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In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

ABSTRACT: Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields (QY), relatively long emission wavelengths, and high signal-to-noise ratios (SNRs) to fulfill the requirements for 3D brain imaging in vivo. With assistance from density-function theory (DFT) computation, we designed ADLumin-Xs by locking up the rotation of the double-bond via fusing the furan ring to the phenyl ring. Our results showed that ADLumin-5 had a high quantum yield of chemiluminescence and could bind to amyloid beta (Aβ). Remarkably, ADLumin-5's radiance intensity in brain areas could reach 4×10⁷ photon/s/cm²/sr, which is probably 100-fold higher than most chemiluminescence probes for in vivo imaging. Because of its strong emission, we demonstrated that ADLumin-5 could be used for in vivo 3D brain imaging in transgenic mouse models of Alzheimer's disease (AD).

SUBMITTER: Zhang J

PROVIDER: S-EPMC10350002 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

Zhang Jing J Wickizer Carly C Ding Weihua W Van Richard R Yang Liuyue L Zhu Biyue B Yang Jun J Zhang Can C Shen Shiqian S Shao Yihan Y Ran Chongzhao C

bioRxiv : the preprint server for biology 20230703

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields (QY), relatively long emission wavelengths, and high signal-to-noise ratios (SNRs) to fulfill the requirements ...[more]

PMID: 37461700

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Project description:Rationale: Continued reliance on preclinical animal models and traditional human cell culture experiments conducted on supraphysiologically stiff surfaces in two dimensions often limits the translation of cellular and molecular mechanistic findings into effective therapies for patients suffering from chronic obstructive pulmonary disease (COPD). COPD ranks as the fourth highest cause of mortality in the United States, and thus it is imperative to improve ex vivo models of this devastating disease. One emerging novel model of study involves using precision-cut lung slices as three-dimensional lung tissue culture (3D-LTC) platforms. Although this model retains the complex pulmonary architecture required for more precise ex vivo modeling, it is limited by short-term viability (?5–7 d). Objectives: We hypothesized that this decrease in viability is related to slices losing the extracellular matrix adhesion foundation critical for normal cellular functioning and that encapsulation of slices in custom hydrogel microenvironments would improve maintenance of a stable phenotype for longer-term investigational studies. Methods: The 3D-LTC slices tested here were created according to standard protocols from healthy mouse lungs and from the lungs of a patient with COPD. We synthesized poly(ethylene glycol)–based polymers to create custom hydrogels for encapsulation of 3D-LTCs with mechanical properties that match each type of lung tissue. The Young’s modulus (E) or stiffness of hydrogels was measured with a parallel-plate rheometer. Lung slices were analyzed for viability with a colorimetric assay that measures cellular metabolism (WST-1; Millipore Sigma) and by staining for cell membrane integrity (Invitrogen LIVE/DEAD viability kit; Thermo Fisher Scientific). All fluorescently labeled samples were imaged by spinning disk confocal microscopy, and cell viability at all time points was analyzed with ImageJ software. Results: The average percent viability of cells within hybrid 3D-LTCs was consistently higher than control 3D-LTCs on Day 1 (35% increase; P?<?0.001) and Day 7 (55% increase; P?<?0.001) according to LIVE/DEAD staining results. The WST-1 assay further showed no significant difference in viability between the two systems up to Day 18 in culture. Conclusions: We have demonstrated that it is possible to create customized hydrogel platforms that replicate the stiffness of healthy mouse and human COPD lung tissues. Precision cut lung slices embedded in these materials maintain higher levels of viability compared with controls in culture. Further optimization of this technology platform is ongoing and will facilitate the development of more organotypic ex vivo models of chronic pulmonary disease.

Dataset Information

In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

Publications

In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

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