The cerebellar development in chinese children-a study by voxel-based volume measurement of reconstructed 3D MRI scan

Cerebellar disorder was frequently reported to have relation with structural brain volume alteration and/or morphology change. In dealing with such clinical situations, we need a convenient and noninvasive imaging tool to provide clinicians with a means of tracing developmental changes in the cerebellum. Herein, we present a new daily practice method for cerebellum imaging that uses a work station and a software program to process reconstructed 3D neuroimages after MRI scanning. In a 3-y period, 3D neuroimages reconstructed from MRI scans of 50 children aged 0.2-12.7 y were taken. The resulting images were then statistically analyzed against a growth curve. We observed a remarkable increase in the size of the cerebellum in the first 2 y of life. Furthermore, the unmyelinated cerebellum grew mainly between birth and 2 y of age in the postnatal stage. In contrast, the postnatal development of the brain mainly depended on the growth of myelinated cerebellum from birth through adolescence. This study presents basic data from a study of ethnic Chinese children's cerebellums using reconstructed 3D brain images. Based on the technique we introduce here, clinicians can evaluate the growth of the brain.     

Liver, meconium, haemorrhage: the value of T1-weighted images in fetal MRI

Background Ultrafast T2-weighted (T2-W) MRI sequences are currently considered a routine technique for fetal MR imaging. Limited experience exists with fetal T1-weighted (T1-W) imaging techniques.Objective To determine MRI patterns of some fetal abdominal or haemorrhagic disorders with particular respect to the diagnostic value of T1-W images.Materials and methods In addition to standard T2-W single-shot sequences, T1-W single-shot and/or multislice sequences were employed in 25 MR examinations performed in 23 fetuses between 20 and 36 weeks of gestation for more detailed assessment of liver, meconium-filled digestive tract, haemorrhage, or further characterization of a fetal abdominal mass. Diagnostic value and presence of motion artefacts on T1-W images was recorded in each case.Results T1-W images enabled superior delineation of fetal liver and large intestine. They provided additional diagnostic information in 9 (39%) of 23 fetuses. One false-positive and one false-negative MRI diagnosis of malrotation anomaly were encountered. Use of single-shot T1-W sequences reduced the occurrence of motion artefacts in 64%.Conclusion Our results suggest that the specific signal properties of methaemoglobin, meconium and liver are sufficiently important for T1-W sequences to become a routine part of fetal MRI protocols when dealing with digestive tract anomalies, diaphragmatic and abdominal wall defects, intraabdominal masses, and fetal haemorrhage.     

New advances in fetal MR neuroimaging

MR is now routinely and widely used in fetal neuroimaging and has proven to be valuable in the detection of many cerebral lesions, either genetically determined or acquired in utero. However, its efficiency has certain limits in the detection of diffuse white-matter abnormalities, the evaluation of fibre development and the demonstration of metabolic disorders. Moreover, conventional fetal MR imaging provides only a morphological approach to the fetal brain. New techniques such as diffusion-weighted imaging, diffusion tensor imaging, proton MR spectroscopy and functional MR imaging are developing. The majority of these are not used routinely. The principles, aims, technical problems and possible applications of these techniques for imaging the fetus are discussed.     

Visualization of Intracranial Structures in Early Human Embryos using 3-D Computer Graphics Technique

In classic human embryology, one of the most important techniques to observe embryonic structures three-dimensionally (3-D) was to reconstruct embryos or their parts using wax plate models from serial histological sections. However, wax plate reconstruction does not allow observation of internal structures and lumens unless the models are cut after reconstruction. The development of computer graphics has enabled us to reconstruct various biologic structures on the viewing screen and to manipulate the computer images as freely as we desire. Nevertheless, until now computer reconstruction has not been used frequently to study human organogenesis. We reviewed and photographed serial histological sections of early human embryos, projected these photographed slides onto a screen and traced the outlines of specific structures under study on a digitizing pad that was interfaced with a 16 bit computer. The digitized images were combined using a software for 3-D reconstruction. With this technique, we were able to visualize the anatomical localization and interrelation of various structures inside the human head during the embryonic period. The 3-D reconstruction technique should be of potential use for the study of normal and abnormal morphogenesis.     

