Multiple trauma in pregnant women: injury assessment, fetal radiation exposure and mortality. A multicentre observational study.

BACKGROUND: Fetal radiation exposure in pregnant women with trauma is a concern. The purpose of this study was to evaluate fetal radiation exposure with regard to the type of injury assessment performed. METHODS: It is a multicentre observational study. The cohort study included all pregnant women suspected of severe traumatic injury in the participating centres of a national trauma research network. The primary outcome was the cumulative radiation dose (mGy) received by the fetus with respect to the type of injury assessment initiated by the physician in charge of the pregnant patient. Secondary outcomes were maternal and fetal morbi-mortality, the incidence of haemorrhagic shock and the physicians' imaging assessment with consideration of their medical specialty. RESULTS: Fifty-four pregnant women were admitted for potential major trauma between September 2011 and December 2019 in the 21 participating centres. The median gestational age was 22 weeks [12-30]. 78% of women (n = 42) underwent WBCT. The remaining patients underwent radiographs, ultrasound or selective CT scans based on clinical examination. The median fetal radiation doses were 38 mGy [23-63] and 0 mGy [0-1]. Maternal mortality (6%) was lower than fetal mortality (17%). Two women (out of 3 maternal deaths) and 7 fetuses (out of 9 fetal deaths) died within the first 24 h following trauma. CONCLUSIONS: Immediate WBCT for initial injury assessment in pregnant women with trauma was associated with a fetal radiation dose below the 100 mGy threshold. Among the selected population with either a stable status with a moderate and nonthreatening injury pattern or isolated penetrating trauma, a selective strategy seemed safe in experienced centres.

Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MRI in patients with chronic liver disease.

The purpose of the present study was to develop and perform initial validation of dynamic MRI enhanced with gadoxetic acid as hepatobiliary contrast agent to quantify hepatic perfusion and hepatocyte function in patients with chronic liver disease. Free-breathing, dynamic gadoxetic acid-enhanced MRI was performed at 3.0 T using a 3D time-resolved angiography sequence with stochastic trajectories during 38 min. A dual-input three-compartment model was developed to derive hepatic perfusion and hepatocyte function parameters. Method feasibility was assessed in 23 patients with biopsy-proven chronic liver disease. Parameter analysis could be performed in 21 patients (91%). The hepatocyte function parameters were more discriminant than the perfusion parameters to differentiate between patients with minimal fibrosis (METAVIR F0-F1), intermediate fibrosis (F2-F3) and cirrhosis (F4). The areas under the receiver operating characteristic curves (ROCs) to diagnose significant fibrosis (METAVIR F ≥ 2) were: 0.95 (95% CI: 0.87-1; P<0.001) for biliary efflux, 0.88 (95% CI: 0.73-1; P<0.01) for sinusoidal backflux, 0.81 (95% CI: 0.61-1; P<0.05) for hepatocyte uptake fraction and 0.75 (95% CI: 0.54-1; P<0.05) for hepatic perfusion index (HPI), respectively. These initial results in patients with chronic liver diseases show that simultaneous quantification of hepatic perfusion and hepatocyte function is feasible with free breathing dynamic gadoxetic acid-enhanced MRI. Hepatocyte function parameters may be relevant to assess liver fibrosis severity.

Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis.

OBJECTIVES: Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. METHODS: Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. RESULTS: In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). CONCLUSION: These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. KEY POINTS: • Expression of hepatocyte transporters is modified in rats with advanced liver fibrosis. • Kinetic parameters at gadoxetate-enhanced MRI are correlated with hepatocyte transporter expression. • Hepatocyte transport function can be assessed with compartmental analysis of gadoxetate-enhanced MRI. • Compartmental analysis of gadoxetate-enhanced MRI might provide biomarkers in advanced liver fibrosis.

Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes.

