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Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases.

PURPOSE: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). The radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. RESULTS: The radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). CONCLUSIONS: The present study showed a potential value of prophylactic HBO for the radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit.

Adult↗

Traumatic brain injury.

Traumatic brain injury (TBI) is a serious health issue in the United States, killing 100,000 people a year and serving as a source of long-term disability for many more. It is the leading cause of death in patients under the age of 45 years. Successful management of TBI requires first an appreciation that a significant part of the neuronal injury incurred following trauma is secondary and is a result of disordered homeostatic mechanisms rather than the mechanical energy of the initial insult. Key skills in the care of brain-injured patients include adequately gauging the severity of injury, recognizing the primacy of sufficient blood flow and oxygen delivery to the injured brain, and being able to detect and correct when possible local and global physiological abnormalities that frequently put the injured brain at ongoing risk within the intensive care unit. This article discusses these issues, including invasive hemodynamic and intracranial monitoring, useful methods for reducing intracranial pressure, and management of complications arising from acute head injury.

Journal Article↗

Early predictors of mortality in penetrating compared with closed brain injury.

INTRODUCTION: Although brain injury incidence rates have been decreasing, the proportion of these injuries which are penetrating has been increasing. This study compares mortality amongst persons with penetrating and closed brain injuries and explores the relationship of early predictors of mortality. METHODS: The study included 795 moderately or severely brain injured individuals identified through the UCLA Brain Injury Research Centre. Logistic regression was used to predict mortality by GCS level and brain injury type, controlling for age, gender, and presence of multiple trauma. RESULTS: Of the 795 individuals, 110 had penetrating and 685 had closed brain injury. Case fatality rates were higher for penetrating than closed injuries for all GCS, gender, age, and cause of injury categories. When controlling for GCS level at admission, age, gender, and multiple trauma, those with penetrating injuries were 6.6 (95% CI = 3.9-11.1) times more likely to die. CONCLUSIONS: As the pool of information about survival and recovery from penetrating injuries grows, decisions regarding clinical care and prevention activities can be more appropriately focused.

Adolescent↗

Transcranial cytokine gradients in patients requiring intensive care after acute brain injury.

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

Acute Disease↗

Anti-epileptic drugs for preventing seizures following acute traumatic brain injury.

BACKGROUND: Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release. OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Medline and the databases of the Cochrane Stroke Group and Cochrane Epilepsy Group. We also contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the National Institute of Health, United States. SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the quality of the trials. Relative risks and 95% confidence intervals were calculated for each trial on an intention to treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension. MAIN RESULTS: We identified 10 eligible randomised controlled trials, including 2036 participants. Data are currently unavailable for four unpublished trials, representing 631 participants. For the remaining trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95% confidence interval 0.21 to 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR=1.15; 95% confidence interval 0.89 to 1. 51), a reduction in death and neurological disability (RR = 1.49; 95% confidence interval 1.06 to 2.08 for carbamazepine and RR= 0.96; 95% confidence interval 0.72 to 1.26 for phenytoin) or a reduction in late seizures (pooled RR =1.28; 95% confidence interval 0.90 to 1. 81). The pooled relative risk for skin rashes was 1.57 (95% confidence interval 0.57 to 39.88). REVIEWER'S CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.

Anticonvulsants↗

Neuronal injury and loss after traumatic brain injury: time course and regional variability.

We have examined regional neuronal injury after traumatic brain injury using Fluoro-Jade, an acidic dye that exhibits a marked affinity for both the degenerating neuronal cell body and its processes and have determined the extent to which early injury corresponds to regional patterns of neuronal loss. Rats (n=45) were subjected to lateral fluid percussion brain injury and euthanized at 3 h to 28 days post injury. Complementary Fluoro-Jade, silver impregnation methods and TUNEL were used to assess neuronal injury. Neuronal loss was evaluated in sections immunostained for NeuN, a neuronal specific nuclear protein. Overt neuronal cell loss was evident by 7 days post injury in the cortex, hippocampus and thalamus. Injured neurons were apparent in the ipsilateral cortex bordering the impact site, hippocampus (CA1 and dentate), thalamus, and vermis of the cerebellum as early as 3 h post injury. Degenerating neurons were maximal by 1 and 3 days in the cortex and hippocampus, by 3 and 7 days in the cerebellum, and by 7 days in the thalamus. The regional distribution of Fluoro-Jade-labeled neurons corresponded to a similar pattern of silver and TUNEL staining. Together, these findings demonstrate a regionally specific temporal pattern of neuronal injury that results in overt neuronal cell loss within both cortical and subcortical regions.

