Magnetic resonance in pediatric research and clinical practice. I. What can we expect from this new method?

Nuclear Magnetic Resonance (NMR) was first observed over 40 years ago and has recently also entered the field of human medicine. It currently attracts increasing attention from biologists and clinicians alike, and the scope of its different applications is in a phase of explosive development. Two principle developments of the MR method are taking place over the recent years and are of special interest for pediatricians and neonatologists. One involves the possibility of obtaining images from any part of the human body, somewhat similar to those obtained with computer tomography (CT), but without any radiation hazard. Today clinicians are most familiar with this mode of MR application. The other development tries to adapt the MR method of elucidating the structure of molecules used in physics, molecular biology and organic chemistry for applications in medicine, allowing to study metabolism in vivo under non-invasive conditions. Again, such studies pose no health hazards and are, therefore, applicable to neonates and small infants. They will enhance our understanding of metabolic processes during normal development and disease, especially in organs like the brain, where biopsies are virtually impossible. Recent developments combine the two methods mentioned above, in order to obtain morphological as well as metabolic information from the same organ at the same time, which may provide even better insight into pathophysiological mechanisms and their response to therapeutic measures. This article attempts to give an overview to the medical researcher, the clinician, and especially the pediatrician and neonatologist of what MR is and what we can expect from it.     

Magnetic resonance spectroscopy in pediatric neuroradiology: clinical and research applications

Magnetic resonance spectroscopy (MRS) offers a unique, noninvasive approach to assess pediatric neurological abnormalities at microscopic levels by quantifying cellular metabolites. The most widely available MRS method, proton (¹H; hydrogen) spectroscopy, is FDA approved for general use and can be ordered by clinicians for pediatric neuroimaging studies if indicated. There are a multitude of both acquisition and post-processing methods that can be used in the implementation of MR spectroscopy. MRS in pediatric neuroimaging is challenging to interpret because of dramatic normal developmental changes that occur in metabolites, particularly in the first year of life. Still, MRS has been proven to provide additional clinically relevant information for several pediatric neurological disease processes such as brain tumors, infectious processes, white matter disorders, and neonatal injury. MRS can also be used as a powerful quantitative research tool. In this article, specific research applications using MRS will be demonstrated in relation to neonatal brain injury and pediatric brain tumor imaging.     

Magnetic resonance and ultrasound brain imaging in preterm infants

Cranial ultrasonography has been used to identify brain injury in preterm neonates for more than two decades. More recently, magnetic resonance imaging has been used to evaluate brain development and pathology in these infants. In this review we describe how well findings from these two imaging modalities agree with histology findings and neuro-developmental outcome. In addition, we discuss studies comparing ultrasound and magnetic resonance imaging findings.     

Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. A prospective study

We assessed the morphologic findings of the brain prospectively before and after cardiac surgery using magnetic resonance imaging. There were 12 patients with acyanotic and 6 with cyanotic heart disease. There were 2 deaths, and 1 patient did not have to undergo postoperative magnetic resonance imaging. The study group consisted of 15 patients completing both the preoperative and postoperative magnetic resonance imagings. All patients in the study group underwent moderate hypothermic cardiopulmonary bypass using a nonpulsatile membrane oxygenator. The mean (+/- SD) cardiopulmonary bypass time was 100 +/- 55 minutes. Ten of the preoperative studies were interpreted as normal. One third (5 of 15) of the patients showed ventriculomegaly and dilatation of the subarachnoid spaces on preoperative magnetic resonance images. Measurements of the preoperative and postoperative magnetic resonance images showed a postoperative increase in the bicaudate and third ventricular diameters. Four patients in the study group developed postoperative subdural hematomas. The subdural hematomas were small and caused no demonstrable mass effect on magnetic resonance imaging. One patient had a preoperative white matter infarction. There was 1 patient with a postoperative infarction.     

Magnetic resonance imaging of the brain of newborn infants

The authors report their experience of cerebral magnetic résonance imaging (MRI) in the neonatal period. MRI offers many advantages compared to CT scan or ultrasonography in the study of malformations, tumors, infections and anoxic-ischemic brain injury. However, MRI is limited by the duration of the examination the need for total immobility which is achieved in the neonate via administration of chloral hydrate, and lack of accessibility. MRI is a non invasive method for following in vivo brain development during infancy.     

Sonography of brain tumors in infants and young children

The sonographic features of five brain tumors are presented to emphasize the variability of imaging findings and the role that sonography may play in the initial diagnosis, determination of tumor vascularity, and biopsy guidance. Received: 14 August 2000 Accepted: 23 January 2001     

Magnetic resonance imaging of the brain in a cohort of extremely preterm infants.

