Ultrasound derived imaging and quantification of cell adhesion molecules in experimental autoimmune encephalomyelitis (EAE) by Sensitive Particle Acoustic Quantification (SPAQ)

Reinhardt, Michaël; Hauff, Peter; Linker, Ralf A.; Briel, Andreas; Gold, Ralf; Rieckmann, Peter; Becker, Georg; Toyka, Klaus V.; Mäurer, Mathias; Schirner, Michael

doi:10.1016/j.neuroimage.2005.04.019

Cited by 32 publications

(25 citation statements)

References 32 publications

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“…ICAM-1 targeted MP emit a typical periventricular signal (Fig. 1C), that is comparable to the ICAM-1 specific signal pattern found in the ex vivo approach [7]. The ultrasound device is coupled to an automatic video densitometry system for quantification of SAE signals.…”

Section: Experimental Set-upsupporting

confidence: 62%

“…Molecular imaging with ultrasound now further extends the spectrum of molecular imaging technologies. In particular, the application of the SPAQ technology in combination with target specific ultrasound contrast media [7,9] provides a high spatial resolution within the micrometer range and enables a reliable quantification. The cost-effectiveness as well as the broad availability of ultrasound devices may further support its (pre)clinical acceptance.…”

Section: Discussionmentioning

confidence: 99%

“…In an ex vivo approach, we specifically depicted the molecular pattern of ICAM-1 expression during autoimmune inflammation of the CNS with high sensitivity [7]. This method is based on a specific acoustic property of gasfilled MP, the stimulated acoustic emission effect (SAE) which allows visualization of MP in a color-coded 2D image [8].…”

Section: Introductionmentioning

confidence: 99%

“…Based on the SAE effect, we recently developed a method for the reliable quantification of ultrasound contrast media termed sensitive particle acoustic quantification (SPAQ) [9]. The detection of ICAM-MP elicited SAE effects by SAPQ enhanced ultrasound allows the reliable quantification of ICAM-1 expression ex vivo while at the same time increasing the resolution down to the micrometer range [7].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE)

Linker

Reinhardt²,

Bendszus

et al. 2005

Journal of Autoimmunity

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Section: Experimental Set-upsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE)

Linker

Reinhardt²,

Bendszus

et al. 2005

Journal of Autoimmunity

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“…VCAM-1 has been imaged previously using MPIO;[15] nanoparticles of iron oxide;[23] and acoustic microbubbles[24], [25] Although the contrast effects can be quantified, these earlier studies did not investigate whether there was a quantitative relationship between non-invasive contrast measurements and tissue levels of target. Micron-size range iron oxide-based molecular imaging probes provide both greatly enhanced sensitivity due to their high iron content and, because of their uniform size and composition, an opportunity for quantitative evaluation.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Quantification of Vcam-1 Expression in Renal Ischemia Reperfusion Injury Using Non-Invasive Magnetic Resonance Molecular Imaging

et al. 2010

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Rationale and ObjectiveVascular cell adhesion molecule-1 (VCAM-1) is upregulated in ischemia reperfusion injury (IRI), persisting after restoration of blood flow. We hypothesized that microparticles of iron oxide targeting VCAM-1 (VCAM-MPIO) would depict “ischemic memory” and enable in vivo assessment of VCAM-1 expression.Methodology and FindingsMice subject to unilateral, transient (30 minutes) renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO (4.5 mg iron/kg body weight). Contrast agent bound rapidly (<30 minutes) in IRI-kidneys and appeared as intensely low signal areas by MRI in vivo. Automated segmentation and quantification yielded MPIO contrast volumes of 5991±354×106 µm3 in IRI vs. 87±7×106 µm3 in kidneys with no surgical intervention (P<0.001); 90±8×106 µm3 in IRI kidneys exposed to control (IgG-MPIO) and 625±80×106 µm3, in IRI kidneys pre-treated with a blocking dose of VCAM-1 antibody (P<0.001). In keeping with quantitative MRI data, VCAM-1 mRNA expression in IRI was 65-fold higher than in kidneys without surgical intervention (3.06±0.63 vs. 0.05±0.02, P<0.001). Indeed VCAM-1 mRNA expression and VCAM-MPIO contrast volume were highly correlated (R2 = 0.901, P<0.01), indicating that quantification of contrast volume reflected renal VCAM-1 transcription. Serial imaging showed VCAM-MPIO accumulation at target within 30 minutes, persisting for ≥90 minutes, while unbound VCAM-MPIO was cleared rapidly from blood, with sequestration by mac-3 positive Kupffer cells in the liver and monocyte/macrophages in the spleen.Conclusions(1) VCAM-MPIO detected VCAM-1 expression and defined its 3-dimensional distribution, revealing “ischemic memory” in renal IRI; (2) automated volumetric quantification of VCAM-MPIO accurately reflected tissue levels of VCAM-1 mRNA; and (3) VCAM-MPIO bound rapidly to target with active sequestration of unbound MPIO in the liver and spleen.

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Characterization of thein vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion molecules

Ottoboni¹,

Short²,

Kerby³

et al. 2006

Contrast Media Mol Imaging

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We have developed novel adhesion molecule-targeted double-shelled microspheres which encapsulate nitrogen. We report in vitro targeting studies utilizing these microspheres conjugated to target-specific antibodies directed towards ICAM-1 and VCAM-1. In static adherence experiments, the adherence patterns of microspheres conjugated to three different monoclonal antibodies (two targeted to ICAM-1 and one to VCAM-1) to their target surfaces were very different. Maximum microsphere adherence at the lowest target and/or ligand densities was observed with the VCAM-1 system. Differences in target-specific adherence were also observed between anti-ICAM-1 and anti-VCAM-1 microsphere conjugates in flow adherence studies. Equilibrium binding studies of the target proteins in solution to the microsphere-bound ligands showed that the affinity constants of two microsphere-bound monoclonal antibodies for their target proteins are similar. Thus, ligand-target affinity is not the only determinant of microsphere adherence to the target surface in our systems. Shear stress was found to have an effect on the mean diameter of adhered microspheres; a decrease in the mean diameter with increasing shear was observed. The magnitude of this effect was dependent on both microsphere-bound ligand and target surface densities, with a more pronounced change at lower densities. Adhered microspheres were readily detectable using ultrasound at the lowest tested surface density of 40 mm(-2).

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Ultrasound derived imaging and quantification of cell adhesion molecules in experimental autoimmune encephalomyelitis (EAE) by Sensitive Particle Acoustic Quantification (SPAQ)

Cited by 32 publications

References 32 publications

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE)

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE)

In Vivo Quantification of Vcam-1 Expression in Renal Ischemia Reperfusion Injury Using Non-Invasive Magnetic Resonance Molecular Imaging

Characterization of thein vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion molecules

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