Please cite this paper as: Deloison B, Siauve N, Aimot S, Balvay D, Thiam R, Cuenod C, Ville Y, Clement O, Salomon L. SPIO‐enhanced magnetic resonance imaging study of placental perfusion in a rat ...model of intrauterine growth restriction. BJOG 2012;119:626–633.
Objective To assess placental perfusion with magnetic resonance imaging (MRI) and superparamagnetic iron oxide (SPIO) in a rat model of intrauterine growth restriction (IUGR).
Design Experimental animal study.
Setting The study complied with US National Institutes of Health recommendations for animal care.
Population Thirty‐two rats at day 16 of gestation underwent surgical ligation of the left uterine vessel to induce IUGR.
Methods Eighteen rats were examined by MRI 3 days later, after bolus injection of ferucarbotran.
Main outcome measure Signal intensities were measured in the maternal left ventricle and in the placentas of the two horns. Quantitative microcirculation parameters were calculated and compared between the placentas of the two horns.
Results Fifty‐four kinetic curves of placental perfusion were obtained in 11 rats. The mean placental blood flow was significantly lower in the ligated horns than in the normal horns (108.1 versus 159.4 ml/minute/100 ml, p = 0.0004). The mean fractional volume of the maternal vascular placental compartment did not differ significantly between the pathological (42.8%) and normal placentas (39.2%).
Conclusions Placental perfusion, including changes during experimental IUGR, can be measured in rats by using MRI with SPIO. These findings could have implications for human studies of placental microcirculation and for the management of disorders related to placental dysfunction.
To determine whether computed tomography (CT) can depict liver hemodynamic changes caused by occult hepatic micrometastases in rat.
Liver micrometastases (mean diameter, 500 micrometer +/- 300) were ...produced in seven BD IX rats by injecting 10(7) DHDK12 PROb colorectal carcinoma cells into the spleen. Macrometastases (mean diameter, 7 mm +/- 3) were produced in four other rats. Five normal rats were studied as controls. CT images were obtained every 300 msec for 30 seconds during the injection of 1 mL per kilogram of body weight of contrast medium. The time-attenuation curves of the aorta, portal vein, and liver were used to calculate liver perfusion with a deconvolution model designed for the dual blood supply.
Micrometastases in an apparently normal liver caused a 34% decrease in portal blood flow and a 25% increase in the mean transit time for the blood to pass through the liver. These findings suggest increased resistance in the sinusoidal capillaries. Similar but greater changes were found in the macrometastases.
Occult liver micrometastases in rats generate changes in liver perfusion that can be detected with CT.
This study was designed to evaluate prospectively magnetic resonance imaging for the prediction of the circumferential resection margin in rectal cancer to identify in which patient magnetic ...resonance imaging could accurately assess the circumferential resection margin before surgery and in which patients it could not.
During a 17-month period, a preoperative magnetic resonance imaging for the assessment of circumferential resection margin was obtained prospectively in 38 patients with mid or low rectal cancer. The agreement of magnetic resonance imaging and pathologic examination for assessment of circumferential resection margin was analyzed.
Overall, magnetic resonance imaging agreed with histologic examination of the circumferential resection margin assessment in 28 patients (73 percent; kappa = 0.47). In all cases of disagreement between magnetic resonance imaging and pathology, magnetic resonance imaging overestimated the circumferential resection margin involvement. For the 11 patients with mid rectal cancer, circumferential resection margin was well predicted by magnetic resonance imaging in all cases (kappa = 1). For 27 patients with low rectal tumor, overall agreement between magnetic resonance imaging and histologic assessment was 63 percent (kappa = 0.35). Agreement was 22 percent (kappa = 0.03) for the 9 patients with low anterior and 83 percent (kappa = 0.67) for the 18 patients with low posterior rectal tumor. Univariate analysis revealed that only low and anterior rectal tumor was risk factor of overestimation of the circumferential resection margin by magnetic resonance imaging.
Although magnetic resonance imaging remains the best imaging tool for the preoperative assessment of the circumferential resection margin in patients with rectal cancer, it can overestimate the circumferential resection margin involvement in low and anterior tumor with the risk of overtreating the patients.
Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and ...cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy.
Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison.
fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully.
fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.
To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the ...targeting of overexpressed glucose receptors.
Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine NPG), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test.
In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 SD, 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2).
Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.
We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial ...growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.
We assessed the capacity of chest radiography and CT to determine the cause and site of bleeding in patients with either large or massive hemoptysis compared with bronchoscopy.
We reviewed the chest ...radiographs, CT scans, and bronchoscopic findings in 80 patients with either large or massive hemoptysis who were admitted to our intensive care unit between January 1995 and June 1999.
Findings on chest radiography were normal in only 13% of patients, of whom 70% had bronchiectasis. The chest radiographs revealed the site of bleeding in 46% of the patients and the cause in 35%, most of whom had tuberculosis or tumors. CT was more efficient than bronchoscopy for identifying the cause of bleeding (77% vs 8%, respectively; p < 0.001), whereas the two methods were comparable for identifying the site of bleeding (70% vs 73%, respectively; p = not significant).
These data suggest that CT could replace bronchoscopy as the first-line procedure for screening patients with large and those with massive hemoptysis. However, these results must be confirmed in a prospective multicenter study.
Macromolecular contrast-enhanced functional CT was performed to characterize early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with chemically induced primary liver tumors ...ranging pathologically from hyperplasia to HCC and 15 control rats were investigated. Two dynamic CT scans using an experimental macromolecular contrast agent were performed on a single slice 11 and 18 weeks after tumor induction followed by pathological examination. A deconvolution mathematical model was applied, yielding the hepatic perfusion index (HPI), mean transit time (MTT), liver distribution volume (LDV) and arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC. On the first scans, HCC at an early pathological stage had a low FP (-30%, P=0.002) but a normal arterial-portal balance. On the scan contemporary to pathology, HCC perfusion parameters showed an inversion of the arterial-portal balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (-69%, P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even though only one (7%) was visible to the eye. Perfusion-CT allowed early detection of HCC. This technique could contribute in the detection and characterization of liver lesions in clinical studies.
To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. ...Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/alpha 13 ms/1.2 ms/60 degrees ) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume Vdistribution, volume transfer constant Ktrans, rate constant of influx kpe, and initial extraction (fraction) E. Tumor perfusion was F=43+/-29 ml.min-1.100 g-1. The permeability study allowed the measurement of kpe=0.37+/-0.12 min-1 and Ktrans=0.01+/-0.0031 min-1. The blood volume could be assimilated to the distribution volume (Vdistribution=2.9+/-1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34+/-1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization.
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