BACKGROUND AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) is a commercialised hepatobiliary contrast agent used during liver magnetic resonance imaging (MRI) to detect liver diseases. It enters into human hepatocytes through organic anion transporting polypeptides (OATP1B1/B3) and crosses the canalicular transporter multiple resistance-associated protein 2 (MRP2) to be excreted into bile canaliculi. Gd-BOPTA can return to sinusoids via the sinusoidal transporters MRP3/MRP4. Hepatocyte concentrations of Gd-BOPTA depend on three clearances: the sinusoidal clearance or volume of sinusoidal blood cleared of drugs per unit of time and two hepatocyte clearances (into bile canaliculi or back to sinusoids) or volume of hepatocytes cleared of drugs per unit of time in the respective liver compartments. The present study investigates whether changing liver blood flow modifies hepatocyte concentrations when plasma concentrations do not change. METHODS: We perfused normal rat livers at various portal flow rates (24, 30, and 36 ml/min) with 200 µM Gd-BOPTA and measured sinusoidal clearances, hepatocyte clearances, and hepatocyte concentrations of Gd-BOPTA. RESULTS: We showed that varying portal flow rates changes the sinusoidal clearance of Gd-BOPTA despite its low extraction ratio. Portal flow rates do not modify Gd-BOPTA clearance from hepatocytes into bile canaliculi but can change hepatocyte clearance back to sinusoids. CONCLUSION: At a given perfused concentration, portal flow rates modify Gd-BOPTA hepatocyte concentrations, a result important to consider when interpreting liver imaging.

New imaging techniques for liver diseases.

Newly developed or advanced methods of ultrasonography and MR imaging provide combined anatomical and quantitative functional information about diffuse and focal liver diseases. Ultrasound elastography has a central role for staging liver fibrosis and an increasing role in grading portal hypertension; dynamic contrast-enhanced ultrasonography may improve tumor characterization. In clinical practice, MR imaging examinations currently include diffusion-weighted and dynamic MR imaging, enhanced with extracellular or hepatobiliary contrast agents. Moreover, quantitative parameters obtained with diffusion-weighted MR imaging, dynamic contrast-enhanced MR imaging and MR elastography have the potential to characterize further diffuse and focal liver diseases, by adding information about tissue cellularity, perfusion, hepatocyte transport function and visco-elasticity. The multiparametric capability of ultrasonography and more markedly of MR imaging gives the opportunity for high diagnostic performance by combining imaging biomarkers. However, image acquisition and post-processing methods should be further standardized and validated in multicenter trials.

Advanced fibrosis: Correlation between pharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver.

PURPOSE: To compare the value of enhancement and pharmacokinetic parameters measured at dynamic gadoxetate-enhanced magnetic resonance (MR) imaging in determining hepatic organic anion transporter expression in control rats and rats with advanced liver fibrosis. MATERIALS AND METHODS: Institutional animal review board approval was received before the study began. Advanced liver fibrosis was created in rats by means of carbon tetrachloride injections over an 8-week period. In 17 rats with liver fibrosis and eight control rats, dynamic gadoxetate-enhanced MR images of the liver were obtained during 1 hour after injection of 0.025 mmol gadoxetate per kilogram of body weight. Enhancement parameters (maximum enhancement [Emax], time to peak [Tmax], and elimination half-life) were measured on enhancement-versus-time curves, and pharmacokinetic parameters (hepatic extraction fraction [HEF] and mean residence time [MRT]) were obtained by means of deconvolution analysis of the concentration-versus-time curves in the liver and the portal vein. The parameters were correlated at simple and multiple regression analysis with the expression of the hepatic anion uptake transporter organic anion-transporting polypeptide 1A1 (Oatp1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 (Mrp2), and the backflux transporter Mrp4, as determined with reverse transcription polymerase chain reaction. RESULTS: In rats with advanced liver fibrosis, the Emax, Tmax, HEF, and MRT decreased significantly relative to those in control rats, whereas the elimination half-life increased significantly. The enhancement and pharmacokinetic parameters correlated significantly with the expression of the transporters at simple regression analysis. At multiple regression analysis, HEF was the only parameter that was significantly associated with the expression of Oatp1a1 and Mrp2 (P < .001, r = 0.74 and P < .001, r = 0.70, respectively). CONCLUSION: The pharmacokinetic parameter HEF at dynamic gadoxetate-enhanced MR imaging is independently correlated with hepatic organic anion transporter expression.

Determination of malignancy and characterization of hepatic tumor type with diffusion-weighted magnetic resonance imaging: comparison of apparent diffusion coefficient and intravoxel incoherent motion-derived measurements.

