T2 relaxation time as a marker of brain myelination: experimental MR study in two neonatal animal models.

The progress of myelination in the brain was evaluated by visualization of grey/white matter differentiation on magnetic resonance (MR) images and quantitative analysis of MR data. In vivo quantitative MR imaging was used to monitor the T2 transverse relaxation time changes associated with cerebral development and myelination. The progress of myelination was evaluated using two neonatal animal models, the monkey and the dog, known to mature at very different rates. Three beagles were studied from birth to 4 months of age and nine baboons from 1 to 30 months of age. The T2 values in the frontal, parietal and occipital white matter were calculated and the changes in these values with age were followed. Brain maturation in both species was found to correspond to decreasing T2 values in both grey and white matter. This decrease was observed both in the dog brain and, despite slower maturation, in the baboon brain, and appeared to fit with the myelination process in these models. Exploiting the physicochemical parameters of water in tissues via T2 determination is a convenient and reliable strategy for the documentation of brain development in both experimental approaches and clinical situations.

Quantitative MR renography using a calibrated internal signal (ERETIC).

To measure MR renograms, cortical and medullary kidney signal intensity evolution is followed after contrast agent injection. To obtain an accurate quantitative signal measurement, the use of a reference signal is necessary to correct the potential MRI system variations in time. The ERETIC method (Electronic Reference To access In vivo Concentrations) provides an electronic reference signal. It is synthesized as an amplitude modulated RF pulse applied during the acquisition. The ERETIC method was as precise as the external tube reference method but presents major advantages like its free adjustability (shape, location and magnitude) to the characteristics of the organ studied as well as its not taking room inside the magnet. Even though ERETIC showed a very good intrinsic stability, systems' variations still affect its signal in the same way as real NMR signals are affected. This method can be easily implemented on any imaging system with two RF channels.

MR assessment of the brain maturation during the perinatal period: quantitative T2 MR study in premature newborns.

The purpose of our study is to trace in vivo and during the perinatal period, the brain maturation process with exhaustive measures of the T2 relaxation time values. We also compared regional myelination progress with variations of the relaxation time values and of brain signal. T2 relaxation times were measured in 7 healthy premature newborns at the post-conceptional age of 37 weeks, using a Carr-Purcell-Meiboom-Gill sequence (echo time 60 to 150 ms), on a 2.35 Tesla Spectro-Imaging MR system. A total of 62 measures were defined for each subject within the brain stem, the basal ganglia and the hemispheric gray and white matter. The mean and standard deviation of the T2 values were calculated for each location. Regional T2 values changes and brain signal variations were studied. In comparison to the adult ones, the T2 relaxation time values of both gray and white matter were highly prolonged and a reversed ratio between gray and white matter was found. The maturational phenomena might be regionally correlated with a T2 value shortening. Significant T2 variations in the brainstem (p < 0.02), the mesencephalon (p < 0.05), the thalami (p < 0.01), the lentiform nuclei (p < 0.01) and the caudate nuclei (p < 0.02) were observed at an earlier time than they were visible on T2-weighted images. In the cerebral hemispheres, T2 values increased from the occipital white matter to parietal, temporal and frontal white matter (p < 0.05) and in the frontal and occipital areas from periventricular to subcortical white matter (p < 0.01). Maturational progress was earlier and better displayed with T2 measurements and T2 mapping. During the perinatal period, the measurements and analysis of T2 values revealed brain regional differences not discernible with T2-weighted images. It might be a more sensitive indicator for assessment of brain maturation.

A newborn piglet study of moderate hypoxic-ischemic brain injury by 1H-MRS and MRI.

Cerebral hypoxia-ischemia (HI) is an important cause of perinatal brain damage in the term newborn. The areas most affected are the parasagittal regions of the cerebral cortex and, in severe situations, the basal ganglia. The aim of this study was to show that the newborn piglet model can be used to produce neuropathology resulting from moderate HI insult and to monitor damage for 7 days. Two acute cerebral HI were induced in newborn Large White piglets by reducing the inspired oxygen fraction to 4% and occluding the carotid arteries. Newborn piglets were resuscitated, extubated and monitored for 7 days. (31)P magnetic resonance spectroscopy (MRS) offers the ability to monitor the severity of the HI insults. Lactate (Lac) was detected in the HI group at 2 h, 3 days and 5 days after insult by (1)H MRS. Lac/n-acetylaspartate and Lac/choline and Lac/creatine ratios increased significantly (p < 0.01) in the HI group 2 h after HI insults and remained high over 7 days. For the HI group, mean T(2) values increased significantly in the parietal white matter (subcortical) for 5 days after HI insult [117.5 (+/-7.4) to 158.5 (+/-19.2) at T+3 days, 167.7 (+/-15.4) at T+5 days and 160.9 (+/-10.1) at T+7 days (p < 0.01)]. This newborn piglet model of moderate HI brain injury with reproducible cerebral damage could be use as reference for the study of neuroprotective strategy for a period of 7 days.

[Nuclear magnetic resonance spectroscopy: methodology and applications to the study of asphyxia neonatorum]. / La spectroscopie par résonance magnétique nucléaire: méthodologie et applications à l'étude de l'asphyxie périnatale.

Cerebral metabolism has been extensively studied by magnetic resonance spectroscopy (MRS). MRS allows the study of neonates brain maturation as well as the onset and the evolution of brain injury. The use of phosphorous spectroscopy allows the quantification of phosphorylated metabolites. Thus, the measurement of the relative concentrations of creatine-phosphate and inorganic-phosphate is a prognostic factor of the outcome of a neonate after birth asphyxia. Absolute concentrations have more recently been studied and seem to be more significant. Proton MRS gives access to brain metabolites such as choline, lactate, N-acetyl aspartate and taurine. Its use is more recent than the phosphorous spectroscopy but first results already show its potential in neonatology.

