Biology subjects

de la Zerda, A.

Publications and source records attributed to de la Zerda, A..

4 recordsLinked to original sources

bioRxiv2018

Gold Nanoprisms as Optical Coherence Tomography Contrast Agents in the Second Near Infrared Window for Enhanced Angiography in Live Animals

Optical coherence tomography angiography (OCTA) is an important tool for investigating vascular networks and microcirculation in living tissue. Traditional OCTA detects blood vessels via intravascular dynamic scattering signals derived from the movements of red blood cells (RBCs). However, the low hematocrit and long latency between RBCs in capillaries makes these OCTA signals discontinuous, leading to incomplete mapping of the vascular networks. OCTA imaging of microvascular circulation is particularly challenging in tumors due to the abnormally slow blood flow in angiogenic tumor vessels and strong attenuation of light by tumor tissue. Here we demonstrate in vivo that gold nanoprisms (GNPRs) can be used as OCT contrast agents working in the second near infrared window, significantly enhancing the dynamic scattering signals in microvessels and improving the sensitivity of OCTA in skin tissue and melanoma tumors in live mice. This is the first demonstration that nanoparticle-based OCT contrast agent work in vivo in the second near infrared window, which allows deeper imaging depth by OCT. With GNPRs as contrast agents, the post-injection OCT angiograms showed 41% and 59% more microvasculature than pre-injection angiograms in healthy mouse skin and melanoma tumors, respectively. By enabling better characterization of microvascular circulation in vivo, GNPR-enhanced OCTA could lead to better understanding of vascular functions during pathological conditions, more accurate measurements of therapeutic response, and improved patient prognoses.

bioengineering↗

bioRxiv2018

High-resolution wide-field human brain tumor margin detection and in vivo murine neuroimaging

Current in vivo neuroimaging techniques provide limited field of view or spatial resolution and often require exogenous contrast. These limitations prohibit detailed structural imaging across wide fields of view and hinder intraoperative tumor margin detection. Here we present a novel neuroimaging technique, speckle-modulating optical coherence tomography (SM-OCT), which allows us to image the brains of live mice and ex vivo human samples with unprecedented resolution and wide field of view using only endogenous contrast. The increased effective resolution provided by speckle elimination reveals white matter fascicles and cortical layer architecture in the brains of live mice. To our knowledge, the data reported herein represents the highest resolution imaging of murine white matter structure achieved in vivo across a wide field of view of several millimeters. When applied to an orthotopic murine glioblastoma xenograft model, SM-OCT readily identifies brain tumor margins with near single-cell resolution. SM-OCT of ex vivo human temporal lobe tissue reveals fine structures including cortical layers and myelinated axons. Finally, when applied to an ex vivo sample of a low-grade glioma resection margin, SM-OCT is able to resolve the brain tumor margin. Based on these findings, SM-OCT represents a novel approach for intraoperative tumor margin detection and in vivo neuroimaging.

bioengineering↗

bioRxiv2017

Upper Limit for Angular Compounding Speckle Reduction

Previous studies of angular compounding for speckle reduction in optical coherence tomography may not have fully accounted for optical aberrations, which produce unintended spatial averaging and concomitant loss of spatial resolution. We accounted for such aberrations by aligning our system and measuring distortions in the images, and found that speckle reduction by angular compounding was limited. Our theoretical analysis using Monte Carlo simulations indicates that \"pure\" angular compounding over 13{degrees} (our full numerical aperture) can improve the signal-to-noise ratio by no more than a factor of 1.5, significantly lower than values reported in literature. Analysis suggests that illuminating only part of the lens to further reduce speckle also involves a trade-off with resolution roughly equivalent to spatial averaging. We conclude that angular compounding provides substantially less benefit than previously expected.

bioengineering↗

bioRxiv2017

Wide-field dynamic monitoring of immune cell trafficking in murine models of glioblastoma

Leukocyte populations, especially tumor-associated macrophages (TAMs), are capable of mediating both anti- and pro-tumor processes and play significant roles in the tumor microenvironment. Moreover, TAMs have been shown to exert substantial influence on the efficacy of various cancer immunotherapy treatment strategies. Laboratory investigation into the behavior of TAMs has been limited by a lack of methods capable of resolving the in vivo distribution and dynamics of this cell population across wide fields of view. Recent studies have employed magnetic resonance imaging and intravital microscopy in conjunction with nanoparticle labeling methods to detect TAMs and observe their responses to therapeutic agents. Here we describe a novel method to enable high-resolution, wide-field, longitudinal imaging of leukocytes based on contrast-enhanced Speckle-Modulating Optical Coherence Tomography (SM-OCT), which substantially reduces imaging noise. We were able to specifically label TAMs and activated microglia in vivo with large gold nanorod contrast agents (LGNRs) in an orthotopic murine glioblastoma model. After labeling, we demonstrated near real-time tracking of leukocyte migration and distribution within the tumors. The intrinsic resolution, imaging depth, and sensitivity of this method may facilitate detailed studies of the fundamental behaviors of TAMs in vivo, including their intratumoral distribution heterogeneity and the roles they play in modulating cancer proliferation. In future studies, the method described herein may also provide the necessary means to characterize TAM responses to immunotherapeutic regimens in a range of solid tumors.

bioengineering↗