OBJECTIVE: The objective of this study was to compare the value of the apparent diffusion coefficient (ADC) determined with 3 b values and the intravoxel incoherent motion (IVIM)-derived parameters in the determination of malignancy and characterization of hepatic tumor type. MATERIALS AND METHODS: Seventy-six patients with 86 solid hepatic lesions, including 8 hemangiomas, 20 lesions of focal nodular hyperplasia, 9 adenomas, 30 hepatocellular carcinomas, 13 metastases, and 6 cholangiocarcinomas, were assessed in this prospective study. Diffusion-weighted images were acquired with 11 b values to measure the ADCs (with b = 0, 150, and 500 s/mm) and the IVIM-derived parameters, namely, the pure diffusion coefficient and the perfusion-related diffusion fraction and coefficient. The diffusion parameters were compared between benign and malignant tumors and between tumor types, and their diagnostic value in identifying tumor malignancy was assessed. RESULTS: The apparent and pure diffusion coefficients were significantly higher in benign than in malignant tumors (benign: 2.32 [0.87] × 10 mm/s and 1.42 [0.37] × 10 mm/s vs malignant: 1.64 [0.51] × 10 mm/s and 1.14 [0.28] × 10 mm/s, respectively; P < 0.0001 and P = 0.0005), whereas the perfusion-related diffusion parameters did not differ significantly between the 2 groups. The apparent and pure diffusion coefficients provided similar accuracy in assessing tumor malignancy (areas under the receiver operating characteristic curve of 0.770 and 0.723, respectively). In the multigroup analysis, the ADC was found to be significantly higher in hemangiomas than in hepatocellular carcinomas, metastases, and cholangiocarcinomas. In the same manner, it was higher in lesions of focal nodular hyperplasia than in metastases and cholangiocarcinomas. However, the pure diffusion coefficient was significantly higher only in hemangiomas versus hepatocellular and cholangiocellular carcinomas. CONCLUSIONS: Compared with the ADC, the diffusion parameters derived from the IVIM model did not improve the determination of malignancy and characterization of hepatic tumor type.

Fat deposition decreases diffusion parameters at MRI: a study in phantoms and patients with liver steatosis.

PURPOSE: Assess the effect of fat deposition on the MRI diffusion coefficients in lipid emulsion-based phantoms and patients with proven isolated liver steatosis. MATERIALS AND METHODS: Diffusion-weighted MRI with 11 b values from 0-500 s/mm(2) was performed in phantoms (fat fractions 0-18 %) with and without fat suppression and in 19 patients with normal liver (n = 14) or isolated liver steatosis (n = 5) proven by histopathology. The apparent, pure and perfusion-related diffusion coefficients and the perfusion fraction were measured. Spearman correlation coefficient and Mann-Whitney U test were used for comparisons. RESULTS: A strong correlation between the apparent and pure diffusion coefficients and fat fractions was seen in phantoms. The pure diffusion coefficient decreased significantly in patients with liver steatosis (0.96 ± 0.16 × 10(-3) mm(2)/s versus 1.18 ± 0.09 × 10(-3) mm(2)/s in normal liver, P = 0.005), whereas the decrease in apparent diffusion coefficient did not reach statistical significance (1.26 ± 0.25 × 10(-3) mm(2)/s versus 1.41 ± 0.14 × 10(-3) mm(2)/s in normal liver, P = 0.298). CONCLUSIONS: Fat deposition decreases the apparent and pure diffusion coefficients in lipid emulsion-based phantoms and patients with isolated liver steatosis proven by histopathology.

Diffusion-weighted MR imaging for the regional characterization of liver tumors.

PURPOSE: To determine if diffusion-weighted (DW) magnetic resonance (MR) imaging with measurements of the apparent diffusion coefficient (ADC), pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction can be used to differentiate between viable tumor and fibrous and necrotic regions within malignant liver tumors. MATERIAL AND METHODS: The prospective study was approved by the institutional review board, and informed consent was obtained from all patients. Forty-eight patients with 51 malignant tumors were assessed. MR images of the liver were obtained by using DW imaging with 11 b factors (0-500 sec/mm(2)) and gadolinium-enhanced three-dimensional gradient-echo T1-weighted imaging. Tumors were segmented into viable tumor and fibrous and necrotic regions according to the enhancement pattern after injection of a nonspecific gadolinium chelate and, in surgically removed lesions, results of histopathologic correlation. The ADC, pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction were calculated, and values were compared between viable tumor and fibrous and necrotic regions with the Kruskal-Wallis test followed by the Dunn multiple comparison test. RESULTS: The pure diffusion coefficient differed significantly between regions of viable tumor tissue and fibrosis (1.16 × 10(-3) mm(2)/sec ± 0.29 and 1.48 × 10(-3) mm(2)/sec ± 0.31, respectively; P = .016) and between regions of viable tumor tissue and necrosis (1.70 × 10(-3) mm(2)/sec ± 0.49, P = .002). There was a significantly lower perfusion fraction in necrotic regions (14% ± 6) than in viable tumor regions (21% ± 8, P = .005), but the perfusion fraction of the fibrous regions (21% ± 7) did not differ significantly from that of the other two regions. ADCs and perfusion-related diffusion coefficients did not differ significantly among the three regions. CONCLUSION: Results of this study show that viable tumor regions in malignant liver tumors can be differentiated from fibrous and necrotic regions with use of the pure diffusion coefficient but not with the other diffusion parameters.

