Intraindividual comparison of gadobenate dimeglumine and gadobutrol for cerebral magnetic resonance perfusion imaging at 1.5 T.

RATIONALE AND OBJECTIVE: The objective of this study was to compare 0.1 and 0.2 mmol/kg body weight (bw) doses gadobenate dimeglumine (Gd-BOPTA; MultiHance) and gadobutrol (Gd-BT-DO3A; Gadovist) for cerebral perfusion magnetic resonance (MR) imaging at 1.5 T. METHODS: Twelve healthy male volunteers enrolled into a randomized intraindividual comparative study underwent 4 perfusion MR imaging examinations with 0.1 and 0.2 mmol/kg bw doses of each contrast agent. The imaging parameters, slice positioning, and contrast agent application were highly standardized. Quantitative determinations based on signal intensity/time (SI/T) curves at regions of interest (ROI) on the gray and white matter were made of the regional cerebral blood volume and flow (rCBV and rCBF, respectively), the percentage signal drop, and the full width half maximum (FWHM) of the SI/T curve. Qualitative evaluation of the quality of the rCBV and rCBF maps was assessed by an independent offsite blinded reader. RESULTS: A single dose of both agents was sufficient to achieve high-quality, diagnostically valid perfusion maps at 1.5 T, and no significant benefit for one agent over the other was noted for quantitative or qualitative determinations. The susceptibility effect, described by percentage of signal loss (gadobutrol: 29.4% vs gadobenate dimeglumine: 28.3%) and the FWHM (gadobutrol: 6.4 seconds vs gadobenate dimeglumine: 7.0 seconds) were similar for 0.1 mmol/kg bw doses of the 2 agents. Double doses of the 2 agents produced better overall image quality but no clinical benefit over the single-dose examinations. CONCLUSION: Both the 1 molar MR contrast agent gadobutrol and the weak protein-interacting agent gadobenate dimeglumine permit the acquisition of high-quality perfusion maps at doses of 0.1 mmol/kg bw. The susceptibility effect is comparable for both agents and stronger than for conventional MR contrast agents.

Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison.

RATIONALE: Superparamagnetic iron-oxide particles are used frequently for cellular magnetic resonance imaging and in vivo cell tracking. The purpose of this study was to compare the labeling characteristics and efficiency as well as toxicity of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) for 3 cell lines. METHODS: Using human fibroblasts, immortalized rat progenitor cells and HEP-G2-hepatoma cells, dose- and time-dependence of SPIO and USPIO uptake were evaluated. The amount of intracellular (U)SPIO was monitored over 2 weeks after incubation by T2-magnetic resonance relaxometry, ICP-mass-spectrometry, and histology. Transmission-electronmicroscopy was used to specify the intracellular localization of the endocytosed iron particles. Cell death-rate and proliferation-index were assessed as indicators of cell-toxicity. RESULT: For all cell lines, SPIO showed better uptake than USPIO, which was highest in HEP-G2 cells (110 +/- 2 pg Fe/cell). Cellular iron concentrations in progenitor cells and fibroblasts were 13 +/- 1pg Fe/cell and 7.2 +/- 0.3pg Fe/cell, respectively. For all cell lines T2-relaxation times in cell pellets were below detection threshold (<3 milliseconds) after 5 hours of incubation with SPIO (3.0 micromol Fe/mL growth medium) and continued to be near the detection for the next 6 days. For both particle types and all cell lines cellular iron oxide contents decreased after recultivation and surprisingly were found lower than in unlabeled control cells after 15 days. Viability and proliferation of (U)SPIO-labeled and unlabeled cells were not significantly different. CONCLUSIONS: The hematopoetic progenitor, mesenchymal fibroblast and epithelial HEP-G2 cell lines accumulated SPIO more efficiently than USPIO indicating SPIO to be better suited for cell labeling. However, the results indicate that there may be an induction of forced cellular iron elimination after incubation with (U)SPIO.

Improved correlation of histological data with DCE MRI parameter maps by 3D reconstruction, reslicing and parameterization of the histological images.