D2 receptor imaging in neonates using I-123 iodobenzamide brain SPECT.

PURPOSE: Hypoxic-ischemic injury induces early changes in cerebral energy that later lead to the presence and extension of brain damage and subsequently to severe neurodevelopmental impairments such as the dyskinetic form of cerebral palsy, which is associated with damage to the striatum. The purpose of the current study was to evaluate the viability of D2 receptors in the perinatal period using I-123 iodobenzamide brain SPECT and to correlate this with early neurologic status. METHODS: After obtaining informed parental consent, 12 full-term neonates with hypoxic-ischemic events were included. I-123 iodobenzamide brain SPECT was performed 1 week after birth, corresponding to a gestational age of 39.2+/-1.7 weeks. Images were acquired using a brain-dedicated gamma camera 1 hour after intravenous injection of 30 MBq (0.8 mCi) I-123 iodobenzamide. Magnetic resonance images (T2 weighted sequence: repetition time/echo time: 2,000/30 to 150) of the brains of the same neonates were acquired on the same day. RESULTS: The right and left striatum:cerebellum activity ratios were between 1.28 and 2.25, with the greatest concentration of I-123 iodobenzamide occurring in the striatum area. A tendency of the striatum:cerebellum ratio to decrease was observed as the severity of the perinatal hypoxic-ischemic event increased despite striatal hypersignal on magnetic resonance imaging in only two neonates. CONCLUSIONS: This study, which confirms that I-123 iodobenzamide could be used in the neonatal period, shows the biochemical maturation of D2 receptors as early as 1 week after birth and also suggests the deleterious effect of perinatal hypoxic-ischemic events on D2 receptors.

[Circulation and cerebral metabolism in neonatal hypoxia-ischemia]. / Circulation et métabolisme cérébraux au cours de l'hypoxie-ischémie néonatale.

The basic physiological variable in hypoxic-ischaemic brain injury is cerebral oxygen delivery. When oxygen delivery becomes insufficient to meet the cellular demands for oxygen, a sequence of biochemical events will be triggered leading to cell death. High levels of CBF following severe birth asphyxia is now well documented by Doppler ultrasound which has been shown to be a useful prognostic indicator following birth asphyxia. Near infrared spectroscopy (NIRS) is of great potential value since it may be used at the bed-sid and allows to measure the cerebral blood volume and the concentrations of cytochrome aa3. Magnetic resonance spectroscopy (MRS) allows noninvasive assessment of cerebral metabolism in asphyxiated neonates. 31P MRS has demonstrated that birth asphyxia leads to delayed impairment of cerebral energy metabolism and is predictive of later neurodevelopmental outcome. 1H MRS has shown lactate accumulation and a later decline in N-acetyl aspartate concentration.

Concentration Measurement by Proton NMR Using the ERETIC Method.

The ERETIC method (Electronic REference To access In vivo Concentrations) provides a reference signal, synthesized by an electronic device, which can be used for the determination of absolute concentrations. The results presented here demonstrate the accuracy and precision of the method in the case of (1)H high resolution NMR. Five tubes were filled with D(2)O solutions of trimethylamine hydrochloride (TMA) 3.84 mM and sodium lactate at concentrations ranging from 5.25 to 54.11 mM. Results obtained with the ERETIC method were compared to those obtained by using TMA as an internal reference. The standard deviations were the same for the two methods and always lower than 1% of the mean. The accuracy (difference between true value and measured value) was slightly better for the ERETIC method than for the internal reference. No significant variation was observed when the experiments were performed over 56 h. Measurements were repeated once a month during three months. As the values obtained showed a standard deviation of only 3%, we can conclude that the ERETIC method has a good stability and only requires monthly calibration. Furthermore, it must be noted that nothing is added to the sample and that the reference signal frequency can be freely chosen to fall within a transparent region of the spectrum.

A new method for absolute quantitation of MRS metabolites.

A new method for absolute quantitation of MRS spectra is presented. This method is not based on a reference peak, derived from a real NMR signal, but rather on a synthesized NMR reference produced by an electronic device, transmitted by a broad-band antenna to avoid quality factor variations. This signal is therefore received at the same time as the sample signal. The reference line produced is stable in time (maximum variation lower than 2%) and allows precise and accurate measurement of absolute concentrations (mean error lower than 3%) in vitro and in vivo.

Follow-up of intracranial aneurysms treated with detachable coils: comparison of plain radiographs, 3D time-of-flight MRA and digital subtraction angiography.

All patients with aneurysms treated with Guglielmi detachable coils (GDC) are undergo angiography to assess long-term stability of aneurysm exclusion or to show recurrence of the aneurysm sac, which may require further treatment. We prospectively compared the plain-film appearance of the coil-mass, 3D time-of-flight MR angiography (TOF MRA) and digital subtraction angiography (DSA) for the detection of aneurysm recanalisation during follow-up. We studied 60 patients with 74 intracranial aneurysms treated with Guglielmi detachable coils. We used the unsubtracted image of the angiograms performed at the completion of any embolisation procedure and at follow-up as the plain radiographs. Recanalisation was considered if loosening, compaction or reorientation of the coil mass was apparent. TOF MRA was performed to assess the presence and size of a neck remnant. DSA was regarded as the definitive investigation. Comparison of the techniques showed good agreement as regards aneurysm recanalisation. MRA was more accurate than plain radiography and could replace DSA for long term follow- up. The initial follow-up examination should, however, include both modalities. In cases of contraindications or limitations to MRA, the interval between follow-up angiographic examinations could be increased if there is no change in the plain-film coil-mass appearances.