MR elastography of liver tumours: value of viscoelastic properties for tumour characterisation.

OBJECTIVES: To assess the value of the viscoelastic parameters in the characterisation of liver tumours at MR elastography. PATIENTS AND METHODS: Ninety-four patients with liver tumours >1 cm prospectively underwent MR elastography using 50-Hz mechanical waves and a full three-directional motion-sensitive sequence. The model-free viscoelastic parameters (the complex shear modulus and its real and imaginary parts, i.e. the storage and loss moduli) were calculated in 72 lesions after exclusion of cystic, treated or histopathologically undetermined tumours. RESULTS: We observed higher absolute shear modulus and loss modulus in malignant versus benign tumours (3.38 ± 0.26 versus 2.41 ± 0.15 kPa, P < 0.01 and 2.25 ± 0.26 versus 1.05 ± 0.13 kPa, P < 0.001, respectively). Moreover, the loss modulus of hepatocellular carcinomas was significantly higher than in benign hepatocellular tumours. The storage modulus did not differ significantly between malignant and benign tumours. The area under the receiver-operating characteristic curve of loss modulus was significantly larger than that of the absolute shear modulus and storage modulus when comparing malignant and benign lesions. CONCLUSIONS: The increased loss modulus is a better discriminator between benign and malignant tumours than the increased storage modulus or absolute value of the shear modulus. KEY POINTS : • Magnetic Resonance elastography is a new method of assessing the liver. • Increased loss modulus is an indicator of malignancy in hepatic tumours. • Loss modulus is a better discriminator than absolute shear modulus values. • The viscoelastic properties of lesions offer promise for characterising liver tumours.

In vivo labelling of resting monocytes in the reticuloendothelial system with fluorescent iron oxide nanoparticles prior to injury reveals that they are mobilized to infarcted myocardium.

AIMS: To evaluate the feasibility of loading resting monocytes/macrophages by intravenous (i.v.) injection of fluorescent iron oxide nanoparticles prior to injury and tracking of these cells in the very same animal to myocardial infarction (MI) by magnetic resonance imaging (MRI) and optical imaging. METHODS AND RESULTS: Rats were injected with fluorescent iron oxide nanoparticles (10 mg/kg) (n = 15) prior to injury. After disappearance of the nanoparticles from the blood, MI was induced. Monocytes/macrophages were then tracked in the very same animal by MRI and optical imaging. Control groups were (i) non-injected animals (n = 15), (ii) injected animals associated with a sham operation (n = 8), and (iii) animals treated with an anti-inflammatory agent (n = 6). The presence of iron-loaded cells can be detected by MRI in vivo in the infarcted myocardium. Here, we showed that the detection of inflammatory cells in vivo correlated well with ex vivo imaging (MRI and reflectance fluorescence) and histology. We also showed that the method is robust enough to depict changes in the inflammatory response. CONCLUSION: This study demonstrates that resting monocytes/macrophages can be loaded in vivo by a simple i.v. injection of fluorescent superparamagnetic iron oxide nanoparticles prior to injury and then tracked, in the same animal, in a model of ischaemia-reperfusion leading to myocardial infarct. Although previous studies of macrophages infiltration following MI have labelled the macrophages after injury, this study, for the first time, has pre-load the resting monocytes with fluorescent iron oxide nanoparticles.

Cine and tagged cardiovascular magnetic resonance imaging in normal rat at 1.5 T: a rest and stress study.

