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Magnetic and contrast properties of labeled platelets for magnetomotive optical coherence tomography.

ABSTRACT: This article introduces a new functional imaging paradigm that uses optical coherence tomography (OCT) to detect rehydrated, lyophilized platelets (RL platelets) that are in the preclinical trial stage and contain superparamagnetic iron oxides (SPIOs) approved by the U.S. Food and Drug Administration. Platelets are highly functional blood cells that detect and adhere to sites of vascular endothelial damage by forming primary hemostatic plugs. By applying magnetic gradient forces, induced nanoscale displacements (magnetomotion) of the SPIO-RL platelets are detected as optical phase shifts in OCT. In this article, we characterize the iron content and magnetic properties of SPIO-RL platelets, construct a model to predict their magnetomotion in a tissue medium, and demonstrate OCT imaging in tissue phantoms and ex vivo pig arteries. Tissue phantoms containing SPIO-RL platelets exhibited >3 dB contrast/noise ratio at ?1.5 × 10(9) platelets/cm(3). OCT imaging was performed on ex vivo porcine arteries after infusion of SPIO-RL platelets, and specific contrast was obtained on an artery that was surface-damaged (P < 10(-6)). This may enable new technologies for in vivo monitoring of the adherence of SPIO-RL platelets to sites of bleeding and vascular damage, which is broadly applicable for assessing trauma and cardiovascular diseases.

SUBMITTER: Oldenburg AL

PROVIDER: S-EPMC3042564 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Magnetic and contrast properties of labeled platelets for magnetomotive optical coherence tomography.

Oldenburg Amy L AL Gallippi Caterina M CM Tsui Frank F Nichols Timothy C TC Beicker Kellie N KN Chhetri Raghav K RK Spivak Dmitry D Richardson Aaron A Fischer Thomas H TH

Biophysical journal 20101001 7

This article introduces a new functional imaging paradigm that uses optical coherence tomography (OCT) to detect rehydrated, lyophilized platelets (RL platelets) that are in the preclinical trial stage and contain superparamagnetic iron oxides (SPIOs) approved by the U.S. Food and Drug Administration. Platelets are highly functional blood cells that detect and adhere to sites of vascular endothelial damage by forming primary hemostatic plugs. By applying magnetic gradient forces, induced nanosca ...[more]

PMID: 20923673

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Project description:Rationale: Magnetic nanoparticle hyperthermia (MH) therapy is capable of thermally damaging tumor cells, yet a biomechanically-sensitive monitoring method for the applied thermal dosage has not been established. Biomechanical changes to tissue are known indicators for tumor diagnosis due to its association with the structural organization and composition of tissues at the cellular and molecular level. Here, by exploiting the theranostic functionality of magnetic nanoparticles (MNPs), we aim to explore the potential of using stiffness-based metrics that reveal the intrinsic biophysical changes of in vivo melanoma tumors after MH therapy. Methods: A total of 14 melanoma-bearing mice were intratumorally injected with dextran-coated MNPs, enabling MH treatment upon the application of an alternating magnetic field (AMF) at 64.7 kHz. The presence of the MNP heating sources was detected by magnetomotive optical coherence tomography (MM-OCT). For the first time, the elasticity alterations of the hyperthermia-treated, MNP-laden, in vivo tumors were also measured with magnetomotive optical coherence elastography (MM-OCE), based on the mechanical resonant frequency detected. To investigate the correlation between stiffness changes and the intrinsic biological changes, histopathology was performed on the excised tumor after the in vivo measurements. Results: Distinct shifts in mechanical resonant frequency were observed only in the MH-treated group, suggesting a heat-induced stiffness change in the melanoma tumor. Moreover, tumor cellularity, protein conformation, and temperature rise all play a role in tumor stiffness changes after MH treatment. With low cellularity, tumor softens after MH even with low temperature elevation. In contrast, with high cellularity, tumor softening occurs only with a low temperature rise, which is potentially due to protein unfolding, whereas tumor stiffening was seen with a higher temperature rise, likely due to protein denaturation. Conclusions: This study exploits the theranostic functionality of MNPs and investigates the MH-induced stiffness change on in vivo melanoma-bearing mice with MM-OCT and MM-OCE for the first time. It was discovered that the elasticity alteration of the melanoma tumor after MH treatment depends on both thermal dosage and the morphological features of the tumor. In summary, changes in tissue-level elasticity can potentially be a physically and physiologically meaningful metric and integrative therapeutic marker for MH treatment, while MM-OCE can be a suitable dosimetry technique.

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Magnetic and contrast properties of labeled platelets for magnetomotive optical coherence tomography.

Publications

Magnetic and contrast properties of labeled platelets for magnetomotive optical coherence tomography.

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