Quantitative magnetic resonance fluorine imaging: today and tomorrow

(a) Representative ¹⁹F spectrum of perfluoropolyether (PFPE) and perfluorooctylbromide (PFOB) nanoparticles shows the chemical shift of ¹⁹F signatures. The single PFPE peak and five discernible PFOB peaks are easily detected and individually resolved. (b) Chemical structure of PFPE shows its 20 ¹⁹F atoms. (c) Schematic of a PFPE nanoparticle functionalized with homing ligands in the outer phospholipid monolayer (shown in green). The PFPE nanoparticle provides ¹H magnetic resonance (MR) contrast by its surface payload of ∼90, 000 Gd³⁺ (shown in gold) and ¹⁹F MR contrast by ∼100 M ¹⁹F in its core. (Reprinted with permission from Ref 10. Copyright 2004 John Wiley & Sons, Inc. and Ref 11. Copyright 2009 Elsevier).

Localization of perfluorocarbon (PFC) nanoparticles labeled cells in mice using ¹⁹F magnetic resonance imaging (MRI). (a) ¹⁹F MRI trafficking of stem/progenitor cells labeled with either perfluorooctylbromide (PFOB) (green) or perfluoropolyether (PFPE) (red) nanoparticles. Labeled cells were locally injected into the skeletal muscle of mouse thigh before MRI. (b)–(d) At 11.7‐T field strength, ¹⁹F spectral discrimination permits respective imaging of ∼1 × 10⁶ PFOB‐loaded cells (b) and PFPE‐loaded cells (c). The composite ¹⁹F (displayed in color) and ¹H (displayed in grayscale) images (d) reveal the location of PFOB labeled cells in the left leg and PFPE labeled cells in the right leg (dashed line indicates 3 × 3 cm² field of view for ¹⁹F images). (e) Similarly, a ¹⁹F image acquired at 1.5‐T field strength shows ¹⁹F signal from ∼4 × 10⁶ PFPE nanoparticles labeled cells. (f) The composite ¹⁹F and ¹H images show the location of PFPE nanoparticles labeled cells in a mouse thigh. Overall, the absence of background signal in ¹⁹F images (b), (c), and (e) enables unambiguous localization of PFC‐containing cells at both 1.5 and 11.7 T field strength. (Reprinted with permission from Ref 67. Copyright 2007 FASEB).

Fluorocarbon relaxometry using echo planar imaging for dynamic oxygen mapping determined pO₂ maps of two representative AT1 tumors in rats. The pO₂ value was calculated pixel‐by‐pixel based on the quantified ¹⁹F R₁ and a priori calibrated ¹⁹F R₁–pO₂ curve of hexafluorobenzene (HFB). (a) and (d) Composite ¹⁹F (displayed in color) and ¹H (displayed in grayscale) magnetic resonance images show HFB distribution in a large tumor (a, 3.6 cm³) and a small tumor (d, 1 cm³). (b) and (e) Baseline pO₂ maps show higher pO₂ in the small tumor when both animals were breathing air. Mean pO₂ of large and small tumors was 0.1 ± 1.8 and 25.4 ± 1.1 torr, respectively. (c) and (f) Tumor pO₂ maps of the same animals obtained at 24 min after oxygen breathing; mean pO₂ of large and small tumors was 8.1 ± 4.5 and 90.6 ± 3.9 torr, respectively. Both values were significantly higher than that of baseline (p < 0.01). (Reprinted with permission from Ref 52. Copyright 2007 Elsevier).

(a) A representative ¹⁹F spectrum of perfluoropolyether (PFPE) nanoparticle emulsion (−90 ppm) and trichlorofluoromethane reference standard (0 ppm) acquired at 4.7 T. (b) The calibration curve for PFPE nanoparticle emulsion shows a linear relationship between the quantity of perfluorocarbon nanoparticles and ¹⁹F signal intensity. (c) Left: an optical image of a human carotid endarterectomy sample shows moderate luminal narrowing and several atherosclerotic lesions. Middle: a ¹⁹F projection image acquired through the entire thickness of carotid artery sample shows high ¹⁹F signal along the lumen because of the binding of nanoparticles to fibrin. Right: The calculated concentration map of bound nanoparticles in the carotid sample based on ¹⁹F signal intensity in each voxel and the calibrated standard curve in (b). (Reprinted with permission from Ref 10. Copyright 2004 John Wiley & Sons, Inc.).

Diffusion weighted ¹⁹F signal in the ear of K14‐HPV16 mice (open symbols), an animal model of squamous cell cancer with dysplastic lesions developed in the ear epidermis, and in the ear of control C57BL/6 mice (filled symbols). All animals were intravenously injected with α_vβ₃‐integrin targeted perfluorocarbon nanoparticles before magnetic resonance imaging. (a) Results show complete decay of ¹⁹F signal in control mouse ears when b value (i.e., an index of diffusion weighting) is > 1500 s/mm². In contrast, a large fraction of ¹⁹F signal persisted in the ears of K14‐HPV16 mice at all b values, reflecting the specific binding of targeted nanoparticles to the ear neovasculature of K14‐HPV16 mice. (b) Diffusion weighted ¹⁹F signal in the ears of K14‐HPV16 mice persisted even when b values are > 10,000 s/mm². (Reprinted with permission from Ref 55. Copyright 2008 John Wiley & Sons, Inc.).