Animals↗

Corticosteroids for acute traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability. Corticosteroids have been widely used in treating people with traumatic brain injury. OBJECTIVES: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. SEARCH STRATEGY: Electronic sources: MEDLINE, EMBASE, Cochrane Library and specialised database searches. Additional hand searching and contact with trialists. Date of the most recent search October 2004. SELECTION CRITERIA: All randomised controlled trials of corticosteroid use in acute traumatic brain injury with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Quality of allocation concealment was scored. Data on numbers of participants randomised, numbers lost to follow up, length of follow up, case fatality rates, disablement, infections and gastrointestinal bleeds were extracted independently and checked. MAIN RESULTS: We identified 20 trials with 12303 randomised participants. The effect of corticosteroids on the risk of death was reported in 17 included trials. Due to significant heterogeneity we did not calculate a pooled estimate of the risk of death. The largest trial, with about 80% of all randomised participants, found a significant increase in the risk ratio of death with steroids 1.18 (1.09 to 1.27). For the nine trials that reported death or severe disability, the pooled relative risk was 1.01 (0.91 to 1.11), although this does not yet contain data from the largest trial. For infections the pooled risk ratio from five trials was 1.03 (0.99 to 1.07) and for the ten trials reporting gastrointestinal bleeding 1.23 (0.91 to 1.67). AUTHORS' CONCLUSIONS: In the absence of a meta-analysis, we feel most weight should be placed on the result of the largest trial. The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury.

Brain Injuries↗

Corticosteroids for acute traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability. Corticosteroids have been widely used in treating people with traumatic brain injury. OBJECTIVES: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. SEARCH STRATEGY: Electronic sources: MEDLINE, EMBASE, Cochrane Library and specialised database searches. Additional hand searching and contact with trialists. Date of the most recent search June 1999. SELECTION CRITERIA: All randomized controlled trials of corticosteroid use in acute traumatic brain injury with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Quality of allocation concealment was scored. Data on numbers of participants randomized, numbers lost to follow up, length of follow up, case fatality rates, disablement, infections and gastrointestinal bleeds were extracted independently and checked. MAIN RESULTS: We identified 19 trials with 2295 randomized participants. The effect of corticosteroids on the risk of death was reported in 16 included trials. The pooled relative risk for the 16 trials was 0.96 (95% confidence interval 0.85 to 1. 08). Pooled risk difference was 1.3% (5.2% to 2.5% more). For the nine trials that reported death or severe disability, the pooled relative risk was 1.01 (0.91 to 1.11). For infections the pooled relative risk was 0.94 (0.76 to 1.16) and for the nine trials reporting gastrointestinal bleeding 1.11 (0.54 to 2.26). Using only those trials with the best quality of allocation concealment, the pooled relative risk estimate for death became closer to unity. REVIEWER'S CONCLUSIONS: Neither moderate benefits nor moderate harmful effects of steroids can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible, and worthwhile, to establish whether there are any benefits from corticosteroids in this situation.

Brain Injuries↗

Cerebrospinal fluid enzymes in acute brain injury. 2. Relation of CSF enzyme activity to extent of brain injury.

The value of CSF enzyme estimations as indices of the extent of brain damage was studied in the experimental situation. Standard cold lesions of different severity were induced in cats. The activities of the enzymes CPK, HBDH, LDH, GOT, AND ChE were studied at half hour intervals in the cerebrospinal fluid (CSF). The ventricular and cisternal fluid pressure, and the arterial blood pressure were monitored continuously. Significantly higher enzyme levels were found in the animals with more severe injuries of the brain.

Alanine Transaminase↗

[Transcranial cytokine gradient and intestinal permeability in acute severe brain injury].

