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Biomedical subjects

Guy Frija

Publications and source records attributed to Guy Frija.

17 recordsLinked to original sources

Placental perfusion and permeability: simultaneous assessment with dual-echo contrast-enhanced MR imaging in mice.

PURPOSE: To assess placental perfusion and permeability in mice with magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was conducted according to French law and National Institutes of Health recommendations for animal care. Twenty-two pregnant BALB/c mice were examined at 1.5 T with a single-section dual-echo fast spoiled gradient-echo sequence. Two injection protocols were used: monophasic injection (double the clinical dose of contrast agent) and biphasic injection (quadruple the clinical dose). Signal intensities (SIs) were measured in the maternal left ventricle, placenta, and fetus (n = 16). At these high gadolinium doses, a T2* effect correction was used. SIs were converted to gadolinium concentrations and were analyzed by using a three-compartment model. Quantitative microcirculation parameters were calculated. Results with the monophasic and biphasic protocols were compared, and final arterial concentrations determined with MR imaging were compared with those determined with atomic emission spectrophotometry by using the unpaired Student t test. RESULTS: Perfusion and permeability parameters for monophasic and biphasic injections were similar: Mean placental blood flow was 180 mL/min/100 g, mean permeability surface coefficient from maternal placental to fetal placental compartment was 10.3 x 10(-4) sec(-1) +/- 6.81 (standard deviation), mean permeability surface coefficient from fetal placental to maternal placental compartment was 4.65 x 10(-4) sec(-1) +/- 4.37, and mean fractional volume of the maternal vascular placental compartment was 36.5% +/- 0.9. Placental (146 vs 105 micromol/L, P < .004) and fetal (33.3 vs 19.1 micromol/L, P < .001) gadolinium concentrations were higher with the biphasic than with the monophasic protocol. Arterial gadolinium concentrations at MR imaging did not differ significantly from those at spectrophotometry for the monophasic (P = .254) or biphasic (P = .776) injection protocol. CONCLUSION: Placental perfusion and permeability can be measured in vivo by using high gadolinium doses and a dual-echo MR imaging sequence.

Animals↗

Software volumetric evaluation of doubling times for differentiating benign versus malignant pulmonary nodules.

OBJECTIVE: The purpose of our study was to evaluate the reliability of software-calculated doubling times for discerning malignant versus benign nodules. MATERIALS AND METHODS: CT lung analysis volumetric software was used to retrospectively calculate the doubling times of 63 solid noncalcified nodules by comparing nodule volumes on baseline and follow-up CT scans obtained a median of 3.7 months apart. A final diagnosis based on validated criteria was available for all 63 nodules. All CT examinations were performed with 1.25-mm-thick slices on a four-detector unit. Taking 500 days as the upper value for malignancies, we evaluated whether the software-calculated doubling times could be used to distinguish malignant from benign solid nodules. We also examined whether the relative volume variation of benign nodules correlated with initial nodule size, interscan interval, or differences in contrast administration or exposure parameters between baseline and follow-up CT. RESULTS: There were 52 benign and 11 malignant nodules. Benign nodules had a median doubling time of 947 days and a mean relative volume variation of -4.4% (range, -50% to 38%). Malignant nodules had a median doubling time of 117 days and a mean relative volume variation of 102% (22-462%). The sensitivity, specificity, and negative and positive predictive values of the volumetric software for diagnosing malignancy were 91% (95% confidence interval [CI], 0.59-1.00), 90% (95% CI, 0.79-0.97), 98% (95% CI, 0.89-1.00), and 67% (95% CI, 0.38-0.88), respectively. No correlation was found between the relative volume variation of benign nodules and their initial size, the interscan interval, or differences in contrast administration or exposure parameters between the two CT examinations. CONCLUSION: Software-calculated pulmonary nodule doubling times of more than 500 days have a 98% negative predictive value for the diagnosis of solid malignant pulmonary nodules. This method may be useful for diagnosing malignant pulmonary nodules on follow-up CT.

Adult↗

Placental perfusion MR imaging with contrast agents in a mouse model.

