recruitment strategy, activating larger and faster MUs.

Purpose: Uterine activity plays a key role in reproduction, and altered patterns of uterine contractility have been associated with important physiopathological conditions, such as subfertility, dysmenorrhea, and endometriosis. However, there is currently no method to objectively quantify uterine contractility outside pregnancy without interfering with the spontaneous contraction pattern. Transabdominal electrohysterography has great potential as a clinical tool to characterize noninvasively uterine activity, but results of this technique in nonpregnant women are poorly documented. The purpose of this study is to investigate the feasibility of transabdominal electrohysterography in nonpregnant women. Methods: Longitudinal measurements were performed on 22 healthy women in 4 representative phases of the menstrual cycle. Twelve electrohysterogram-based indicators previously validated in pregnancy have been estimated and compared in the 4 phases of the cycle. Using the Tukey honest significance test, significant differences were defined for P values below.05. Results: Half of the selected electrohysterogram-based indicators showed significant differences between menses and at least 1 of the other 3 phases, that is the luteal phase. Conclusion: Our results suggest transabdominal electrohysterography to be feasible for analysis of uterine activity in nonpregnant women. Due to the lack of a golden standard, this feasibility study is indirectly validated based on physiological observations. However, these promising results motivate further research aiming at evaluating electrohysterography as a method to improve understanding and management of dysfunctions (possibly) related to altered uterine contractility, such as infertility, endometriosis, and dysmenorrhea.

Periodic motion artifacts affect photoplethysmography (PPG) signals in activities of daily living (ADL), cardiopulmonary exercise testing (CPX), and cardiopulmonary resuscitation (CPR). This hampers measurement of interbeat intervals (IBIs) and oxygen saturation (SpO2 ). Our objective was to develop a generic algorithm to remove periodic motion artifacts, recovering artifact-reduced PPG signals for beat-to-beat analysis. Methods: The algorithm was retrospectively evaluated on forehead PPG signals measured while walking on a treadmill. The step rate was tracked in a motion reference signal via a second-order generalized integrator with a frequency-locked loop. Two reference signals were compared: sensor motion relative to the skin (Δx[n]) measured via self-mixing interferometry and head motion (av[n] ) measured via accelerometry. The step rate was used in a quadrature harmonic model to estimate the artifacts. Quadrature components need only two coefficients per frequency leading to a short filter and prevent undesired frequency-shifted components in the artifact estimate. Subtracting the estimate from the measured signal reduced the artifacts. Results: Compared to Δx[n] , av[n] had a better signal-to-noise ratio and more consistently contained a component at the step rate. Artifact reduction was effective for distinct step rate and pulse rate, since the artifact-reduced signals provided more stable IBI and SpO 2 measurements. Conclusion: Accelerometry provided a more reliable motion reference signal. The proposed algorithm can be of significance for monitoring in ADL, CPX, or CPR, by providing artifact-reduced PPG signals for improved IBI and SpO 2 measurements during periodic motion.

Estimation of soft tissue elasticity is of interest in several clinical applications. For instance, tumors and fibrotic lesions are notoriously stiff compared with benign tissue. A fully quantitative measure of lesion stiffness can be obtained by shear wave (SW) elastography. This method uses an acoustic radiation force to produce laterally propagating SWs that can be tracked to obtain the velocity, which in turn is related to Young's modulus. However, not only elasticity, but also viscosity plays an important role in the propagation process of SWs. In fact, viscosity itself is a parameter of diagnostic value for the detection and characterization of malignant lesions. In this paper, we describe a new method that enables imaging viscosity from SW elastography by local model-based system identification. By testing the method on simulated data sets and performing in vitro experiments, we show that the ability of the proposed technique to generate parametric maps of the viscoelastic material properties from SW measurements, opening up new possibilities for noninvasive tissue characterization.

OBJECTIVE: Doppler ultrasound (US) is the most commonly applied method to measure the fetal heart rate (fHR). When the fetal heart is not properly located within the ultrasonic beam, fHR measurements often fail. As a consequence, clinical staff need to reposition the US transducer on the maternal abdomen, which can be a time consuming and tedious task.APPROACH: In this article, a method is presented to aid clinicians with the positioning of the US transducer to produce robust fHR measurements. A maximum likelihood estimation (MLE) algorithm is developed, which provides information on fetal heart location using the power of the Doppler signals received in the individual elements of a standard US transducer for fHR recordings. The performance of the algorithm is evaluated with simulations and in vitro experiments performed on a beating-heart setup.MAIN RESULTS: Both the experiments and the simulations show that the heart location can be accurately determined with an error of less than 7 mm within the measurement volume of the employed US transducer.SIGNIFICANCE: The results show that the developed algorithm can be used to provide accurate feedback on fetal heart location for improved positioning of the US transducer, which may lead to improved measurements of the fHR.

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.

Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into ca

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.

BACKGROUND: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies.METHODS/DESIGN: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols.DISCUSSION: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantifica

Objective: Observational cohort study which aimed to explore the potential of electrohysterogram (EHG) analysis for detecting a uterine rupture during trial of labor after cesarean. The EHG propagation characteristics surrounding the uterine scar of six patients with a previous cesarean section were compared to a control group of five patients without a scarred uterus. Methods: The EHG was recorded during the first stage of labor using a high-resolution 64- channel electrode grid positioned on the maternal abdomen across the cesarean scar. Based on simulations, the inter-channel correlation and propagation direction were adopted as EHG parameters for evaluating possible disruption of electrical propagation by the uterine scar. Results: No significant differences in inter-channel correlation or propagation direction were observed between the group of patients with an intact uterine scar and the control group. A strong predominance of vertical propagation was observed in one case, in which scar rupture occurred. Conclusions: The results support unaffected propagation of electrical activity through the intact uterine scar tissue suggesting that changes in the EHG might only occur in case of rupture.