BACKGROUND: Acute brain injury is associated with a bimodal hypermetabolic state probably caused by cytokine secretion and high hormone and catecholamine concentrations. In a first stage, the brain would produce these substances and afterwards, another production source, most probably the splanchnic territory, would perpetuate the hypermetabolic state. AIM: To investigate the cytokine production source and to assess intestinal permeability in acute brain injury in the absence of cerebral ischemia and systemic oxygen deficit. PATIENTS AND METHODS: Arterial systemic and cerebral venous bulbar interleukin 1 beta and interleukin 6 levels were measured during the first seven days of evolution in 15 patients with acute brain injury. Serum lactate, the oxygen/lactate ratio, gastric intramucosal pH and intestinal permeability using the lactulose/mannitol test were also assessed in the same period. RESULTS: High arterial and venous interleukin 1 beta and interleukin 6 levels were detected. A positive gradient for interleukin 6 levels was detected throughout the study period with normal intramucosal pH, lactate and oxygen/lactate ratio. There was also an early impairment of intestinal permeability in these patients. CONCLUSIONS: High arterial and venous cytokine concentrations were detected in patients with acute brain injury. The positive gradient for interleukin 6 suggests a brain origin for this cytokine. Intestinal permeability is also altered in these patients.

Adult↗

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury.

OBJECTIVE: Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. PATIENTS AND METHODS: Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. RESULTS: Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. CONCLUSION: There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.

Adolescent↗

Phasic arousal in response to auditory warnings after traumatic brain injury.

Traumatic brain injury (TBI) is believed to have adverse effects on attention, but because of the multifaceted nature of the arousal and attentional network, the precise impact of TBI on various subcomponents of this network remains controversial. As part of a larger program of research on attention in TBI, we studied the effects of auditory warning signals on accuracy, reaction time, and response bias, as indices of phasic arousal in a visual go/no-go task. Warnings were presented randomly at various pre-stimulus intervals to a sample of recently injured patients and control subjects. For each subject and performance index, we examined the time interval required to reach maximal phasic arousal, the degree of performance change occurring at this maximal point, and the ability to maintain this state of increased arousal over longer warning intervals. After adjustment for baseline differences, there were no significant differences between patients and controls in any aspect of performance. Examination of effect sizes suggested that this was not due to limited statistical power, but that any differences between groups, if present, must have been small. In contrast, in our prior research on sustained attention and observable behaviors related to attention, large group differences have been found. These data suggest that mechanisms responsible for auditorily-induced phasic arousal responses are largely preserved in severe TBI.

Adult↗

Cell death in perinatal hypoxic-ischaemic brain injury.

Perinatal hypoxic brain injury is a major cause of death and morbidity, in which the onset of injury can be prenatal, and the effects may be delayed. Selective neuronal necrosis, with isolated karyorrhectic nuclei in the pons, is a common pattern of injury in mature perinatal deaths. Other evidence implicates apoptosis in hypoxic brain injury. In this study the mode of cell death in hypoxic injury was investigated in 11 fresh stillbirths and 10 neonatal deaths. Sections of pons were stained using several methods including terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) and immunocytochemistry. Karyorrhectic nuclei were counted on adjacent haemotoxylin and eosin sections. A high percentage of apoptotic cells was significantly associated with the presence of karyorrhexis in the pons, but there were five stillbirths in whom apoptosis in the pons was the sole evidence of hypoxic brain injury. PCNA positive neuronal nuclei were seen in 19 out of 21 cases. The results suggest that both apoptosis and necrosis are occurring following hypoxic injury, so that the pattern of injury in the pons may be better termed 'selective neuronal death'. Variations in severity and duration of the insult might explain the differences between cases. The presence of PCNA-positive neurons may suggest DNA repair in these nuclei, which might be activated at an early stage of apoptosis. However the precise mechanism by which apoptosis is induced in hypoxic brain injury remains to be elucidated.

Apoptosis↗

R3-survey of traumatic brain injury management in European Brain IT centres year 2001.

