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1. Mapping electrical properties heterogeneity of tumor using boundary informed electrical properties tomography (BIEPT) at 7T

   https://doi.org/10.1002/mrm.27414  

   Wang, Yicun ; Shao, Qi ; Van de Moortele, Pierre‐Francois ; Racila, Emilian ; Liu, Jiaen ; Bischof, John ; He, Bin ( September 2018 , Magnetic Resonance in Medicine)

   To develop and evaluate a boundary informed electrical properties tomography (BIEPT) technique for high‐resolution imaging of tumor electrical properties (EPs) heterogeneity on a rodent tumor xenograft model.

   Tumor EP distributions were inferred from a reference area external to the tumor, as well as internal EP spatial variations derived from a plurality of relative transmit B₁measurements at 7T. Edge sparsity constraint was enforced to enhance numerical stability. Phantom experiments were performed to determine the imaging accuracy and sensitivity for structures of various EP values, as well as geometrical sizes down to 1.5 mm. Numerical simulation of a realistic rodent model was used to quantify the algorithm performance in the presence of noise. Eleven athymic rats with human breast cancer xenograft were imaged in vivo, and representative pathological samples were acquired for comparison.

   Reconstructed EPs of the phantoms correspond well to the ground truth acquired from dielectric probe measurements, with the smallest structure reliably detectable being 3 mm. EPs heterogeneity inside a tumor is successfully retrieved in both simulated and experimental cases. In vivo tumor imaging results demonstrate similar local features and spatial patterns to anatomical MRI and pathological slides. The imaged conductivity of necrotic tissue is higher than that of viable tissues, which agrees with our expectation.

   BIEPT enables robust detection of tumor EPs heterogeneity with high accuracy and sensitivity to small structures. The retrieved quantitative EPs reflect tumor pathological features (e.g., necrosis). These results provide strong rationale to further expand BIEPT studies toward pathological conditions where EPs may yield valuable, non‐invasive biomarkers.

    

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2. Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

   https://doi.org/10.1038/s41467-018-06730-z  

   Dogra, Prashant ; Adolphi, Natalie L. ; Wang, Zhihui ; Lin, Yu-Shen ; Butler, Kimberly S. ; Durfee, Paul N. ; Croissant, Jonas G. ; Noureddine, Achraf ; Coker, Eric N. ; Bearer, Elaine L. ; et al ( October 2018 , Nature Communications)

   The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.

    

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3. High-Performance Red/Near-IR Carbon Dots as Fluorescence Probes for Tumor Imaging In Vivo

   https://doi.org/10.1002/slct.201800814  

   Yang, Sheng-Tao ; Liu, Jia-Hui ; Wang, Ping ; Yang, Shengnan ; Ge, Lin ; Yan, Sijia ; Sun, Ya-Ping ( June 2018 , ChemistrySelect)
4. Towards in-vivo label-free detection of brain tumor margins with epi-illumination tomographic quantitative phase imaging

   https://doi.org/10.1364/BOE.416731  

   Costa, Paloma Casteleiro ; Guang, Zhe ; Ledwig, Patrick ; Zhang, Zhaobin ; Neill, Stewart ; Olson, Jeffrey J. ; Robles, Francisco E. ( February 2021 , Biomedical Optics Express)

   Brain tumor surgery involves a delicate balance between maximizing the extent of tumor resection while minimizing damage to healthy brain tissue that is vital for neurological function. However, differentiating between tumor, particularly infiltrative disease, and healthy brain in-vivo remains a significant clinical challenge. Here we demonstrate that quantitative oblique back illumination microscopy (qOBM)—a novel label-free optical imaging technique that achieves tomographic quantitative phase imaging in thick scattering samples—clearly differentiates between healthy brain tissue and tumor, including infiltrative disease. Data from a bulk and infiltrative brain tumor animal model show that qOBM enables quantitative phase imaging of thick fresh brain tissues with remarkable cellular and subcellular detail that closely resembles histopathology using hematoxylin and eosin (H&E) stained fixed tissue sections, the gold standard for cancer detection. Quantitative biophysical features are also extracted from qOBM which yield robust surrogate biomarkers of disease that enable (1) automated tumor and margin detection with high sensitivity and specificity and (2) facile visualization of tumor regions. Finally, we develop a low-cost, flexible, fiber-based handheld qOBM device which brings this technology one step closer to in-vivo clinical use. This work has significant implications for guiding neurosurgery by paving the way for a tool that delivers real-time, label-free, in-vivo brain tumor margin detection.

    

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5. Self-assembled peptide-dye nanostructures for in vivo tumor imaging and photodynamic toxicity

   https://doi.org/10.1038/s44303-024-00008-4  

   Borum, Raina M. ; Retout, Maurice ; Creyer, Matthew N. ; Chang, Yu-Ci ; Gregorio, Karlo ; Jokerst, Jesse V. ( March 2024 , npj Imaging)

   We report noncovalent assemblies of iRGD peptides and methylene blue dyes via electrostatic and hydrophobic stacking. These resulting nanomaterials could bind to cancer cells, image them with photoacoustic signal, and then treat them via photodynamic therapy. We first assessed the optical properties and physical properties of the materials. We then evaluated their utility for live cell targeting, in vivo imaging, and in vivo photodynamic toxicity. We tuned the performance of iRGD by adding aspartic acid (DD) or tryptophan doublets (WW) to the peptide to promote electrostatic or hydrophobic stacking with methylene blue, respectively. The iRGD-DD led to 150-nm branched nanoparticles, but iRGD-WW produced 200-nm nano spheres. The branched particles had an absorbance peak that was redshifted to 720 nm suitable for photoacoustic signal. The nanospheres had a peak at 680 nm similar to monomeric methylene blue. Upon continuous irradiation, the nanospheres and branched nanoparticles led to a 116.62% and 94.82% increase in reactive oxygen species in SKOV-3 cells relative to free methylene blue at isomolar concentrations suggesting photodynamic toxicity. Targeted uptake was validated via competitive inhibition. Finally, we used in vivo bioluminescent signal to monitor tumor burden and the effect of for photodynamic therapy: The nanospheres had little impact versus controls (p = 0.089), but the branched nanoparticles slowed SKOV-3 tumor burden by 75.9% (p < 0.05).

    

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