Blechschmidt Collection: Revisiting specimens from a historical collection of serially sectioned human embryos and fetuses using modern imaging techniques

Along with the Carnegie Collection in the United States and the Kyoto Collection in Japan, the Blechschmidt Collection (Georg‐August‐University of Göttingen, Germany) is a major historical human embryo and fetus collection. These collections are of enormous value to human embryology; however, due to the nature of the historical histological specimens, some stains are fading in color, and some glass slides are deteriorating over time. To protect these specimens against such degradation and ensure their future usefulness, we tried to apply modern image scanning and computational reconstruction. Samples of histological specimens of the Blechschmidt Collection were digitized into images using commercial flatbed scanners with a resolution of 4800 pixels per inch. Two specimens were reconstructed into three‐dimensional (3D) images by using modern techniques to vertically stack two‐dimensional images of the slices into 3D blocks. The larger specimen of crown‐rump length (CRL) 64.0 mm, a series of very large histological sections in human embryology, was reconstructed clearly, with its central nervous system segmented before stacking. The smaller specimen of CRL 17.5 mm was also reconstructed into 3D images. The outer surface of the embryo was intact, and its development was classified according to the widely used Carnegie stages (CSs). The CS of the specimen was identified as the later half of CS 20. The invaluable Blechschmidt Collection can be revisited for further research with modern techniques such as digital image scanning and computational 3D reconstruction.     

Age-related changes of the MR appearance of CNS involvement in neurocutaneous melanosis complex

We report a case of giant congenital melanocytic nevi (GCMN) at risk of developing neurocutaneous melanosis (NCM) with age-related changes observable on MRI of the brain. However, although the usefulness of MR imaging in NCM is well known, age-related changes on MRI have rarely been reported. The prevalence of positive MRI findings and prognosis in GCMN accompanied by epilepsy and/or mental retardation awaits clarification. This case report may suggest the importance of serial brain MRI in cases of GCMN in assessing the risk of NCM. Received: 22 April 1999/Accepted 20 March 2000     

MRI of fetal and neonatal cerebellar development

In the last few years magnetic resonance imaging (MRI) has expanded its diagnostic capability in the evaluation of fetal brain. Starting from the 18th to 20th gestational weeks, MRI can reliably depict fetal brain anatomy and locate pathology, offering a robust and reliable tool for the assessment of disorders of the fetal central nervous system. In this review quantitative and qualitative in vivo MRI data on fetal cerebellar development are presented. Our normative reference data have been obtained from a database of 580 MR fetal imaging studies. Normal cases were selected within normal MRI fetal brain studies, and all selected cases had a normal clinical evaluation and a normal cranial ultrasound or MR image after birth. Fetal cerebellar development is gradual, steady, and grossly comparable to the development of the supratentorial brain. Archicerebellar (flocculonodular lobe) and paleocerebellar (vermis) structures develop before the neocerebellum (cerebellar hemispheres) that develops more slowly and largely after birth.     

MRI of the fetal eyes: morphologic and biometric assessment for abnormal development with ultrasonographic and clinicopathologic correlation

BACKGROUND: Currently ocular biometric measurements are defined by US and are measured from the orbital walls. These bony landmarks cannot be seen by MRI, and therefore these measurements cannot be directly applied. OBJECTIVE: To define measurements of normal growth of the fetal eyes using MRI. MATERIALS AND METHODS: Transorbital views were analyzed in 198 fetal MR examinations. The ocular diameter (OD) and interocular and binocular distances (IOD and BOD) were measured and were plotted against gestational age. Fetuses with abnormalities affecting the eyes were evaluated separately. RESULTS: Of 198 scans, 146 had suitable images, 35 of which were abnormal. Normal growth of BOD, IOD and OD were determined, and compared with the respective already established US data. CONCLUSION: Normal growth charts were derived from a cohort of 111 normal fetuses. Because the margins of the vitreous are inside the bony orbit, at the same gestational age measurements of the BOD and OD are always less than the corresponding measurements by US, and those of the IOD are always more. Normal growth charts for MRI can now be used to support suspected diagnoses of orbital and ocular pathologies and the syndromes that give rise to them, and many examples are demonstrated.     

Magnetic resonance techniques in the evaluation of the perinatal brain: recent advances and future directions

Magnetic resonance (MR) techniques are attractive for use in the developing brain because of their resolving power and their relative noninvasiveness. Their ability to provide detailed structural as well as metabolic and functional information without the use of ionizing radiation is unique. Conventional MR Imaging has widely proven its potential for identifying normal and pathologic brain morphology. Functional MR imaging such as diffusion-weighted imaging (DWI) and perfusion and blood-oxygenation-dependent BOLD imaging are newer imaging methods providing insights into brain physiology. This review will focus on the application of different MR techniques including the conventional structural MR imaging techniques and the more advanced MR techniques, such as the quantitative morphometric MR methods, the diffusion weighted MR techniques, the functional MR techniques and MR spectroscopy in the study of the fetal and newborn brain.     

