We present photoacoustic computed tomography through an ergodic relay (PACTER), a method for single-shot 3D imaging of hemodynamics using a single-element detector. Our approach allows for ultrafast volumetric imaging at kilohertz rates without the need for numerous detector elements. We demonstrate PACTER in both human and small animal subjects, emphasizing its potential utility in early detection and monitoring of peripheral vascular diseases. Our single-element detector design aims to offer a more convenient and potentially affordable option, while the concept could also be relevant to other imaging technologies, contributing to various applications in medical imaging.
SignificanceOver 100 monoclonal antibodies have been approved by the U.S. Food and Drug Administration (FDA) for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, particularly the effect of antibody, formulation, and tissue at the injection site. A deeper understanding of antibody behavior at the injection site, especially on blood oxygenation through imaging, will help design improved versions of the therapeutics for a wide range of diseases.AimThe aim of this research is to understand the dynamics of monoclonal antibodies at the injection site as well as how the antibody itself affects the functional characteristics of the injection site [e.g., blood oxygen saturation (sO2)].ApproachWe employed triple-wavelength equipped functional photoacoustic imaging to study the dynamics of dye-labeled and unlabeled monoclonal antibodies at the site of injection in a mouse ear. We injected a near-infrared dye-labeled (and unlabeled) human IgG4 isotype control antibody into the subcutaneous space in mouse ears to analyze the injection site dynamics and quantify molecular movement, as well as its effect on local hemodynamics.ResultsWe performed pharmacokinetic studies of the antibody in different regions of the mouse body to show that dye labeling does not alter the pharmacokinetic characteristics of the antibody and that mouse ear is a viable model for these initial studies. We explored the movement of the antibody in the interstitial space to show that the bolus area grows by ∼300 % over 24 h. We discovered that injection of the antibody transiently reduces the local sO2 levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction.ConclusionsThis finding on local oxygen saturation opens a new avenue of study on the functional effects of monoclonal antibody injections. We also show the suitability of the mouse ear model to study antibody dynamics through high-resolution imaging techniques. We quantified the movement of antibodies at the injection site caused by the interstitial fluid, which could be helpful for designing antibodies with tailored absorption speeds in the future.
In vivo imaging of blood flow is the key for mapping circulatory system function. While photoacoustic computed tomography (PACT) is well-established for imaging deep blood vessels, its feasibility for measuring blood flow beyond the optical diffusion limit (one millimeter) has not been demonstrated. Herein, we report, to our knowledge, the first use of PACT to image deep blood flow in humans. We achieved a penetration depth greater than five millimeters and obtained both the speed and direction as a vector flow map. This work establishes PACT as a powerful tool to study the rich contrast of blood and its hemodynamics.
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