Due to poor correlation of slice thickness and orientation, verification of radiological methods with histology is difficult. Thus, a procedure for three-dimensional reconstruction, reslicing and parameterization of histological data was developed, enabling a proper correlation with radiological data. Two different subcutaneous tumors were examined by MR microangiography and DCE-MRI, the latter being post-processed using a pharmacokinetic two-compartment model. Subsequently, tumors were serially sectioned and vessels stained with immunofluorescence markers. A ray-tracing algorithm performed three-dimensional visualization of the histological data, allowing virtually reslicing to thicker sections analogous to MRI slice geometry. Thick slices were processed as parameter maps color coding the marker density in the depth of the slice. Histological 3D reconstructions displayed the diffuse angioarchitecture of malignant tumors. Resliced histological images enabled specification of high enhancing areas seen on MR microangiography as large single vessels or vessel assemblies. In orthogonally reconstructed histological slices, single vessels were delineated. ROI analysis showed significant correlation between histological parameter maps of vessel density and MR parameter maps (r=0.83, P=0.05). The 3D approach to histology improves correlation of histological and radiological data due to proper matching of slice geometry. This method can be used with any histological stain, thus enabling a multivariable correlation of non-invasive data and histology.

Low mechanical index contrast-enhanced ultrasound better reflects high arterial perfusion of liver metastases than arterial phase computed tomography.

RATIONALE AND OBJECTIVES: We investigated whether observing the arterial vascularization of liver metastases by contrast-enhanced ultrasound with low mechanical index (low-MI) imaging offers additional diagnostic information for the characterization of the liver lesions. METHODS: Twenty nine patients with untreated liver metastases of different primaries were examined. Measurements were performed using a low frame rate, low-MI pulse inversion technique after injection of 2.4 mL SonoVue. The relative maximum signal intensity of the liver lesions related to the normal liver tissue was quantified. Ultrasound findings were compared with contrast-enhanced, dual-phase computed tomography (CT) using a pattern-based classification scheme. RESULTS: Compared with contrast-enhanced CT, this modality better detects arterial perfusion. Metastases, even those usually considered hypovascularized, often showed homogeneous enhancement (66%) and higher arterial vascularization than normal liver tissue. CT did not show a comparable vascularization pattern (P < 0.001) or any similarly early signal intensity (P < 0.001). CONCLUSIONS: Contrast-enhanced CT may not be able to visualize short-lasting but large differences of the arterial perfusion of liver metastases, as does contrast-enhanced low-MI ultrasound. This offers new methods for their characterization and for monitoring of therapeutic effects.

Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumour perfusion in small animals.

Replenishment kinetics of microbubbles were adapted to a single bolus injection to investigate tumour angiogenesis in small animals with intermittent imaging, and to compare vascularisation parameters from this new approach with conventional power Doppler ultrasound (US). A reformulation of the imaging protocol and the derivation of perfusion parameters was necessary, taking into account the time-dependence of the systemic microbubble concentration after single bolus injection. Using this new method, tumour vascularisation was evaluated in 13 experimental murine tumours. Furthermore, parameters calculated with intermittent imaging after bolus injection of 100 microl Levovist were compared with parameters from the signal intensity-time curve. The results showed that quantifying tumour perfusion, blood volume and flow, as well as the assessment of the mean blood velocity (in m/s), is possible in tumours with a volume of more than 0.1 mL. In larger tumours, a lower perfusion was calculated than in smaller ones (k = -0.88; p < 0.001). Only limited correlations were found between conventional power Doppler US quantities and parameters of intermittent sonography: Perfusion correlated with the maximum signal intensity (k = 0.61, p < 0.05) and the gradient to maximum (k = 0.82, p < 0.01), full width-half maximum was associated with blood volume (k = 0.62, p < 0.05). We conclude that intermittent bolus contrast sonography allows the quantification of tumour perfusion, even in small animals, and the monitoring of basic antiangiogenic studies with perfusion parameters shows a higher significance than conventional power Doppler US.