To define magnetic resonance imaging (MRI) appearances of the brain in extremely preterm infants between birth and term, a sequential cohort of infants born at a gestational age <30 weeks was studied with a dedicated neonatal magnetic resonance scanner. Images of infants (n = 41) with a median gestational age of 27 weeks (range 23 to 29 weeks) were initially obtained at a median age of 2 days (range 1 to 20 days) and then repeatedly studied; 29 (71%) infants had MRI at a median gestational age of 43 weeks (range 38 to 52 weeks) (term MRI). On the initial MRI scan 28 of 41 infants had abnormalities: either intraventricular hemorrhage, germinal layer hemorrhage, ventricular dilatation, or diffuse and excessive high signal intensity in the white matter on T(2)-weighted images. When magnetic resonance images for preterm infants at term gestation were compared with those of infants in the control group born at term, 22 of 29 infants had dilatation of the lateral ventricles, 24 of 29 had squaring of the anterior or posterior horns of the lateral ventricles, 11 of 29 had a widened interhemispheric fissure or extracerebral space, and 22 of 29 had diffuse and excessive high signal intensity in the white matter. There were no cases of cystic periventricular leukomalacia. We conclude that MRI abnormalities are commonly seen in the brain of preterm infants on whom images are obtained within 48 hours of birth and that further abnormalities develop between birth and term. A characteristic appearance of diffuse and excessive high signal intensity in the white matter on T(2)-weighted images is associated with the development of cerebral atrophy and may be a sign of white matter disease. These MRI appearances may help account for the high incidence of neurodevelopmental impairment in extremely preterm infants.     

Magnetic resonance imaging in the pediatric patient.

Magnetic resonance imaging is an excellent technique for evaluation of pediatric pathology. When combined with other imaging modalities, MRI represents a powerful addition to the radiologist's diagnostic armamentarium. Magnetic resonance imaging has demonstrated great potential for noninvasively characterizing physical and chemical properties of various tissues and in some cases has provided information not available by any other technique. Future developments may result in much faster scan times, better biochemical characterization (magnetic resonance spectroscopy), and improved images. Certainly, the full potential of this extraordinary imaging technique has not been reached. As prospective studies of MRI evolve, this technique will play an increasing role in assessing pediatric disease.     

Developmental surveillance of infants and young children in pediatric primary care

PURPOSE OF REVIEW: This article reviews the importance of appropriate developmental surveillance in early childhood, what is known about its effectiveness in current pediatric practice, and ways in which its delivery can be improved to optimize child outcomes. RECENT FINDINGS: Many infants and young children with developmental delays or risk factors for poor developmental outcomes are not identified by pediatric practitioners in a timely manner. When they are identified, they are often not referred to appropriate early intervention services or early childhood development programs. They are therefore denied the opportunity to benefit from programs documented to have long-lasting benefits for children. Structuring developmental screening around the use of validated parent questionnaires improves the rates at which children with developmental needs are appropriately identified. At the same time, lowering thresholds for referral improves the rates at which children with identified needs receive appropriate services. SUMMARY: Pediatric practitioners are uniquely positioned to improve children's developmental outcomes through early identification and referral of children with developmental delays or risk factors for poor developmental outcomes. Unfortunately, inappropriate screening practices, high thresholds for referral, misplaced concerns about causing parental anxiety, and unfamiliarity with local resources all diminish the effectiveness with which many practitioners conduct developmental surveillance. Recent studies show that small changes in screening and referral practices have the potential to greatly improve the effectiveness of developmental surveillance. This, in turn, has the potential to improve lifelong outcomes for children.     

Ventricular dysfunction clinical research in infants, children and adolescents

These two issues of Progress in Pediatric Cardiology comprehensively illustrate the wealth of currently available information on the pathophysiology of heart failure, age-related myocardial responsiveness, energy metabolism, cardiopulmonary interactions, the pressure-volume relationship, the systemic inflammatory response, the management of heart failure, pediatric pharmacology, the use of heart failure therapies including digoxin, ACE inhibitors, beta-adrenergic blockers, inotropic agents, diuretics, vasodilators, calcium sensitizers, angiotensin and aldosterone receptor blockers, growth hormone, and future gene therapy. The etiology and course of ventricular dysfunction in children is poorly characterized. Furthermore, many changing developmental properties of the pediatric myocardium and differences in the etiologies of ventricular dysfunction in children compared with adults are illustrated in these articles, invalidating the concept that children can safely be considered small adults for the purpose of understanding heart failure pathophysiology and treatment. However, these articles reveal that strikingly little research in children with ventricular dysfunction exists in terms of well-designed large-scale studies of the epidemiology or multicenter controlled clinical therapeutic trials. A future research agenda is proposed to improve understanding etiologies, course and treatment of ventricular dysfunction in children that is based on organized and funded cooperative groups since no one pediatric cardiac center treats enough children with a particular etiology of ventricular dysfunction. In conclusion, significant understanding of basic mechanisms of pediatric ventricular dysfunction and effective therapies for adults with ventricular dysfunction exist. A multicenter pediatric cardiac ventricular dysfunction network would allow improved understanding of diseases and treatments, and result in evidence-based medicine for pediatric patients with ventricular dysfunction.     

