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Quantitative molecular imaging of angiogenesis-targeted fluorinated nanoparticles: new approaches for B1-mapping compensation for 19F-MRI


Quantitative MR molecular imaging allows for the detection of targeted contrast agents to diagnose disease states and monitor response to therapy, such as anti-angiogenic therapy in atherosclerosis and cancer with ανβ3-integrin targeted perfluorocarbon (PFC) nanoparticles. Recently, 19F MR using a 19F/1H dual-tuned RF coil has been utilized to directly image and quantify the fluorinated core of these PFC nanoparticle (NP) emulsions. However, low concentrations of these fluorine agents in the body, in conjunction with varying RF coil sensitivity profiles (B1-field inhomogeneities) raise obstacles to accurate quantification. This study presents a strategy to more accurately quantify the sparse 19F signal from PFC NP emulsions with a 1H image-based Actual Flip-angle Imaging (AFI) B1-mapping correction to the 19F and 1H images.


New Zealand White Rabbits (2 kg) were implanted with a VX2 adenocarcinoma tumor (2-3 cm) in the hind leg. Angiogenesis imaging was performed 2 weeks post implantation, under ketamine/xylazine anesthesia. An ανβ3-integrin targeted perfluoro-octyl bromide (PFOB) nanoparticle emulsion was prepared, and injected intravenously 3 hours before imaging. MR data were acquired on a 3T clinical whole-body scanner (Achieva, Philips Healthcare) with a dual 19F/1H spectrometer system and a dual-tuned transmit/receive single loop surface RF coil (7×12 cm). A simultaneous 19F/1H gradient echo (GRE) imaging sequence was used with: 19F offset frequency on the center of the PFOB CF2 peak, 15 4-mm slices, 140 mm FOV, 483 matrix, α = 60°, TE/TR = 2.2/8.5 ms, 21 min scan time. The B1 field was mapped using an AFI sequence with matching geometry. Using the flip angle map and a model of the GRE signal, a spatially-dependent calibration mask was calculated in MATLAB (MathWorks) and used to compensate the 1H and 19F signal intensities for the GRE sequence.


PFC NP targeted the tumor neovasculature, and provided localized 19F signal as expected. Figure 1 displays the uncorrected (top) and corrected (bottom) 1H images with the 19F signal superimposed, using the AFI (middle) B1-mapping correction technique. After correction, the 1H signal intensity profile as a function of distance from the surface coil (located at right) is improved. After the same correction to the 19F signal, the measured concentration of nanoparticles when compared to a standard was 10.2 ± 1.0 mM19F, versus 9.0 ± 2.2 mM19F before correction.

Figure 1
figure 1

Top: uncorrected 1H image of rabbit model with angiogenesis-targeted 19F imaging (blue overlay). Middle: AFI B1 map (% actual/requested flip angle). Bottom: 1H and 19F superimposed images using AFI B1-mapping correction.


An image-based B1-mapping correction acquired with 1H can be used to correct signal intensities for 19F and 1H images of angiogenesis in an in vivo rabbit model. The correction results in a more homogeneous 1H image of the anatomy and facilitates accurate measurement of bound ανβ3-integrin targeted nanoparticles with 19F imaging.


AHA 11PRE7530046; NIH R01 HL073646.

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Goette, M.J., Schmieder, A.H., Williams, T.A. et al. Quantitative molecular imaging of angiogenesis-targeted fluorinated nanoparticles: new approaches for B1-mapping compensation for 19F-MRI. J Cardiovasc Magn Reson 15 (Suppl 1), O83 (2013).

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