3D perfusion mapping and virtual surgical planning in the treatment of pediatric embryonal abdominal tumors.

INTRODUCTION: 3D imaging and surgical planning for the treatment of embryonal tumors using different techniques (CT versus MRI) are presently under discussion. Up to now, the main focus has been on visualizing the anatomy. Contrast medium dynamics have not been taken into consideration. The aim of the present study was to establish the technical means of integrating the 3D images from functional MRI data into the anatomical images and to determine clinical applications for this approach. MATERIAL AND METHODS: In 11 patients (mean age: 2.4 years) with solid tumors, 26 diagnostic MRI examinations were performed for primary diagnosis, treatment monitoring, or as part of the surgical planning. Seven children presented with neuroblastomas, three with Wilms' tumor, and one with advanced bilateral nephroblastomatosis. The MRI data were acquired using a 1.5-T system. For post-processing, we used volume rendering software, including an evaluation of perfusion. By using color-coded parametric images and integrating functional information, perfusion could be visualized and used for interactive surgical planning. Macroscopic and microscopic sections served as the gold standard for assessing tissue viability. RESULTS: We were able to integrate the dynamic data into the anatomical images for all patients. A good agreement was found between the results of surgical planning, including perfusion mapping, with the surgical site, subsequently produced macroscopic sections and the results of random microscopic examinations. CONCLUSIONS: Perfusion mapping using color-coded parametric images of pediatric abdominal tumors extends the diagnostic techniques currently available. We provide first proof of the possibility of integrating functional information into 3D MR images in children. Monitoring the treatment of nephroblastoma and surgical planning for pediatric embryonal tumors represent potential applications of this technique.     

Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats

Intrauterine infection is a risk factor for developmental brain injuries in childhood. A variety of cytokines known to be toxic to developing brain cells have been isolated from mothers or children at risk for developmental disabilities, and these cytokines have been proposed as mediators of these injuries. We have developed a model of intrauterine inflammation that damages the developing white matter and we now hypothesize that selected cytokines are increased after our experimental inflammatory stimulus. Timed-pregnant Fischer 344 and Lewis rats were injected with 0.1 mg/kg of lipopolysaccharide (LPS) into the cervix at E15. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-10 were measured in homogenates of fetal brain and placenta at serial time periods within the first 24 h after the inflammatory stimulus. TNF-alpha was increased 20-fold in the placenta and more than 5-fold in the fetal brain after the stimulus. IFN-gamma was only increased within the fetal brain (20-fold) and IL-6 was only increased in the placenta (10-fold). IL-10 was mildly increased in the placenta and was decreased slightly in the fetal brain. Our observations show that an intrauterine inflammatory stimulus can cause large increases in Th1 cytokines within the fetal brain. The placenta can produce selected cytokines but fails to produce IFN-gamma, suggesting that the fetal immune system produces this cytokine in response to our stimulus. By studying placental and brain cytokine responses in models such as ours, the mechanisms responsible for the damage to developing white matter can be determined.     

Three-dimensional analysis of anorectal embryology

To clarify the embryological etiology of various malformations, we recently developed a computerized three-dimensional (3D) reconstruction system for analytical observation of real structures in a small fetus and applied this technique for the analysis of anorectal embryology. Fifty-one pig fetuses were obtained from two porcine families with anorectal malformations established in our facilities. They were sectioned sagitally and 3D structures of the anorectum were reconstructed from serial sections and analyzed. In the young pig embryo (24–30 days), the cloaca exists as a cloacal plate, a very thin, flat structure vertical to the body surface. It is filled with basophilic cells and contains no cavity. Therefore, the body surface covering the urogenital and rectal area may not be recognized as a single membranous structure. In the reconstructed image of the cloacal plate, the proximal part, which lies between the hindgut and tail groove, was defective in the specimens with anorectal anomalies whereas the cloacal plate existed from the entire anterior part to the posterior ene of the tail groove in the normal specimens. This result supports the theory of van der Putte that anorectal malformations are caused by a defect of the cloacal plate between the hindgut and tail groove. Correspondence to: H. Ohkawa     

Bifid choroid plexus: Always a normal fetal brain structure variant?

