Pulse-echo ultrasound attenuation tomography.

We present the first fully two-dimensional attenuation imaging technique developed for pulse-echo ultrasound systems. Unlike state-of-the-art techniques, which use line-by-line acquisitions, our method uses steered emissions to constrain attenuation values at each location with multiple crossing wave paths, essential to resolve the spatial variations of this tissue property.At every location, we compute normalized cross-correlations between the beamformed images that are obtained from emissions at different steering angles.

Fluorescence lifetime imaging and phasor analysis of intracellular porphyrinic photosensitizers applied with different polymeric formulations.

The fluorescence lifetime of a porphyrinic photosensitizer (PS) is an important parameter to assess the aggregation state of the PS even in complex biological environments. Aggregation-induced quenching of the PS can significantly reduce the yield of singlet oxygen generation and thus its efficiency as a medical drug in photodynamic therapy (PDT) of diseased tissues. Hydrophobicity and the tendency to form aggregates pose challenges on the development of efficient PSs and often require carrier systems.

Real-time OCT feedback-controlled RPE photodisruption in ex vivo porcine eyes using 8 microsecond laser pulses.

Selective retinal pigment epithelium (RPE) photodisruption requires reliable real-time feedback dosimetry (RFD) to prevent unwanted overexposure. In this study, optical coherence tomography (OCT) based RFD was investigated in ex vivo porcine eyes exposed to laser pulses of 8 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm, radiant exposure: 247 to 1975 mJ/µm). For RFD, fringe washouts in time-resolved OCT M-scans (central wavelength: 870 nm, scan rate: 85 kHz) were compared to an RPE cell viability assay.

Wide-field time-of-flight measurements of highly scattering media.

We present a setup that makes use of a time-resolved single-photon camera to determine the scattering parameters of media. The measurement is realized in a non-contact way, both for the illumination laser and the detection. By fitting the time-of-flight acquired distributions at different spatial positions with the diffusion equation, we retrieve the reduced scattering coefficients of a highly diffusive isotropic reference media for wavelengths in the range from 540 to 840 nm.

First-in-human diagnostic study of hepatic steatosis with computed ultrasound tomography in echo mode.

Background: Non-alcoholic fatty liver disease is rapidly emerging as the leading global cause of chronic liver disease. Efficient disease management requires low-cost, non-invasive techniques for diagnosing hepatic steatosis accurately. Here, we propose quantifying liver speed of sound (SoS) with computed ultrasound tomography in echo mode (CUTE), a recently developed ultrasound imaging modality adapted to clinical pulse-echo systems.

The Cilialyzer - A freely available open-source software for the analysis of mucociliary activity in respiratory cells.

Background And Objective: Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing a defective ciliary structure, which predominantly leads to an impaired mucociliary clearance and associated airway disease. As there is currently no single diagnostic gold standard test, PCD is diagnosed by a combination of several methods comprising genetic testing and the examination of the ciliary structure and function. Among the approved diagnostic methods, only high-speed video microscopy (HSVM) allows to directly observe the ciliary motion and therefore, to directly assess ciliary function.

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques.

Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains ().

Excluding Echo Shift Noise in Real-Time Pulse-Echo Speed-of-Sound Imaging.

Computed ultrasound tomography in echo mode (CUTE) allows real-time imaging of the tissue speed of sound (SoS) using handheld ultrasound. The SoS is retrieved by inverting a forward model that relates the spatial distribution of the tissue SoS to echo shift maps detected between varying transmit and receive angles. Despite promising results, in vivo SoS maps often show artifacts due to elevated noise in echo shift maps.

Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium.

Optical microsurgery confined to the retinal pigment epithelium (RPE) requires locally optimized laser parameters and reliable real-time feedback dosimetry (RFD) to prevent unwanted neuroretinal overexposure. This study aimed to compare pulses of different durations and application modes (single, ramp, burst). Moreover, optical coherence tomography (OCT)-based RFD was investigated in an ex vivo experiment, utilizing nine porcine eyes that were exposed to laser pulses of 8, 12, 16 and 20 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm, radiant exposure: 247 to 1975 mJ/µm).

