Abstract
.Significance: Three-dimensional (3D) vascular and metabolic imaging (VMI) of whole organs in rodents provides critical and important (patho)physiological information in studying animal models of vascular network.Aim: Autofluorescence metabolic imaging has been used to evaluate mitochondrial metabolites such as nicotinamide adenine dinucleotide (NADH) and flavine adenine dinucleotide (FAD). Leveraging these autofluorescence images of whole organs of rodents, we have developed a 3D vascular segmentation technique to delineate the anatomy of the vasculature as well as mitochondrial metabolic distribution.Approach: By measuring fluorescence from naturally occurring mitochondrial metabolites combined with light-absorbing properties of hemoglobin, we detected the 3D structure of the vascular tree of rodent lungs, kidneys, hearts, and livers using VMI. For lung VMI, an exogenous fluorescent dye was injected into the trachea for inflation and to separate the airways, confirming no overlap between the segmented vessels and airways.Results: The kidney vasculature from genetically engineered rats expressing endothelial-specific red fluorescent protein TdTomato confirmed a significant overlap with VMI. This approach abided by the “minimum work” hypothesis of the vascular network fitting to Murray’s law. Finally, the vascular segmentation approach confirmed the vascular regression in rats, induced by ionizing radiation.Conclusions: Simultaneous vascular and metabolic information extracted from the VMI provides quantitative diagnostic markers without the confounding effects of vascular stains, fillers, or contrast agents.
Highlights
Damaged vasculature and the resulting impaired blood circulation in organs can cause pathological injuries, such as organ failure and stroke.[1]
Using histology for vascular imaging of small animals requires the development of molecular tools such as specific antibodies[12,13] or the development of transgenic mice expressing endothelial-specific markers.[14]
Positron emission tomography (PET) can be used to provide specific molecular information,[22] while a hybrid imaging technology, such as positron emission tomography (PET)-CT,[23] acquires anatomical and molecular information but in turn comes with increased cost, acquisition time, and complexity
Summary
Damaged vasculature and the resulting impaired blood circulation in organs can cause pathological injuries, such as organ failure and stroke.[1] vascular imaging plays a pivotal role in diagnosis, follow-up of disease progression, and assessment of treatment efficacy.[2] Assessment of vascular structure in rodent models is key to quantitate organ vasculature.[3,4] This quantitation could be beneficial in analyzing pathological conditions, such as hypertension,[5] diabetes,[6] and retinopathy[7] as well as changes induced by environmental or chemical agents such as radiation[8] or drugs.[9] Vascular imaging is important to study therapeutic angiogenesis.[10]. Labeling with a contrast agent or filler is required for most of these vascular imaging technologies,[19] each having its limitations. Positron emission tomography (PET) can be used to provide specific molecular information,[22] while a hybrid imaging technology, such as PET-CT,[23] acquires anatomical and molecular information but in turn comes with increased cost, acquisition time, and complexity
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