Dehazing Ultrasound using Diffusion Models.

Echocardiography has been a prominent tool for the diagnosis of cardiac disease. However, these diagnoses can be heavily impeded by poor image quality. Acoustic clutter emerges due to multipath reflections imposed by layers of skin, subcutaneous fat, and intercostal muscle between the transducer and heart. As a result, haze and other noise artifacts pose a real challenge to cardiac ultrasound imaging. In many cases, especially with difficult-to-image patients such as patients with obesity, a diagnosis from B-Mode ultrasound imaging is effectively rendered unusable, forcing sonographers to resort to contrast-enhanced ultrasound examinations or refer patients to other imaging modalities. Tissue harmonic imaging has been a popular approach to combat haze, but in severe cases is still heavily impacted by haze. Alternatively, denoising algorithms are typically unable to remove highly structured and correlated noise, such as haze. It remains a challenge to accurately describe the statistical properties of structured haze, and develop an inference method to subsequently remove it. Diffusion models have emerged as powerful generative models and have shown their effectiveness in a variety of inverse problems. In this work, we present a joint posterior sampling framework that combines two separate diffusion models to model the distribution of both clean ultrasound and haze in an unsupervised manner. Furthermore, we demonstrate techniques for effectively training diffusion models on radio-frequency ultrasound data and highlight the advantages over image data. Experiments on both in-vitro and in-vivo cardiac datasets show that the proposed dehazing method effectively removes haze while preserving signals from weakly reflected tissue.

Specific detection of Treponema pallidum in clinical samples: validation of a qPCR assay combining two genomic targets.

OBJECTIVES: We evaluated a real-time quantitative PCR (qPCR) for detection of the Treponema pallidum (TP) genome in clinical samples through simultaneous detection of two genomic targets. METHODS: We performed qPCR with TaqMan technology using two TP genes, polA and tpp47, as targets, with an internal positive control. The qPCR assay was compared with syphilis diagnosis based on a combination of clinical examination, serological results and inhouse nested PCR (nPCR). Samples were analysed at the National Reference Center for STIs at Cochin Hospital in Paris. RESULTS: In total, from October 2010 to December 2016, 320 documented clinical samples (mucosal and cutaneous swabs) were collected from patients with or without syphilis attending STI centres in France. The qPCR had an overall sensitivity of 89% (95% CI 85.1% to 92.1%), a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 88% (95% CI 84.3% to 91.5%). The agreement between qPCR and nPCR results was 94% (κ=0.88, 95% CI 0.83 to 0.93). Calibration of the qPCR assay, by cloning both the polA and tpp47 genes, defined the detection threshold as 1 copy/µL of DNA elution. CONCLUSIONS: We validated a new qPCR for detecting the TP genome in clinical samples with excellent sensitivity and specificity. The cloning of polA and tpp47 genes for calibration would be interesting in the evaluation of bacterial loads in samples.

Surveillance of Antibiotic Resistance Genes in Treponema Pallidum Subspecies Pallidum from Patients with Early Syphilis in France.

Benzathine penicillin G (BPG) is the reference treatment for early syphilis, but shortages have recently been reported, highlighting a need for the validation of alternative treatments. The aim of this study was to evaluate the genomic resistance of Treponema pallidum subspecies pallidum (TPA) to macrolides and doxycycline in France. Swabs from genital, anal, oral and cutaneous lesions were obtained from 146 patients with early syphilis in France. They were screened for mutations conferring resistance to macrolides and doxycycline by nested PCR and sequencing. Resistance to macrolides was detected in 85% of the isolates, but no point mutations conferring doxycycline resistance were detected. These findings confirm that, in France, resistance to macrolides is widespread. Moreover, we confirmed the absence of genomic resistance to doxycycline in the TPA strains. Therefore, doxycycline could be safely recommended as an alternative to BPG for the treatment of early syphilis.

Using redundancy of round-trip ultrasound signal for non-continuous arrays: Application to gap and blockage compensation.

In ultrasound imaging, an array of elements is used to image a medium. If part of the array is blocked by an obstacle, or if the array is made from several sub-arrays separated by a gap, grating lobes appear and the image is degraded. The grating lobes are caused by missing spatial frequencies, corresponding to the blocked or non-existing elements. However, in an active imaging system, where elements are used both for transmitting and receiving, the round trip signal is redundant: different pairs of transmit and receive elements carry similar information. It is shown here that, if the gaps are smaller than the active sub-apertures, this redundancy can be used to compensate for the missing signals and recover full resolution. Three algorithms are proposed: one is based on a synthetic aperture method, a second one uses dual-apodization beamforming, and the third one is a radio frequency (RF) data based deconvolution. The algorithms are evaluated on simulated and experimental data sets. An application could be imaging through ribs with a large aperture.