Effect of Combined Hypertonic Saline and Salbutamol on Ciliary Beating Frequency and Mucociliary Transport in Human Nasal Epithelial Cells of Healthy Volunteers and Patients with Cystic Fibrosis.

Inhalation of hypertonic saline (HS) is standard of care in patients with cystic fibrosis (CF). However, it is unclear if adding salbutamol has-besides bronchodilation-further benefits, for example, on the mucociliary clearance. We assessed this by measuring the ciliary beating frequency (CBF) and the mucociliary transport rate (MCT) in nasal epithelial cells (NECs) of healthy volunteers and patients with CF.

Pulse-echo speed-of-sound imaging using convex probes.

Computed ultrasound tomography in echo mode (CUTE) is a new ultrasound (US)-based medical imaging modality with promise for diagnosing various types of disease based on the tissue's speed of sound (SoS). It is developed for conventional pulse-echo US using handheld probes and can thus be implemented in state-of-the-art medical US systems. One promising application is the quantification of the liver fat fraction in fatty liver disease.

Machine learning enabled multiple illumination quantitative optoacoustic oximetry imaging in humans.

Optoacoustic (OA) imaging is a promising modality for quantifying blood oxygen saturation (sO) in various biomedical applications - in diagnosis, monitoring of organ function, or even tumor treatment planning. We present an accurate and practically feasible real-time capable method for quantitative imaging of sO based on combining multispectral (MS) and multiple illumination (MI) OA imaging with learned spectral decoloring (LSD). For this purpose we developed a hybrid real-time MI MS OA imaging setup with ultrasound (US) imaging capability; we trained gradient boosting machines on MI spectrally colored absorbed energy spectra generated by generic Monte Carlo simulations and used the trained models to estimate sO on real OA measurements.

A quantitative interspecies comparison of the respiratory mucociliary clearance mechanism.

Collectively coordinated ciliary activity propels the airway mucus, which lines the luminal surface of the vertebrate respiratory system, in cranial direction. Our contemporary understanding on how the quantitative characteristics of the metachronal wave field determines the resulting mucociliary transport is still limited, partly due to the sparse availability of quantitative observational data. We employed high-speed video reflection microscopy to image and quantitatively characterize the metachronal wave field as well as the mucociliary transport in excised bovine, porcine, ovine, lapine, turkey and ostrich samples.

Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy.

Purpose: Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases such as age-related macular degeneration. Herein, selective microsecond laser irradiation targeting RPE cells was used for minimally invasive, large-area RPE removal in preparation for delivery of retinal cell therapeutics.

Methods: Ten rabbit eyes were exposed to laser pulses 8, 12, 16, and 20 µs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 µm²).

Backscattering polarimetric imaging of the human brain to determine the orientation and degree of alignment of nerve fiber bundles.

The nerve fiber bundles constitutive of the white matter in the brain are organized in such a way that they exhibit a certain degree of structural anisotropy and birefringence. The birefringence exhibited by such aligned fibrous tissue is known to be extremely sensitive to small pathological alterations. Indeed, highly aligned anisotropic fibers exhibit higher birefringence than structures with weaker alignment and anisotropy, such as cancerous tissue.

Multiple illumination learned spectral decoloring for quantitative optoacoustic oximetry imaging.

Significance: Quantitative measurement of blood oxygen saturation (sO2) with optoacoustic (OA) imaging is one of the most sought after goals of quantitative OA imaging research due to its wide range of biomedical applications.

Aim: A method for accurate and applicable real-time quantification of local sO2 with OA imaging.

Approach: We combine multiple illumination (MI) sensing with learned spectral decoloring (LSD).

Multi-scale alignment of respiratory cilia and its relation to mucociliary function.