PURPOSE: To quantitatively analyze placental perfusion by using magnetic resonance (MR) imaging with contrast agents in a mouse model. MATERIALS AND METHODS: Study was conducted according to French law and in full compliance with National Institutes of Health recommendations for animal care. Thirty-six pregnant Balb/c mice at 16 days of gestation were injected intravenously with either a conventional or macromolecular gadolinium chelate, and 1.5-T single-section T1-weighted two-dimensional fast spoiled gradient-echo sequential MR imaging was then performed for 14 minutes. Images were analyzed qualitatively, and parametric map analysis was performed in the resultant 25 mice included in the study. Signal intensity was measured in maternal left ventricle (input function), placenta, and fetus on all images. After converting signal intensity into contrast agent tissue concentrations, a three-compartment model was developed with compartmental and numeric modeling software. Placental perfusion was calculated for conventional (n = 12) and macromolecular (n = 13) gadolinium chelates. Finally, placental and fetal gadolinium concentrations were assayed by means of atomic emission spectrophotometry (n = 15). Perfusion values and placental and fetal gadolinium concentrations for conventional and macromolecular chelates were compared by using an unpaired t test. RESULTS: Based on a constant transfer parameter, estimated placental perfusion did not differ between procedures with conventional and macromolecular gadolinium chelates (0.99 mL/min/g +/- 0.5 [standard deviation] and 1.28 mL/min/g +/- 0.6, respectively, P = .22). Likewise, mean placental gadolinium concentrations did not differ after injection of conventional and macromolecular chelates. In contrast, mean fetal gadolinium concentration was 9.83 micromol/L after conventional chelate injection and below detection limit after macromolecular chelate injection. CONCLUSION: Placental perfusion can be calculated by using dynamic contrast-enhanced MR imaging, as shown in this mouse model.

Animals↗

Diagnosing pulmonary embolism with four-detector row helical CT: prospective evaluation of 216 outpatients and inpatients.

PURPOSE: To prospectively evaluate multi-detector row helical computed tomography (CT) for the diagnosis of pulmonary embolism (PE), with focus on the proportion of diagnostic studies and frequency of subsegmental and chronic PE. MATERIALS AND METHODS: Institutional review board approval and patient consent were not required. A total of 220 consecutive CT angiography studies, 124 (56%) of which involved inpatients, were assessed. Thoracic CT angiography was performed in 216 patients; there were 101 male (age range, 25-93 years; median, 66 years) and 115 female (age range, 15-98 years; median, 67 years) patients. Contiguous 1.25-mm sections were acquired through the entire thorax after injection of 140 mL of contrast material at a rate of 4 mL/sec. CT venography was combined with thoracic CT angiography in 178 patients over 40 years of age. CT studies were interpreted first in the emergency setting and subsequently by two experienced chest radiologists. Untreated patients with normal results were contacted by telephone after 3 months. Proportions were compared with the chi(2) test, and agreement was assessed by calculating the kappa statistic (for thoracic CT angiography). RESULTS: Concordance between the two reading sessions was good (kappa = 0.88; 95% confidence interval: 0.77, 0.98). The proportion of nondiagnostic thoracic CT angiography studies was 9% (20 of 220). PE was found in 54 (24.5%) of 220 cases; eight (15%) of 54 patients had only subsegmental PE, which was associated with a calf vein thrombosis in two patients, and six patients (11%) had chronic PE. CT venography demonstrated venous thrombosis in 15% (26 of 178) of the patients thus studied, as well as in 45% (21 of 47) of patients with positive results at thoracic CT angiography and 4% (five of 131) of patients with negative results at thoracic CT angiography. The 3-month rate of thromboembolic events after negative results was 1.8% (two of 111) (95% confidence interval: 0.2%, 6.4%). CONCLUSION: Multi-detector row CT enables diagnosis in 91% of cases and identification of isolated subsegmental or chronic PE in a relatively high proportion of patients.

Adult↗

Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent.

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.

Animals↗

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Animals↗

Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable?