Studies on the concentrations of chloramphenicol in the serum and cerebrospinal fluid of neonates,infants, and small children

The interactions between chloramphenicol, penicillin and phenobarbitone were investigated in 383 children (premature and neonate children, infants and small children). As expected, the chloramphenicol concentrations in the serum of the newborns was considerably higher than that of infants and small children with the same dosage of chloramphenicol. In the age group of the premature and newborn children and infants there were significantly higher total chloramphenicol concentrations with the chloramphenicol-penicillin combination than with chloramphenicol monotherapy. Addition of phenobarbitone to the combination significantly reduced the chloramphenicol concentrations in the neonates. Lowering of the serum chloramphenicol concentrations by phenobarbitone could not be statistically confirmed in the infant age group.Combinations of chloramphenicol with ampicillin, gentamycin or cephalosporin derivatives showed no influence on serum chloramphenicol concentrations.Transference of chloramphenicol from the serum to the cerebrospinal fluid was about twice as high in the acute inflammatory stage as when the meninges were no longer acutely diseased (60 and 30% respectively of the serum concentrations). The passage of chloramphenicol to the cerebrospinal fluid showed no dependence on age.

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Zusammenfassung In Untersuchungen an 383 Kindern (Früh- und Neugeborenen, Säuglingen und Kleinkindern) wurde die Wechselwirkung zwischen Chloramphenicol und Penicillin sowie Phenobarbital geprüft. Erwartungsgemäß lagen bei gleicher Chloramphenicoldosierung die Chloramphenicolkonzentrationen im Serum neugeborener Kinder erheblich über denen der Säuglinge und Kleinkinder. In der Altersklasse der Früh- und Neugeborenen sowie der Säuglinge traten unter Chloramphenicol-Penicillin-Kombination signifikant höhere Gesamtchloramphenicolkonzentrationen auf als bei Chloramphenicol-Monotherapie. Zugabe von Phenobarbital zu der Kombination verringerte bei Neugeborenen signifikant die Chloramphenicolkonzentrationen. Die Erniedrigung der Chloramphenicolserumkonzentrationen unter Phenobarbital konnte bei der Altersgruppe der Säuglinge nicht statistisch gesichert werden.Keinen Einfluß auf die Chloramphenicolserumkonzentrationen zeigten Kombinationen von Chloramphenicol mit Ampicillin, Gentamycin oder Cephalosporinderivaten.Der Übertritt von Chloramphenicol aus dem Serum in den Liquor war in der akuten Entzündungsphase etwa doppelt so hoch wie bei nicht mehr akut erkrankten Meningen (60 bzw. 30% der Serumkonzentrationen). Eine Altersabhängigkeit der Liquorpassage von Chloramphenicol konnte nicht gesehen werden.

     

Coronary artery fistulas in neonates,infants, and children: clinical findings and outcome

Ten patients were diagnosed with coronary artery fistula (CAF) between 1991 and 1998 in our department. The ages of patients ranged from 3 days to 12 years. Five patients were male and five patients were female. Nine patients had single CAF and 1 patient had dual CAFs. CAFs of 7 patients originated from the left coronary artery, and CAFs of 3 patients originated from the right coronary artery. CAFs of 7 patients terminated at the right ventricle, CAFs of 2 patients terminated at the right atrium, and the CAF of 1 patient terminated at the pulmonary artery. Four patients were diagnosed with CAF in the neonate period. All presented with congestive heart failure. Medical therapy was successful in treating congestive heart failure in 2 of these patients, but the other 2 needed operations. One patient presented with subacute bacterial endocarditis at 12 years of age requiring surgical intervention. One patient had a large left-to-right shunt that was surgically repaired. One patient with dual CAFs underwent coil embolization and the larger CAF achieved complete embolization, but the smaller CAF failed. Follow-up data revealed that 1 patient who received an operation died of sepsis due to recurrent bronchiolitis 6 months later. Nine patients were asymptomatic. Because complications including endocarditis may be encountered in later life, we suggest early closure with coil embolization.     

Magnetic resonance imaging of the brain in newborn infants: Practical aspects

Magnetic Resonance Imaging is becoming more widely available and increasingly important for imaging the neonatal brain. In newborn infants it poses challenges regarding patient preparation, safety, optimal timing, and sequence optimization. These issues are addressed in this paper and indications for performing neonatal Magnetic Resonance Imaging are presented.     

Brain mapping in sedated infants and young children with passive-functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) in pediatric patients presents a unique set of problems due to the need for patient compliance, the frequent need for sedation and an early developmental status. A new method for using fMRI in sedated infants and young children is presented using passive stimuli focused on visual, sensorimotor and language functions. All of these stimuli are presented such that no patient interaction is required. Eight sedated children undergoing diagnostic MRI scans of the brain participated in these passive fMRI procedures. Cortical regions were identified using standard techniques applied to the blood-oxygen-level-dependent signal which is the basis for fMRI. The results support the feasibility of brain mapping in sedated children with passive fMRI techniques.