Choroid plexus, a fetal organ developing approximately from the sixth week of gestation, plays a fundamental role in developing fetal brain organization. As relatively little is known about the relationship between anomalies of choroid plexuses structure and their role in brain function, we examined cases of bifid choroid plexus (BCP) and discussed their potential association with lateral ventriculomegaly, other abnormal ultrasound findings, and their potential role as markers of fetal chromosomal abnormalities. In the present study, we described 23 cases of fetal BCP found in 2145 routine second trimester ultrasounds. For each patient 2D and 3D ultrasound volumes were acquired. BCP was defined as a choroid plexus whose body was divided into two portions (arms) differently located and oriented on the three spatial axes in correspondence to the lateral ventricle, in one or both sides. The entity of the separation and reciprocal orientation of the two arms was examined. The presence of BCP in a low‐risk population of pregnant women undergoing routine second trimester ultrasound was showed. Lateral ventricles significantly increased in the presence of BCP. Malformations were found in four of 23 fetuses with BCP. Pregnancy outcome was favorable only in one of these four cases. We suggest that in the presence of mono or bilateral BCP without associated abnormal ultrasound findings, a closer look at fetal brain or extra‐cranial structures is recommended. If no related abnormalities are found, serial prenatal and postnatal sonographic follow‐up should be considered. In the presence of concomitant abnormal findings, genetic counseling, fetal karyotyping and magnetic resonance imaging, if possible by gestational age, are strongly advised.     

Conventional magnetic resonance imaging in the differentiation between high and low-grade brain tumours in paediatric patients

ObjectiveIt has been described that hyperintensity in diffusion-weighted imaging (DWI) correlates with high-grade tumours, and high signal-intensity in T2-weighted (T2w) images identifies low-grade tumours. We aimed to investigate the potential of routine conventional MRI sequences, such as DWI and T2-w, to pre-operatively distinguish between low-grade and high-grade brain tumours in paediatric patients.Material and methodsTwo raters, blinded to the histological diagnosis, rated the aspect and signal intensity of MR images (T2w and DWI) from 37 children with newly diagnosed brain tumours. Histological diagnoses included 18 low-grade and 19 high-grade brain tumours.ResultsThe inter-rater agreement was 81–95%. High-grade tumours were never hypointense on DWI and low-grade tumours were usually hyperintense on T2w. Specificity was 100% for low-grade tumours and 90% for high-grade tumours. About 95% of the high-grade tumours and about 70% of the low-grade tumours were correctly diagnosed.ConclusionThe combination of general morphological aspect of the tumours and signals on T2-w and DWI yield a high accuracy of pre-operative differentiation between low-grade and high-grade paediatric tumours.     

Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome

For typically developing infants, the last trimester of fetal development extending into the first post-natal months is a period of rapid brain development. Infants who are born premature face significant risk of brain injury (e.g., intraventricular or germinal matrix hemorrhage and periventricular leukomalacia) from complications in the perinatal period and also potential long-term neurodevelopmental disabilities because these early injuries can interrupt normal brain maturation. Neuroimaging has played an important role in the diagnosis and management of the preterm infant. Both cranial US and conventional MRI techniques are useful in diagnostic and prognostic evaluation of preterm brain development and injury. Cranial US is highly sensitive for intraventricular hemorrhage (IVH) and provides prognostic information regarding cerebral palsy. Data are limited regarding the utility of MRI as a routine screening instrument for brain injury for all preterm infants. However, MRI might provide diagnostic or prognostic information regarding PVL and other types of preterm brain injury in the setting of specific clinical indications and risk factors. Further development of advanced MR techniques like volumetric MR imaging, diffusion tensor imaging, metabolic imaging (MR spectroscopy) and functional connectivity are necessary to provide additional insight into the molecular, cellular and systems processes that underlie brain development and outcome in the preterm infant. The adult concept of the "connectome" is also relevant in understanding brain networks that underlie the preterm brain. Knowledge of the preterm connectome will provide a framework for understanding preterm brain function and dysfunction, and potentially even a roadmap for brain plasticity. By combining conventional imaging techniques with more advanced techniques, neuroimaging findings will likely be used not only as diagnostic and prognostic tools, but also as biomarkers for long-term neurodevelopmental outcomes, instruments to assess the efficacy of neuroprotective agents and maneuvers in the NICU, and as screening instruments to appropriately select infants for longitudinal developmental interventions.     