The tracheobronchial tree is lined by a mucociliary epithelium containing millions of multiciliated cells. Their integrated oscillatory activity continuously propels an overlying pollution-protecting mucus layer in cranial direction, leading to mucociliary clearance - the primary defence mechanism of the airways. Mucociliary transport is commonly thought to co-emerge with the collective ciliary motion pattern under appropriate geometrical and rheological conditions.

Bayesian Approach for a Robust Speed-of-Sound Reconstruction Using Pulse-Echo Ultrasound.

Computed ultrasound tomography in echo mode (CUTE) is a promising ultrasound (US) based multi-modal technique that allows to image the spatial distribution of speed of sound (SoS) inside tissue using hand-held pulse-echo US. It is based on measuring the phase shift of echoes when detected under varying steering angles. The SoS is then reconstructed using a regularized inversion of a forward model that describes the relation between the SoS and echo phase shift.

A novel technique for laser-assisted revascularization: an in vitro pilot study.

The common limitation of surgical revascularization procedures for severe tissue ischemia due to cardiovascular diseases is the need to interrupt blood flow during the intervention. We aim to introduce a new technique that allows a sutureless, non-occlusive revascularization. A 3-step technique was developed using rabbit's aorta to simulate a side-to-side anastomosis model.

Polarimetric imaging in backscattering for the structural characterization of strongly scattering birefringent fibrous media.

Interpreting the polarimetric data from fiber-like macromolecules constitutive of tissue can be difficult due to strong scattering. In this study, we probed the superficial layers of fibrous tissue models (membranes consisting of nanofibers) displaying varying degrees of alignment. To better understand the manifestation of membranes' degree of alignment in polarimetry, we analyzed the spatial variations of the backscattered light's Stokes vectors as a function of the orientation of the probing beam's linear polarization.

Improved forward model for quantitative pulse-echo speed-of-sound imaging.

Computed ultrasound tomography in echo mode (CUTE) allows determining the spatial distribution of speed-of-sound (SoS) inside tissue using handheld pulse-echo ultrasound (US). This technique is based on measuring the changing phase of beamformed echoes obtained under varying transmit (Tx) and/or receive (Rx) steering angles. The SoS is reconstructed by inverting a forward model describing how the spatial distribution of SoS is related to the spatial distribution of the echo phase shift.

Reliability assessment for blood oxygen saturation levels measured with optoacoustic imaging.

Significance: Quantitative optoacoustic (OA) imaging has the potential to provide blood oxygen saturation (SO2) estimates due to the proportionality between the measured signal and the blood's absorption coefficient. However, due to the wavelength-dependent attenuation of light in tissue, a spectral correction of the OA signals is required, and a prime challenge is the validation of both the optical characterization of the tissue and the SO2.

Aim: We propose to assess the reliability of SO2 levels retrieved from spectral fitting by measuring the similarity of OA spectra to the fitted blood absorption spectra.

Grafting of calcium chelating functionalities onto PLA monofilament fiber surfaces.

Polymer surface grafting is widely used in the field of bone regeneration to increase calcium phosphate (CaP) adhesion, with the intent of improving mechanical properties of CaP-polymer composite cements. Reinforcement can be achieved using multiple combined functional groups and/or complex surface geometries that, however, concurrently influence multiple effects such as wetting, roughness, and interfacial strengthening. This study focused on the influence of a chelating group, namely aspartic acid, on the adsorption of divalent ions such as Ba or Ca onto poly-l-lactic acid (PLA) films.

Quantitative comparison of frequency-domain and delay-and-sum optoacoustic image reconstruction including the effect of coherence factor weighting.

Image reconstruction in optoacoustic imaging is often based on a delay-and-sum (DAS) or a frequency domain (FD) algorithm. In this study, we performed a comprehensive comparison of these two algorithms together with coherence factor (CF) weighting using phantom and in-vivo mouse data obtained with optoacoustic microscopy. For this purpose we developed an FD based definition of the CF.