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

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.

[1]  J. Moake,et al.  Platelets and shear stress. , 1996, Blood.

[2]  S. Nie,et al.  Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy , 2008, International journal of nanomedicine.

[3]  Brett E. Bouma,et al.  In Vivo Characterization of Coronary Atherosclerotic Plaque by Use of Optical Coherence Tomography , 2005, Circulation.

[4]  W. Nichols McDonald's Blood Flow in Arteries , 1996 .

[5]  K. Hatakeyama,et al.  Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans , 2005, Heart.

[6]  David D Sampson,et al.  Quantitative upper airway imaging with anatomic optical coherence tomography. , 2006, American journal of respiratory and critical care medicine.

[7]  T. Fischer,et al.  Primary and secondary hemostatic functionalities of rehydrated, lyophilized platelets , 2006, Transfusion.

[8]  D. Wagner,et al.  The P‐selectin, tissue factor, coagulation triad , 2005, Journal of thrombosis and haemostasis : JTH.

[9]  T. Fischer,et al.  Correction of the Bleeding Time With Lyophilized Platelet Infusions in Dogs on Cardiopulmonary Bypass , 2008, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[10]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[11]  D. Yablonskiy,et al.  Water proton MR properties of human blood at 1.5 Tesla: Magnetic susceptibility, T1, T2, T  *2 , and non‐Lorentzian signal behavior , 2001, Magnetic resonance in medicine.

[12]  J. White Platelets are covercytes, not phagocytes: Uptake of bacteria involves channels of the open canalicular system , 2005, Platelets.

[13]  Amy L Oldenburg,et al.  Imaging magnetically labeled cells with magnetomotive optical coherence tomography. , 2005, Optics letters.

[14]  W. van Aken,et al.  Platelet Aggregation: an Intermediary Mechanism in Carbon Clearance , 2009 .

[15]  K. Tanoue,et al.  Electron microscopic observations on platelet aggregation induced by cationized ferritin. , 1983, Blood.

[16]  D. Bellinger,et al.  Preservation of hemostatic and structural properties of rehydrated lyophilized platelets: potential for long-term storage of dried platelets for transfusion. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Joseph A. Izatt,et al.  Spectral domain phase microscopy , 2004 .

[18]  T. Fischer,et al.  SPLENIC CLEARANCE MECHANISMS OF REHYDRATED, LYOPHILIZED PLATELETS , 2001, Artificial cells, blood substitutes, and immobilization biotechnology.

[19]  Christodoulos Stefanadis,et al.  Vascular wall shear stress: basic principles and methods. , 2005, Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese.

[20]  K. Jurk,et al.  Platelets: Physiology and Biochemistry , 2005, Seminars in thrombosis and hemostasis.

[21]  J. White Why human platelets fail to kill bacteria , 2006, Platelets.

[22]  Freddy T. Nguyen,et al.  Optical coherence tomography: a review of clinical development from bench to bedside. , 2007, Journal of biomedical optics.

[23]  Arend Heerschap,et al.  Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy , 2005, Nature Biotechnology.

[24]  J. Leor,et al.  Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium , 2007, Circulation.

[25]  E. Elster,et al.  Evaluation of lyophilized platelets as an infusible hemostatic agent in experimental non‐compressible hemorrhage in swine , 2009, Journal of thrombosis and haemostasis : JTH.

[26]  Maciej Wojtkowski,et al.  High-definition and 3-dimensional imaging of macular pathologies with high-speed ultrahigh-resolution optical coherence tomography. , 2006, Ophthalmology.

[27]  L. Brush,et al.  McDonaldʼs Blood Flow in Arteries , 1991 .

[28]  Samuel A Wickline,et al.  Nanotechnology for molecular imaging and targeted therapy. , 2003, Circulation.

[29]  G. Koch,et al.  Porphyromonas gingivalis Bacteremia Induces Coronary and Aortic Atherosclerosis in Normocholesterolemic and Hypercholesterolemic Pigs , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[30]  P. Joy,et al.  Comparison of the zero-field-cooled magnetization behavior of some ferromagnetic and ferrimagnetic systems , 2000 .

[31]  J. White Uptake of latex particles by blood platelets: phagocytosis or sequestration? , 1972, The American journal of pathology.

[32]  Amy L Oldenburg,et al.  Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues. , 2008, Optics express.

[33]  J. White,et al.  Platelet interaction with bacteria. II. Fate of the bacteria. , 1971, The American journal of pathology.

[34]  P. Tracqui,et al.  Standardization of a method for characterizing low-concentration biogels: elastic properties of low-concentration agarose gels. , 1999, Journal of biomechanical engineering.

[35]  Philippe Robert,et al.  Recent advances in iron oxide nanocrystal technology for medical imaging. , 2006, Advanced drug delivery reviews.

[36]  P. Wust,et al.  Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles , 1999 .

[37]  R. John,et al.  In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes , 2010, Proceedings of the National Academy of Sciences.

[38]  R. Reddick,et al.  Thrombotic thrombocytopenia with von Willebrand factor deficiency induced by botrocetin. An animal model. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[39]  F. N. van de Vosse,et al.  The mechanical role of thrombus on the growth rate of an abdominal aortic aneurysm. , 2010, Journal of vascular surgery.

[40]  V. Rotello,et al.  Direct control of the magnetic interaction between iron oxide nanoparticles through dendrimer-mediated self-assembly. , 2005, Journal of the American Chemical Society.

[41]  I. Sarov,et al.  Interaction between vaccinia virus and human blood platelets. , 1982, Blood.

[42]  Q. Pankhurst,et al.  Superconducting quantum interference device measurements of dilute magnetic materials in biological samples , 2005 .

[43]  M. Read,et al.  Lyophilized platelets: continued development. , 2000, Transfusion science.

[44]  J. Fujimoto,et al.  Optical Coherence Tomography , 1991, LEOS '92 Conference Proceedings.

[45]  K. Huber,et al.  Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease , 2002, British journal of haematology.

[46]  Barry Cense,et al.  Advances in optical coherence tomography imaging for dermatology. , 2004, The Journal of investigative dermatology.

[47]  S Chien,et al.  In vivo measurements of "apparent viscosity" and microvessel hematocrit in the mesentery of the cat. , 1980, Microvascular research.

[48]  Nathalie Siauve,et al.  Liver Imaging With Ferumoxides (Feridex®): Fundamentals, Controversies, and Practical Aspects , 1998, Topics in magnetic resonance imaging : TMRI.

[49]  C. Clawson Platelet interaction with bacteria. 3. Ultrastructure. , 1973, The American journal of pathology.