Article
Nanoscaled liposomes increase homogeneity in contrast enhanced ultrasound imaging
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Published: | September 16, 2010 |
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Objective: In neurosurgery ultrasound (US) contrast enhanced imaging is used in brain perfusion measurement or in the diagnosis of vasospasm after subarachnoidal hemorrhage. Texture and homogeneity of contrast enhanced US is a crucial criteria of image quality in brightness mode e.g. in cerebral tumor imaging. The aim of our study was to examine the contrast properties of ideally sized 100 nm liposomes made of dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and polyethyleneglycol-40stearate (PEG-40-STEA) compared to the commercial available SonoVue. To obtain texture and homogeneity of US images, the box-counting fractal dimension D_B and lacunarity lambda (l) was used in this study.
Methods: Phased inversion harmonic imaging of a medical US device (Siemens SonoLine Elegra) equipped with a 2.5 MHz phased array transducer was used to measure the second harmonics of the samples in a flow model. Fundamental frequency was 1.4 MHz with a MI of 0.4. US images of 8, 10, 12, 16, 30 and 60 seconds after administration of the liposomes were digitally preprocessed to obtain white spots on a black background that indicates contrast enhancement. A variable (e) was computed as box-size divided by image-size. The number of pixels in each (e)-sized box was counted and (l) for each grid was calculated from the standard deviation and mean. Slopes of (l) were used for statistics. Low slope values indicate homogeneity of digital images, high values of DB indicate minimal alterations in texture.
Results: Lowest slope values were obtained from DPPC/PEG-40-STEA. We found significant lower (l) values compared to SonoVue (p<0.01) for the first 30 seconds of insonation. We found no significant differences in lacunarity within the DPPC/PEG-40-STEA time-series (p=0.95). Highest values of lacunarity were obtained from DPPC/CHOL. For DPPC/PEG-40-STEA we found slightly changes in DB during insonation. Our results could be explained by the modelling of the Rayleigh-Plesset-equation. The resonance frequency of a microbubble is inversely proportional to the bubble radius and proportional to the shell stiffness.
Conclusions: The nanoscaled DPPC/PEG-40-STEA could be a promising contrast agent in US diagnostics e.g. of vascularisation in intracerebral tumors, target drug delivery, and functional US in ischemic diseases like stroke or cerebral vasospasm. Furthermore, D_B and (l) could be a valid and reliable mathematical tool to describe contrast enhanced US imaging.