Structural congenital brain disease in congenital heart disease: Results from a fetal MRI program

ObjectiveTo identify the type and incidence of fetal brain pathology in fetuses with a prenatal diagnosis of congenital heart disease (CHD).Patients and methods67 pregnant women underwent a fetal MR-examinations between 20 and 38 gestational weeks. MR was done on a 1.5 T superconducting system. The type of cardiac malformation was defined by fetal echocardiography. Fetuses with a chromosomal abnormality or an extracardiac anomaly were excluded.ResultsFetal MRI scans in the final study cohort (53 fetuses) yielded normal results in 32 fetuses and a brain abnormality in 21 fetuses. Congenital brain disease (CBD) was found in 39% of the final study cohort of fetuses with CHD. MRI findings were classified into malformations, acquired lesions and widening of the ventricles and/or outer CSF spaces (malformations: 7 fetuses, acquired lesions: 5 fetuses, changes in CSF spaces: 9 fetuses). Asymmetry of the ventricles was the most common finding in the CSF group.ConclusionsOur data suggest that fetal MRI can be used to characterize structural CBD in CHD. Advanced MRI techniques such as diffusion tensor imaging and proton spectroscopy are tools that, in the future, will certainly shed light on the spectrum of structural and functional CBDs that are associated with CHD.     

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目的应用MRI观察苯丙酮尿症(PKU)患儿脑髓鞘发育延迟与血苯丙氨酸(PHE)浓度的关系。方法对2002—2004年北京中日友好医院PKU门诊确诊的经典型PKU患儿29例,治疗前进行头颅MRI及血苯丙氨酸浓度检查,脑髓鞘发育按Staudt标准对不同年龄阶段患儿脑10个区域进行量化评估。HPLC法定量测定血PHE浓度。根据开始接受治疗年龄不同分为甲(28~48周,11例)、乙(49~390周,18例)两组,另随机选取其中19例治疗1年后复查MRI进行治疗前后对照,根据该19例治疗中血苯丙氨酸浓度控制情况分为A组(血PHE控制在0.12~0.48mmol/L)和B组(血PHE控制在0.12~0.48mmol/L以外)。结果29例患儿治疗前均存在髓鞘发育延迟,在10个脑区域髓鞘发育延迟平均发生率为45.6%,主要部位在脑叶和胼胝体,其中甲组髓鞘发育延迟平均发生率为40.8%,乙组发生率为51.2%,甲乙组间差异有显著性意义(P<0.05);经低苯丙氨酸饮食治疗1年后,19例10个脑区域髓鞘发育延迟平均发生率为32.2%;治疗前后髓鞘延迟有显著性改善(P<0.01),且治疗中血PHE浓度控制较好的A组髓鞘延迟改善率为1.75±0.66,B组病例为0.78±0.44,差异有显著性(P<0.01),髓鞘延迟改善与血PHE浓度间有密切相关性。结论治疗延迟的PKU患儿的脑髓鞘发育延迟的高发病率,与高血PHE浓度影响时间有关;经低苯丙氨酸饮食治疗延迟的改善率,与治疗中血PHE浓度控制情况直接影响延迟改善,因此提示PKU患儿血PHE浓度是影响脑髓鞘发育延迟发生及改善的重要原因。     

Brain morphology alterations in the basal ganglia and the hypothalamus following prenatal exposure to antiepileptic drugs.

If humans are exposed prenatally to antiepileptic drugs (AEDs), cognitive impairment may be the consequence. Driven by results of experimental work showing that AEDs may induce neuronal death in the developing rodent brain, we wanted to explore whether prenatal exposure to AEDs (PAE) may result in structural changes in the human brain. For this purpose we investigated a group of healthy young adults with PAE and a group of age-matched unexposed healthy controls by magnetic resonance imaging (MRI) of the brain. Local differences in cerebral morphology associated with PAE were analysed in volumetric MRI data by use of voxelwise comparisons of grey and white matter images. Significant regional decreases of grey matter volumes were found in PAE subjects in the area of the lentiform nucleus, including both pallidum and putamen bilaterally, and the hypothalamus. No significant regional differences in white matter volumes were found. We conclude that PAE causes subtle morphological changes in grey matter of the human brain which are conform with lower cell numbers in the basal ganglia and the hypothalamus.     

Magnetic resonance in pediatric research and clinical practice. II. Studies on the development and pathology of the brain in neonates, infants and young children

We are investigating metabolism and morphological differentiation of the developing brain in neonates and children under non-invasive conditions combining MR imaging (MRI) with spectroscopy (MRS) on a high-field/small-bore (2.35 Tesla/40 cm) system. By the end of 1987, 116 neonates, infants and young children with various perinatal problems, congenital abnormalities and different neurological diseases have been examined with MRI. In addition, MRS studies were subsequently performed on 46 of these children using the same instrument and within the same session. The small, sometimes very sick and instable patients require careful monitoring and elaborate technical devices in the high magnetic field. We are presenting solutions for methodological and technical developments and adaptations, concepts for sedation and measurement protocols in various age groups and first results of the combined use of MRI and MRS to investigate the brain in neonates and infants.