Reflection mode photoacoustic measurement of speed of sound

We present a method to determine the speed of sound in tissue using a double-ring photoacoustic sensor working in reflection mode. This method uses the cross-correlation between the laser-induced ultrasound waves detected by two concentric ring shaped sensors, while a priori information about the depth-position of the photoacoustic source is not required. We demonstrate the concept by estimating the speed of sound in water as a function of temperature. Comparison of the estimated speed with values reported in literature shows an average systematic error of 0.1% and a standard deviation of 0.1%. Furthermore, we demonstrate that the method can be applied to layered media. The method has application in the correction of photoacoustic and ultrasound images afflicted by local speed variations in tissue. Additionally, the concept shows promise in monitoring temperature changes which are reflected in speed of sound changes in tissue.\ud \u

Feasibility of noncontact piezoelectric detection of photoacoustic signals in tissue-mimicking phantoms

The feasibility of air-coupled ultrasound transducers to detect laser-induced ultrasound from artificial blood vessels embedded in an optically scattering phantom is demonstrated. These air-coupled transducers allow new applications in biomedical photoacoustic imaging where contact with tissue is not preferred. One promising application of such transducers is the addition of photoacoustic imaging to the regular x-ray mammographic screening procedure

The preclinical pharmacology of the high affinity anti-IL-6R Nanobody (R) ALX-0061 supports its clinical development in rheumatoid arthritis

Introduction: The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody (R) with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology. Methods: ALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species, and in a collagen-induced arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control. Results: ALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after a single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkeys, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the study duration. Conclusions: ALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA

Real-time in vivo photoacoustic and ultrasound imaging

A real-time photoacoustic imaging system is designed and built. This system is based on a commercially available ultrasound imaging system. It can achieve a frame rate of 8 frames/sec. Vasculature in the hand of a human volunteer is imaged, and the resulting photoacoustic image is combined with the ultrasound image. The real-time photo acoustic imaging system with a hybrid ultrasound probe is demonstrated by imaging the branching of subcutaneous blood vessels in the hand. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3005421

Real-time in vivo photoacoustic and ultrasound imaging\ud

A real-time photoacoustic imaging system is designed and built. This system is based on a commercially available ultrasound imaging system. It can achieve a frame rate of 8 frames/sec. Vasculature in the hand of a human volunteer is imaged, and the resulting photoacoustic image is combined with the ultrasound image. The real-time photo acoustic imaging system with a hybrid ultrasound probe is demonstrated by imaging the branching of subcutaneous blood vessels in the han