Time domain compressive beam forming of ultrasound signals.

Ultrasound imaging is a wide spread technique used in medical imaging as well as in non-destructive testing. The technique offers many advantages such as real-time imaging, good resolution, prompt acquisition, ease of use, and low cost compared to other techniques such as x-ray imaging. However, the maximum frame rate achievable is limited as several beams must be emitted to compute a single image. For each emitted beam, one must wait for the wave to propagate back and forth, thus imposing a limit to the frame rate. Several attempts have been made to use less beams while maintaining image quality. Although efficiently increasing the frame rate, these techniques still use several transmit beams. Compressive Sensing (CS), a universal data completion scheme based on convex optimization, has been successfully applied to a number of imaging modalities over the past few years. Using a priori knowledge of the signal, it can compute an image using less data allowing for shorter acquisition times. In this paper, it is shown that a valid CS framework can be derived from ultrasound propagation theory, and that this framework can be used to compute images of scatterers using only one plane wave as a transmit beam.

Noninvasive assessment of liver fibrosis using ultrasound-based shear wave measurement and comparison to magnetic resonance elastography.

OBJECTIVES: Magnetic resonance elastography (MRE) has excellent performance in detecting liver fibrosis and is becoming an alternative to liver biopsy in clinical practice. Ultrasound techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force also have shown promising results for liver fibrosis staging. The objective of this study was to compare ultrasound-based shear wave measurement to MRE. METHODS: In this study, 50 patients (28 female and 22 male; age range, 19-81 years) undergoing liver MRE examinations were studied with an ultrasound scanner modified with shear wave measurement functionality. For each patient, 27 shear wave speed measurements were obtained at various locations in the liver parenchyma away from major vessels. The median shear wave speed from all measurements was used to calculate a representative shear modulus (µ) for each patient. Magnetic resonance elastographic data processing was done by a single analyst blinded to the ultrasound measurement results. RESULTS: Ultrasound and MRE measurements were correlated (r = 0.86; P < .001). Receiver operating characteristic (ROC) analysis was applied to the ultrasound measurement results with the MRE diagnosis as the "ground truth." The area under the ROC curve for separating patients with minimum fibrosis (defined as µ(MRE) ≤2.9 kPa) was 0.89 (95% confidence interval, 0.77-0.95), and the area under the ROC curve for separating patients with advanced fibrosis (defined as µ(MRE) ≥5.0 kPa) was 0.96 (95% confidence interval, 0.87-0.99). CONCLUSIONS: Results indicate that the ultrasound-based shear wave measurement correlates with MRE and is a promising method for liver fibrosis staging.

Development of oil-in-gelatin phantoms for viscoelasticity measurement in ultrasound shear wave elastography.

Because tissues consist of solid and fluid materials, their mechanical properties should be characterized in terms of both elasticity and viscosity. Although the elastic properties of tissue-mimicking phantoms have been extensively studied and well characterized in commercially available phantoms, their viscous properties have not been fully investigated. In this article, a set of 14 tissue-mimicking phantoms with different concentrations of gelatin and castor oil were fabricated and characterized in terms of acoustic and viscoelastic properties. The results indicate that adding castor oil to gelatin phantoms decreases shear modulus, but increases shear wave dispersion. For 3% gelatin phantoms containing 0%, 10%, 20% and 40% oil, the measured shear moduli are 2.01 ± 0.26, 1.68 ± 0.25, 1.10 ± 0.22 and 0.88 ± 0.17 kPa, and the Voigt-model coupled shear viscosities are 0.60 ± 0.11, 0.89 ± 0.07, 1.05 ± 0.11 and 1.06 ± 0.13 Pa·s, respectively. The results also confirm that increasing the gelatin concentration increases shear modulus. For phantoms containing 3%, 4%, 5%, 6% and 7% gelatin, the measured shear moduli are 2.01 ± 0.26, 3.10 ± 0.34, 4.18 ± 0.84, 8.05 ± 1.00 and 10.24 ± 1.80 kPa at 0% oil and 1.10 ± 0.22, 1.97 ± 0.20, 3.13 ± 0.63, 4.60 ± 0.60 and 8.43 ± 1.39 kPa at 20% oil, respectively. The phantom recipe developed in this study can be used in validating ultrasound shear wave elastography techniques for soft tissues.

ANT-VDAC1 interaction is direct and depends on ANT isoform conformation in vitro.

