Publications by authors named "Daniel A Gil"

Patient-derived cancer organoids (PCOs) are organotypic models that reflect drug response, thus PCOs are an accessible model for cancer drug screening in a clinically relevant timeframe. However, current methods to assess the response of PCOs are limited. Here, a custom swept-source optical coherence tomography (OCT) system was used to rapidly evaluate volumetric growth and drug response in PCOs.

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Purpose: To assess the performance of two spectral-domain optical coherence tomography-angiography systems in a natural model of hypoperfusion: the hibernating thirteen-lined ground squirrel (13-LGS).

Methods: Using a high-speed (130 kHz) OCT-A system (HS-OCT-A) and a commercial OCT (36 kHz; Bioptigen Envisu; BE-OCT-A), we imaged the 13-LGS retina throughout its hibernation cycle. Custom software was used to extract the superior, middle, and deep capillary plexus (SCP, MCP, and DCP, respectively).

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Significance: Accessible tools are needed for rapid, non-destructive imaging of patient-derived cancer organoid (PCO) treatment response to accelerate drug discovery and streamline treatment planning for individual patients.

Aim: To segment and track individual PCOs with wide-field one-photon redox imaging to extract morphological and metabolic variables of treatment response.

Approach: Redox imaging of the endogenous fluorophores, nicotinamide dinucleotide (NADH), nicotinamide dinucleotide phosphate (NADPH), and flavin adenine dinucleotide (FAD), was used to monitor the metabolic state and morphology of PCOs.

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Endothelial cells (EC) in vivo are continuously exposed to a mechanical microenvironment from blood flow, and fluidic shear stress plays an important role in EC behavior. New approaches to generate physiologically and pathologically relevant pulsatile flows are needed to understand EC behavior under different shear stress regimes. Here, we demonstrate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows from human pluripotent stem cell-derived cardiac spheroids (CS) via quantitative imaging-based signal transduction.

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High-throughput drug screening of patient-derived organoids offers an attractive platform to determine cancer treatment efficacy. Here, selective plane illumination microscopy (SPIM) was used to determine treatment response in organoids with endogenous fluorescence from the metabolic coenzymes NAD(P)H and FAD. Rapid 3-D autofluorescence imaging of colorectal cancer organoids was achieved.

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Optical coherence tomography (OCT) is an emerging technology for in vivo airway and lung imaging. However, OCT lacks sensitivity to the metabolic changes caused by inflammation, which drives chronic respiratory diseases such as asthma and chronic obstructive pulmonary disorder. Redox imaging (RI) is a label-free technique that uses the autofluorescence of the metabolic coenzymes NAD(P)H and flavin adenine dinucleotide (FAD) to probe cellular metabolism and could provide complimentary information to OCT for airway and lung imaging.

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Article Synopsis
  • Vascularization is crucial for overcoming diffusion limits in creating complex engineered tissues and organoids, which can be achieved through self-assembly of vascular networks using stem cell-derived endothelial cells and pericytes in hydrogels.* -
  • Autofluorescence multiphoton microscopy (aMPM) is utilized as a label-free imaging method to quantitatively assess the morphology of these in vitro vascular networks without needing traditional fixation or labeling.* -
  • Findings showed that bioreactors using recirculating or continuous fluid flow improve vascular network formation by reducing anisotropy and increasing branch points compared to static conditions, supporting the effectiveness of aMPM for optimizing tissue growth conditions.*
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Microwave ablation is a minimally invasive image guided thermal therapy for cancer that can be adapted to endoscope use in the gastrointestinal (GI) tract. Microwave ablation in the GI tract requires precise control over the ablation zone that could be guided by high resolution imaging with quantitative contrast. Optical coherence tomography (OCT) provides ideal imaging resolution and allows for the quantification of tissue scattering properties to characterize ablated tissue.

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Radiofrequency ablation (RFA) is a widely used treatment for atrial fibrillation, the most common cardiac arrhythmia. Here, we explore autofluorescence hyperspectral imaging (aHSI) as a method to visualize RFA lesions and interlesional gaps in the highly collagenous left atrium. RFA lesions made on the endocardial surface of freshly excised porcine left atrial tissue were illuminated by UV light (365 nm), and hyperspectral datacubes were acquired over the visible range (420-720 nm).

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Background: Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures.

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