Mikael Mosskin

Spontaneous brain activity in the newborn brain during natural sleep--an fMRI study in infants born at full term.

Recent progress in functional neuroimaging research has provided the opportunity to probe at the brains intrinsic functional architecture. Synchronized spontaneous neuronal activity is present in the form of resting-state networks in the brain even in the absence of external stimuli. The objective of this study was to investigate the presence of resting-state networks in the unsedated infant brain born at full term. Using functional MRI, we investigated spontaneous low-frequency signal fluctuations in 19 healthy full-term infants. Resting-state functional MRI data acquired during natural sleep was analyzed using independent component analysis. We found five resting-state networks in the unsedated infant brain born at full term, encompassing sensory cortices, parietal and temporal areas, and the prefrontal cortex. In addition, we found evidence for a resting-state network that enclosed the bilateral basal ganglia.

Positron Emission Tomography Compared with Magnetic Resonance Imaging and Computed Tomography in Supratentorial Gliomas using Multiple Stereotactic Biopsies as Reference

Ten patients with findings at computed tomography (CT) suggesting intracranial supratentorial glioma were investigated to compare the diagnostic efficacy of this technique with that of positron emission tomography (PET) using 11C-methionine and exminations with magnetic resonance (MR). The findings were related to histopathologic examination of serial stereotactic biopsies, which were guided by the appearance of the lesions on PET examination. To obtain corresponding slice orientation with the different examination techniques, an individually shaped helmet fixation was used. However, in 3 cases this fixation device could not be used for MR. Histopathologic diagnosis, obtained in all cases from multiple target stereotactic biopsies, included glioma in 9 patients and reactive gliosis in one case. A detailed comparison of the three imaging techniques and the findings at stereotactic biopsies was possible in 7 patients, while in 3 patients comparison with MR was less exact due to the patients refusal to wear the helmet during this examination. MR was the most accurate method for outlining the total extent of a lesion, i.e. the tumor and the edema surrounding it. Four lesions had homogeneous signal characteristics and in 6 lesions two (or more) compartments could be distinguished with MR. In 5 cases the MR findings were in complete agreement with the histopathologic findings. However, a thorough correlation between signal characteristics and histology was not possible. Using PET the occurrence and the extent of tumor tissue was correctly predicted in 7 patients. The PET was normal in one case. Findings at CT were in agreement with the histopathologic diagnosis in 5 patients. MR was the most sensitive method for the detection of lesions. PET using methionine appeared to have a somewhat higher capacity to outline correctly the true extent of a tumor. The combination of CT and PET was superior to MR for determining the type and grade of the tumors.

Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors.

Sixteen patients with supratentorial tumors were examined with positron emission tomography (PET) using [( 11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA as well as CT. There were nine astrocytomas (grade II), three oligoastrocytomas (grade II), two anaplastic astrocytomas (grade III), and two meningiomas. Six patients with low-grade astrocytomas and all three patients with oligoastrocytomas had an accumulation of [11C]methionine varying from slightly to intensely increased as compared with normal brain tissue. There was a markedly increased uptake of methionine in the anaplastic astrocytomas. Three of the low-grade astrocytomas had a decreased uptake of [11C]methionine in at least part of the tumor as compared with normal brain tissue. Contrast enhancement on CT or uptake of [68Ga]EDTA was not a prerequisite for increased accumulation of methionine. Uptake of [11C]glucose was lower than or equal to that of normal brain tissue in the low-grade tumors and also in one of the two anaplastic astrocytomas and in the bulk of the other. In each individual case the methionine uptake tended to be higher--or less decreased--than the glucose uptake. In the low-grade tumors the uptake of methionine and that of glucose were often different, occasionally markedly different, as far as the tumoral-peritumoral areas involved. These differences were even more remarkable in the two anaplastic astrocytomas. An increased uptake of methionine was often seen in areas appearing normal on CT. It appears that PET with [11C]glucose has limitations with regard to delineation of the low-grade astrocytomas, whereas PET with [11C]methionine usually better reflects the extent of these tumors and, to a lesser degree, the extent of the high-grade neoplasms. The results of PET with [68Ga]EDTA were similar to those with postcontrast CT in most patients. The two meningiomas exhibited a high uptake of all tracers used for PET as well as a marked contrast enhancement on CT. The extent of the meningiomas judged by PET with the various tracers correlated well with the extent assessed by postcontrast CT.

Positron emission tomography with 11C-methionine and computed tomography of intracranial tumours compared with histopathologic examination of multiple biopsies.

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using 11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.

Pet Study of Methionine Accumulation in Glioma and Normal Brain Tissue: Competition with Branched Chain Amino Acids

Five patients with glioma were examined with positron emission tomography using ([11C]methyl)-L-methionine. The study was repeated while the patient was being infused with branched chain amino acids (BCAA), 250 μmol/min. The accumulation rates of methionine in tumor tissue and in normal brain tissue were compared without and with the infusion of amino acids. Both tumor tissue and normal brain tissue showed a reduction in the methionine accumulation by 35% while the patient received the infusion. In one patient with a severe blood-tissue barrier disruption the tumor accumulation rate was unaffected. It is concluded that in gliomas without severe blood-tissue barrier disruption, the accumulation of methionine is governed by processes exhibiting similar properties regarding competition with BCAA as in normal brain tissue.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants

OBJECTIVE To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study

Aim:  To investigate cerebral white matter (WM) abnormalities (J Pediatr 2003; 143: 171) and diffuse and excessive high signal intensities (DEHSI), (J Pediatr 1999; 135: 351) in a cohort of extremely preterm infants born in Stockholm during a 3‐year period, using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI study

Aims: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors.

Cranial ultrasound and MRI at term age in extremely preterm infants

Objectives Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. Methods In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. Results Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. Conclusions All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.

Congenital cytomegalovirus infection: the impact of cerebral cortical malformations

Aim:  Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging.