A novel pilot animal model for the surgical prevention of lymphedema: the power of optical imaging.

BACKGROUND: Breast cancer-related lymphedema affects more than 400,000 survivors in the United States. In 2009, lymphatic microsurgical preventive healing approach (LYMPHA) was first described as a surgical technique to prevent lymphedema by bypassing divided arm lymphatics into adjacent veins at the time of an axillary lymph node dissection. We describe the first animal model of LYMPHA. METHODS: In Yorkshire pigs, each distal hind limb lymphatic system was cannulated and injected with a different fluorophore (human serum albumin-conjugated indocyanine green or Evans Blue). Fluorescence-assisted resection and exploration imaging system was used to map the respective lymphangiosomes to the groin. Baseline lymphatic clearance of each hind limb lymphangiosome was obtained by measuring the fluorescence of each dye from centrally obtained blood samples. A lymphadenectomy versus lymphadenectomy with LYMPHA was then performed. The injections were then repeated to obtain clearance rates that were compared against baseline values. RESULTS: Human serum albumin-conjugated indocyanine green and Evans Blue allowed for precise lymphatic mapping of each respective hind limb using fluorescence-assisted resection and exploration imaging. Lymphatic clearance from the distal hind limb dropped 68% when comparing baseline clearance versus after a groin lymphadenectomy. In comparison, lymphatic clearance dropped only 21% when comparing baseline clearance versus a lymphadenectomy with LYMPHA. CONCLUSIONS: We describe the first animal model for LYMPHA, which will enable future studies to further evaluate the efficacy and potential limitations of this technique. Of equal importance, we demonstrate the power of optical imaging to provide real-time lymphatic clearance rates for each hind limb.

Decomposition of the factors that govern binding site preference in a multiple rotaxane.

A particularly interesting class of multiple rotaxanes consists of complexes where one long shaft threads two rings. If the shaft contains three or more potential binding sites for the rings, multiple co-conformations are possible. Such a complex is a molecular topological analogue to an abacus. Here we address the question, how does strength of ring binding to the shaft vary with respect to position on the shaft? Previous studies have found that a shaft with three binding sites exhibits strongest ring binding at the center site. Here a five-binding-site shaft is studied. We employ a novel method to partition the total energy of the system into contributions from intercomponent binding and intracomponent distortion. The method uses the output of quantum mechanical electronic structure calculations to determine fitting parameters in a set of coupled equations. The solution of the equations yields the energy partitioning and reveals the influence of long-range intercomponent interactions.

Structured illumination Mueller matrix imaging.

We perform Mueller matrix imaging (MMI) of diffusely scattering phantoms under sinusoidal irradiance of varying spatial frequency. Quantitative polarimetric sensing via MMI completely characterizes a sample's polarimetric properties, while structured illumination (SI) allows for the control of photon path length. Intralipid phantoms were measured with varying absorption and with varying depth to demonstrate photon path length control for Mueller matrix elements. We observe unpolarized intensity, linear polarization, and circular polarization to depend upon spatial frequency differently. Finally, we measured an ex vivo chicken skin sample over a bright and dark substrate to further demonstrate the sensitivity of SI-MMI to depth.

Technological Advances in Lymphatic Surgery: Bringing to Light the Invisible.

Lymphatic surgery has become an integral and flourishing component of the field of plastic surgery. The diversity of ongoing technological innovations in perioperative imaging, including intraoperative dyes and cameras, allows plastic surgeons to work at the supermicrosurgical level. This study aims to highlight innovations that have shaped and will continue to revolutionize the perioperative management of the lymphatic surgery patient in the future. As additional advances emerge, we need a systematic and objective way to evaluate the efficacy and clinical integration readiness of such technologies. Undoubtedly, these technologies will help lymphatic surgery trend toward increasing objectivity, which will be critical for continued evolution and advancement.

Review of structured light in diffuse optical imaging.