The voltage-dependent anion channel (VDAC) and the adenine nucleotide translocase (ANT) have central roles in mitochondrial functions such as nucleotides transport and cell death. The interaction between VDAC, an outer mitochondrial membrane protein and ANT, an inner membrane protein, was studied in isolated mitochondria and in vitro. Both proteins were isolated from various mitochondrial sources and reconstituted in vitro using a biomimetic system composed of recombinant human VDAC isoform 1 (rhVDAC1) immobilized on a surface plasmon resonance (SPR) sensor chip surface. Two enriched-preparations of (H)ANT (ANT from heart, mainly ANT1) and (L)ANT (ANT from liver, mainly ANT2) isoforms interacted differently with rhVDAC1. Moreover, the pharmacological ANT inhibitors atractyloside and bongkrekic acid modulated this interaction. Thus, ANT-VDAC interaction depends both on ANT isoform identity and on the conformation of ANT.

In vivo three-dimensional photoacoustic imaging based on a clinical matrix array ultrasound probe.

We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.

Spatio-temporal invariants of the time reversal operator.

The decomposition of the time reversal operator, known by the French acronym DORT, is a technique to extract point scatterers' monochromatic Green's functions from a medium. It is used to detect, locate, and focus on scatterers in various domains such as underwater acoustics, medical ultrasound, and nondestructive evaluation. A limitation of the method arises from its single-frequency nature, when the signals used in acoustics are often broadband. Reconstruction of the broadband Green's functions from the single-frequency Green's functions can be very difficult when numerous scatterers are present in the medium. Moreover, the method does not take advantage of the axial resolution associated with broadband signals. Time domain methods are investigated here as an answer to these problems. It is shown that the time reversal operator in the time domain takes the form of a tensor. The properties of the invariants are discussed. It is shown they do not have all the expected properties. Another method is proposed that requires a priori information on the medium.

The prolate spheroidal wave functions as invariants of the time reversal operator for an extended scatterer in the Fraunhofer approximation.

The decomposition of the time reversal operator, known by the French acronym DORT, is widely used to detect, locate, and focus on scatterers in various domains such as underwater acoustics, medical ultrasound, and nondestructive evaluation. In the case of point-scatterers, the theory is well understood: The number of nonzero eigenvalues is equal to the number of scatterers, and the eigenvectors correspond to the scatterers Green's function. In the case of extended objects, however, the formalism is not as simple. It is shown here that, in the Fraunhofer approximation, analytical solutions can be found and that the solutions are functions called prolate spheroidal wave-functions. These functions have been studied in information theory as a basis of band-limited and time-limited signals. They also arise in optics. The theoretical solutions are compared to simulation results. Most importantly, the intuition that for an extended objects, the number of nonzero eigenvalues is proportional to the number of resolution cell in the object is justified. The case of three-dimensional objects imaged by a two-dimensional array is also dealt with. Comparison with previous solutions is made, and an application to super-resolution of scatterers is presented.

Green's function estimation in speckle using the decomposition of the time reversal operator: application to aberration correction in medical imaging.

The FDORT method (French acronym for decomposition of the time reversal operator using focused beams) is a time reversal based method that can detect point scatterers in a heterogeneous medium and extract their Green's function. It is particularly useful when focusing in a heterogeneous medium. This paper generalizes the theory of the FDORT method to random media (speckle), and shows that it is possible to extract Green's functions from the speckle signal using this method. Therefore it is possible to achieve a good focusing even if no point scatterers are present. Moreover, a link is made between FDORT and the Van Cittert-Zernike theorem. It is deduced from this interpretation that the normalized first eigenvalue of the focused time reversal operator is a well-known focusing criterion. The concept of an equivalent virtual object is introduced that allows the random problem to be replaced by an equivalent deterministic problem and leads to an intuitive understanding of FDORT in speckle. Applications to aberration correction are presented. The reduction of the variance of the Green's function estimate is discussed. Finally, it is shown that the method works well in the presence of strong interfering scatterers.

The time-reversal operator with virtual transducers: application to far-field aberration correction.

The decomposition of the time-reversal operator (DORT) is a detection and focusing technique using an array of transmit receive transducers. It can extract Green's functions of scatterers in a medium. A variant consists in transmitting focused beams (FDORT). It is shown here that the FDORT method can be interpreted as the decomposition of a time-reversal operator between an array of virtual transducers located at the transmit beams' foci and the physical array. The receive singular vectors correspond to scatterers' Green's functions expressed in the physical array while the transmit singular vectors correspond to Green's functions expressed in the virtual array. The position of the virtual array can be changed by varying the position of the foci, thus offering different points of view. Parameters and performance of some transmit schemes are discussed. Appropriately positioning the virtual transducers can simplify some problems. One application is measuring and correcting aberration in the case of a far-field phase screen model. Placing the virtual transducers near the phase screen transforms the problem in a simpler near-field phase screen problem.