BACKGROUND: The purpose of this study was to measure regional contractile function in the normal rat using cardiac cine and tagged cardiovascular magnetic resonance (CMR) during incremental low doses of dobutamine and at rest. METHODS: Five rats were investigated for invasive left ventricle pressure measurements and five additional rats were imaged on a clinical 1.5 T MR system using a cine sequence (11-20 phases per cycle, 0.28/0.28/2 mm) and a C-SPAMM tag sequence (18-25 phases per cycle, 0.63/1.79/3 mm, tag spacing 1.25 mm). For each slice, wall thickening (WT) and circumferential strains (CS) were calculated at rest and at stress (2.5, 5 and 10 microg/min/kg of dobutamine). RESULTS: Good cine and tagged images were obtained in all the rats even at higher heart rate (300-440 bpm). Ejection fraction and left ventricular (LV) end-systolic volume showed significant changes after each dobutamine perfusion dose (p < 0.001). Tagged CMR had the capacity to resolve the CS transmural gradient and showed a significant increase of both WT and CS at stress compared to rest. Intra and interobserver study showed less variability for the tagged technique. In rats in which a LV catheter was placed, dobutamine produced a significant increase of heart rate, LV dP/dtmax and LV pressure significantly already at the lowest infusion dose. CONCLUSION: Robust cardiac cine and tagging CMR measurements can be obtained in the rat under incremental dobutamine stress using a clinical 1.5 T MR scanner.

High-resolution complementary spatial modulation of magnetization (CSPAMM) rat heart tagging on a 1.5 Tesla Clinical Magnetic Resonance System: a preliminary feasibility study.

The purpose of this study was to assess the feasibility of cardiac magnetic resonance (MR) tagging in rats on a standard clinical 1.5T MR system. Small animal models have been largely used as an experimental model in cardiovascular disease studies but mainly on high field systems (>4T) dedicated to research. Given the larger availability of routine clinical MR systems in centers with active cardiac research programs, it is of great interest to perform small animal imaging on whole-body MR systems of moderate field strength. The feasibility study was performed on 7 rats within 6 to 8 hours after myocardial infarction and 3 normal control rats. Myocardial strain was measured successfully in normal rats using the harmonic phase (ie, HARP) method, and a transmural gradient was demonstrated. In a rat model of acute occlusion/reperfusion, the myocardial circumferential strains were decreased, but the transmural strain gradient was preserved. This study demonstrated the feasibility of cardiac MR tagging in rats with a subendocardial resolution using a clinical 1.5T system.

Microstructural development of human brain assessed in utero by diffusion tensor imaging.

BACKGROUND: Diffusion-weighted MR imaging (DWI) has been shown to be a great tool to assess white matter development in normal infants. Comparison of cerebral diffusion properties between preterm infants and fetuses of corresponding ages should assist in determining the impact of premature ex utero life on brain maturation. OBJECTIVE: To assess in utero maturation-dependent microstructural changes of fetal cerebral white matter using diffusion tensor MR imaging. MATERIALS AND METHODS: An echoplanar sequence with diffusion gradient (b=700 s/mm(2)) applied in six non-colinear directions was performed between 31 and 37(+3) weeks of gestation in 24 fetuses without cerebral abnormality on T1- and T2-weighted images. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the white matter. RESULTS: Mean ADC values were 1.8 microm(2)/ms in the centrum semiovale, 1.2 microm(2)/ms in the splenium of the corpus callosum and 1.1 microm(2)/ms in the pyramidal tract. The paired Wilcoxon rank test showed significant differences in ADC between these three white matter regions. Mean FA values were 1.1%, 3.8% and 4.7%, respectively, in the centrum semiovale, corpus callosum and pyramidal tract. A significant age-related decrease in ADC and an increase in FA towards term were demonstrated in the pyramidal tract and corpus callosum. CONCLUSION: Diffusion tensor imaging in utero can provide a quantitative assessment of the microstructural development of fetal white matter. Anisotropic parameters of the diffusion tensor should improve with technical advances.

Patterns of excitotoxin-induced brain lesions in the newborn rabbit: a neuropathological and MRI correlation.

There is pressing need to employ new advances in structural MR brain imaging to better diagnose brain damage in newborn infants. Timely application of such technology will enable improved therapeutic interventions. Diffusion-weighted sequences are a sensitive marker of very early neuronal injury, the spatial pattern of which provides critical information regarding the underlying pathophysiology. We have modified our murine model of excitotoxic neonatal brain injury to the rabbit, an animal whose brain is larger and where the neuroanatomic organization of the subcortical white matter more closely resembles that of the human. Utilizing this rabbit model, we undertook an MRI/histopathologic correlation. We found that as with the mouse, there is a spatiotemporal selectivity to the pattern of brain injury, and that the period from postnatal day (P) 7 to P9 in rabbits corresponds to the time of maximum vulnerability of the brain to excitotoxic white matter damage, which neuropathologically simulates periventricular leukomalacia (PVL). We additionally noted that diffusion-weighted imaging provided the most sensitive means of detecting such lesions and that this method was sensitive to structural maturational changes accompanying the normal cortical ontogeny. Taken together, our findings suggest that this rabbit model of perinatal excitotoxic brain injury will be a valuable addition to experimental approaches to further our understanding of perinatal brain damage, that diffusion-weighted imaging will be an invaluable adjunct to the diagnosis of such injury, and that therapeutic strategies aimed at interrupting the evolution of PVL should include targeting the pathophysiologic cascade induced by excitotoxic neonatal brain injury.