Diffuse optical imaging probes deep living tissue enabling structural, functional, metabolic, and molecular imaging. Recently, due to the availability of spatial light modulators, wide-field quantitative diffuse optical techniques have been implemented, which benefit greatly from structured light methodologies. Such implementations facilitate the quantification and characterization of depth-resolved optical and physiological properties of thick and deep tissue at fast acquisition speeds. We summarize the current state of work and applications in the three main techniques leveraging structured light: spatial frequency-domain imaging, optical tomography, and single-pixel imaging. The theory, measurement, and analysis of spatial frequency-domain imaging are described. Then, advanced theories, processing, and imaging systems are summarized. Preclinical and clinical applications on physiological measurements for guidance and diagnosis are summarized. General theory and method development of tomographic approaches as well as applications including fluorescence molecular tomography are introduced. Lastly, recent developments of single-pixel imaging methodologies and applications are reviewed.

Real-time endoscopic optical properties imaging.

With almost 50% of all surgeries in the U.S. being performed as minimally invasive procedures, there is a need to develop quantitative endoscopic imaging techniques to aid surgical guidance. Recent developments in widefield optical imaging make endoscopic implementations of real-time measurement possible. In this work, we introduce a proof-of-concept endoscopic implementation of a functional widefield imaging technique called 3D single snapshot of optical properties (3D-SSOP) that provides quantitative maps of absorption and reduced scattering optical properties as well as surface topography with simple instrumentation added to a commercial endoscope. The system's precision and accuracy is validated using tissue-mimicking phantoms, showing a max error of 0.004 mm-1, 0.05 mm-1, and 1.1 mm for absorption, reduced scattering, and sample topography, respectively. This study further demonstrates video acquisition of a moving phantom and an in vivo sample with a framerate of approximately 11 frames per second.

Application of semiempirical electronic structure theory to compute the force generated by a single surface-mounted switchable rotaxane.

Herein we report a study of the switchable [3]rotaxane reported by Huang et al. (Appl Phys Lett 85(22):5391-5393, 1) that can be mounted to a surface to form a nanomechanical, linear, molecular motor. We demonstrate the application of semiempirical electronic structure theory to predict the average and instantaneous force generated by redox-induced ring shuttling. Detailed analysis of the geometric and electronic structure of the system reveals technical considerations essential to success of the approach. The force is found to be in the 100-200 pN range, consistent with published experimental estimates. Graphical Abstract A single surface-mounted switchable rotaxane.

qF-SSOP: real-time optical property corrected fluorescence imaging.

Fluorescence imaging is well suited to provide image guidance during resections in oncologic and vascular surgery. However, the distorting effects of tissue optical properties on the emitted fluorescence are poorly compensated for on even the most advanced fluorescence image guidance systems, leading to subjective and inaccurate estimates of tissue fluorophore concentrations. Here we present a novel fluorescence imaging technique that performs real-time (i.e., video rate) optical property corrected fluorescence imaging. We perform full field of view simultaneous imaging of tissue optical properties using Single Snapshot of Optical Properties (SSOP) and fluorescence detection. The estimated optical properties are used to correct the emitted fluorescence with a quantitative fluorescence model to provide quantitative fluorescence-Single Snapshot of Optical Properties (qF-SSOP) images with less than 5% error. The technique is rigorous, fast, and quantitative, enabling ease of integration into the surgical workflow with the potential to improve molecular guidance intraoperatively.

Real-time, profile-corrected single snapshot imaging of optical properties.

A novel acquisition and processing method that enables real-time, single snapshot of optical properties (SSOP) and 3-dimensional (3D) profile measurements in the spatial frequency domain is described. This method makes use of a dual sinusoidal wave projection pattern permitting to extract the DC and AC components in the frequency domain to recover optical properties as well as the phase for measuring the 3D profile. In this method, the 3D profile is used to correct for the effect of sample's height and angle and directly obtain profile-corrected absorption and reduced scattering maps from a single acquired image. In this manuscript, the 3D-SSOP method is described and validated on tissue-mimicking phantoms as well as in vivo, in comparison with the standard profile-corrected SFDI (3D-SFDI) method. On average, in comparison with 3D-SFDI method, the 3D-SSOP method allows to recover the profile within 1.2mm and profile-corrected optical properties within 12% for absorption and 6% for reduced scattering over a large field-of-view and in real-time.