PURPOSE: To evaluate the intra- and interreader agreement of two-dimensional computed tomographic (CT) measurements of pulmonary nodules less than 2 cm in diameter. MATERIALS AND METHODS: Three readers independently made three serial measurements of each of 54 pulmonary nodules measuring 3-18 mm that had been observed on standard-dose multisection CT images obtained in 24 patients who ranged in age from 36 to 81 years (mean age, 54.6 years). There were 14 women (58%), who ranged in age from 43 to 81 years (mean age, 58.9 years), and 10 men (42%), who ranged in age from 36 to 65 years (mean age, 48.5 years). The largest transverse cross-sectional diameter of each nodule was measured at picture archiving and communication system, or PACS, workstations by using high-spatial-resolution reconstructed CT images and identical window settings. Intra- and interreader agreement were determined by using methods described by Bland and Altman: the coefficient of repeatability for intrareader agreement, and methods derived from the 95% limits of agreement defined by Bland and Altman for interreader agreement. RESULTS: The repeatability coefficients were 1.70, 1.32, and 1.51 mm for readers 1, 2, and 3, respectively. The 95% limits of agreement for the difference among readers were -1.73 and 1.73. CONCLUSION: Two-dimensional CT measurements are not reliable in the evaluation of small noncalcified pulmonary nodules.

Adult↗

Pulmonary nodules: preliminary experience with three-dimensional evaluation.

PURPOSE: To evaluate software designed to calculate pulmonary nodule volume in three dimensions. MATERIALS AND METHODS: Fifty-four solid noncalcified pulmonary nodules measuring 5-18 mm in diameter were studied with computed tomographic (CT) volumetric software. Baseline CT examinations were performed for various indications by using four-detector row multisection CT units, 1.25- or 2.50-mm sections, and a standard reconstruction algorithm. The percentage of successful nodule segmentations, as well as intraobserver variability, interreader agreement, and global repeatability of calculated volumes, was determined on the basis of consecutive measurements performed three times by three different radiologists by using the Bland and Altman method. The software was used to calculate the doubling time of 22 nodules for which a final diagnosis and comparable CT scans were available. RESULTS: Fifty-two (96%) of the 54 nodules were successfully segmented, allowing their volume to be calculated. Repeatability was high: There was no variation in the nine measurements of 35 (67%) of the 52 nodules. The coefficient of variation for the remaining 17 nodules (33%) was 2.26%. Bland and Altman 95% limits of acceptability, calculated on the basis of log-transformed data, yielded a maximum software measurement error of 6.38% of the previous volume measurement. Doubling time ranged from 4 to 188 years for the 13 benign nodules and from 37 to 216 days for the nine malignant nodules. CONCLUSION: Software volumetric analysis yielded repeatable estimates for 96% of the nodules examined. All software-calculated doubling times were in keeping with the benign or malignant nature of the nodules.

Adult↗

[Spiral CT: is it time for lung cancer screening?].

Recent studies have benefited from the progress of the scanner in order to relaunch the debate on the opportunity of screening lung cancer. Even if these initial studies have succeeded in showing that the practise of helical scan allows the screening of a considerable proportion of cases at an early stage which may have 5-year survivals of up to 70%, there is no specific indication of the diminution of lung cancer-specific mortality. Studies of cohorts of several dozen millions subjects during a period of 8 to 10 years are to be realised and an international pool will be charged of the harmonization of the protocols in order to realize the analyse of the collected information. An experimental study of 1000 subjects financed by a grant have started recently in France.

Aged↗

Can CT replace bronchoscopy in the detection of the site and cause of bleeding in patients with large or massive hemoptysis?

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Adult↗

Distribution of injected MRI contrast agents in mouse livers studied by confocal and SIMS microscopy.

OBJECTIVE: To localize magnetic resonance imaging (MRI) contrast agents injected intravenously into mouse livers. STUDY DESIGN: Parallel studies were performed on fluorescent europium and nonfluorescent, paramagnetic gadolinium and on a product combining nanoparticles of Fe and Texas Red to obtain combined information on the distribution of these molecules inside the liver. The distribution of different superparamagnetic iron oxides was also studied because the size of these new compounds is not always convenientfor microcirculation studies. RESULTS: Europium and Texas Red can be detected by confocal microscopy. Europium, iron and gadolinium can be detected by secondary ion mass spectrometry (SIMS) microscopy. Studies confirmed the complementarity of both microscopies. They also confirmed the possibility of using europium as a model of gadolinium to analyze thefate of MRI contrast agents. CONCLUSION: The methodology can be used on mice injected intravenously and analyzed by confocal and SIMS microscopy to localize MRI contrast agents inside cellular and tissue specimens of mice.

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