Fetal brain MRI: segmentation and biometric analysis of the posterior fossa.

This paper presents a novel approach to fetal magnetic resonance image segmentation and biometric analysis of the posterior fossa's midline structures. We developed a semi-automatic segmentation method (based on a region growing technique) and tested the algorithm on images of 104 normal fetuses. Using the segmented regions of interest (posterior fossa, vermis, and brainstem), we computed four relative area ratios. Statistical and clinical analysis of our results showed that the relative development of these structures appears to be independent of pregnancy term. In an additional study of 23 pathological cases, one of the four measurements was always significantly different from the corresponding value observed in normal cases.

Gestational hypoxia induces white matter damage in neonatal rats: a new model of periventricular leukomalacia.

In the premature infant, periventricular leukomalacia, usually related to hypoxicischemic white matter damage, is the main cause of neurological impairment. We hypothesized that protracted prenatal hypoxia might induce white matter damage during the perinatal period. Pregnant Sprague-Dawley rats were placed in a chamber supplied with hypoxic gas (10% O2-90% N2) from embryonic day 5 (E5) to E20. Neonatal rat brains were investigated by histology, immunocytochemistry, western blotting, in situ hybridization, DNA fragmentation analysis, and in vivo magnetic resonance imaging (MRI). Body weight of pups subjected to prenatal hypoxia was 10 to 30% lower from P0 to P14 than in controls. Specific white matter cysts were detected between P0 and P7 in pups subjected to prenatal hypoxia, in addition to abnormal extra-cellular matrix, increased lipid peroxidation, white matter cell death detected by TUNEL, and increased activated macrophage counts in white matter. Subsequently, gliotic scars and delayed myelination primarily involving immature oligodendrocytes were seen. In vivo MRI with T1, T2, and diffusion sequences disclosed similar findings immediately after birth, showing strong correlations with histological abnormalities. We speculate that protracted prenatal hypoxia in rat induces white matter damage occurring through local inflammatory response and oxidative stress linked to re-oxygenation during the perinatal period.

Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients.

PURPOSE: To (a) evaluate liver diffusion isotropy, (b) compare two diffusion-weighted magnetic resonance (MR) imaging sequences for the characterization of focal hepatic lesions by using two or four b values, and (c) determine an apparent diffusion coefficient (ADC) threshold value to differentiate benign from malignant lesions. MATERIALS AND METHODS: Sixty-six patients were examined with two single-shot echo-planar diffusion-weighted MR sequences. In the first sequence, liver diffusion isotropy was evaluated by using diffusion gradients in three directions with two b values. In the second sequence, a unidirectional diffusion gradient was used with four b values. ADCs were measured in 43 patients with 52 focal hepatic lesions more than 1 cm in diameter and in 23 patients with 14 normal and nine cirrhotic livers and were compared by using nonparametric tests. RESULTS: Diffusion in the liver parenchyma was isotropic. ADCs of focal hepatic lesions were significantly different between sequences (P <.01). The mean (+/- SD) ADCs in the first sequence were 0.94 x 10(-3) mm(2)/sec +/- 0.60 for metastases, 1.33 x 10(-3) mm(2)/sec +/- 0.13 for HCCs, 1.75 x 10(-3) mm(2)/sec +/- 0.46 for benign hepatocellular lesions, 2.95 x 10(-3) mm(2)/sec +/- 0.67 for hemangiomas, and 3.63 x 10(-3) mm(2)/sec +/- 0.56 for cysts. There was a significant difference between benign (2.45 x 10(-3) mm(2)/sec +/- 0.96, isotropic value) and malignant (1.08 x 10(-3) mm(2)/sec +/- 0.50) lesions (P <.01 for both sequences). CONCLUSION: Diffusion-weighted MR imaging can help differentiate benign from malignant hepatic lesions. The use of two b values in one direction could be sufficient for the design of MR sequences in the liver.