OBJECTIVE: To obtain knowledge about the conditions and management of traumatic brain injury (TBI) in a collaborative network of Brain Information Technology centres. DESIGN: The Brain IT (Brain monitoring with Information Technology) survey comprised two parts: local conditions and policies (part A), and a case study part (part B). The information was gathered by written questionnaires followed by telephone interviews. PARTICIPANTS: Twenty-four Brain IT centres participated (two respondents from 18 sites). RESULTS: The average proportion of agreement between duplicate respondents was 0.79 (range 0.44-1.00). All Brain IT centres monitored ICP. The reported order of treatment for intracranial hypertension was: evacuation of mass-lesions and head elevation (1), increase of sedation and Mannitol scheme (2), hyperventilation (3), ventricular drainage (4), craniectomy and pentothal coma (5), and decompressive lobectomy (6). The respondents were less prone to evacuate expansive contusions in relation to extra cerebral hematomas. The most common suggested interventions (alone or in combination) for treatment of intracranial hypertension without mass lesions was the Mannitol scheme (included in 71% of the suggestions), CSF drainage (included in 56%), hyperventilation (included in 32%), and pentothal coma (included in 22%). CONCLUSIONS: The suggested management of TBI was mainly in accordance with published guidelines, although a minor proportion of the answers deviated to some extent. The suggested order and combinations of different treatment interventions varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data as collected prospectively in a Brain IT database.

Adult↗

A pilot study on the effectiveness of tele-analogy-based problem-solving training for people with brain injuries.

People with brain injuries must often deal with cognitive problems, including social problem solving. The present study evaluated the effectiveness of a 20-session, online, interactive, skill-training programme on the solving of problems using analogies. It was hypothesized that the programme could help people with brain injuries learn better problem-solving skills through systematic, theoretically driven learning strategies. Fifteen Hong Kong-Chinese with brain injuries participated in this pilot study. They were randomly assigned to an online programme, a computer-assisted programme or a therapist-administered programme. The three programmes had a similar structure and contents, including basic components problem solving, reflective sessions and functional problem solving. Outcome measures included the Category Test of Halstead-Reitan Test Battery, and a daily problem-solving performance and self-efficacy checklist. The results showed that the subjects of the three programmes generally demonstrated higher post-training self-efficacy and basic problem-solving skills. The group using the online programme, however, showed better and quicker improvements in problem-solving performance, and demonstrated a general trend towards making fewer errors in complex problem-solving tasks. In conclusion, people with brain injuries can use the successful problem-solving experiences obtained in the training programmes with different delivery modes to solve daily living problems that are similar in nature. However, the generalizability of the effects of the programme is still to be determined.

Adolescent↗

Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury.

BACKGROUND: Traumatic brain injury is common and presents a health problem with significant effect on quality of life. Hyperbaric oxygen therapy (HBOT) has been suggested to improve oxygen supply to the injured brain and, therefore, to reduce the volume of brain that will ultimately perish. It is postulated that the addition of HBOT to the standard intensive care regimen may result in a reduction in patient death and disability as a result of these additional brain-preserving effects. OBJECTIVES: To assess the benefits and harms of adjunctive HBOT for treating traumatic brain injury. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library Issue 4, 2003), MEDLINE (1966 - 2003), EMBASE (1974 - 2003), CINAHL (1982 - 2003), DORCTHIM (1996 - 2003), and reference lists of articles. Relevant journals were handsearched and researchers in the field were contacted. SELECTION CRITERIA: Randomised studies comparing the effect on traumatic brain injury of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the validated Oxford-Scale (Jadad 1996) and extracted the data from the included trials. MAIN RESULTS: Four trials contributed to this review (382 patients, 199 receiving HBOT and 183 control). There was a trend towards, but no significant increase in, the chance of a favourable outcome when defined as full recovery, Glasgow outcome score 1 or 2, or return to normal activities of daily living (relative risk [RR] for good outcome with HBOT 1.94, 95% confidence interval [CI] 0.92 to 4.08, P=0.08). Pooled data from the three trials with 327 patients that reported mortality, showed a significant reduction in the risk of dying when HBOT was added to the treatment regimen (RR 0.69, 95% CI 0.54 to 0.88, P=0.003). Heterogeneity between studies was low (I(2) =0%), and sensitivity analysis for the allocation of dropouts did not affect that result. This analysis suggests we would have to treat seven patients to avoid one extra death (number needed to treat [NNT] 7, 95% CI 4 to 22). One trial suggested intracranial pressure was favourably lower in those patients receiving HBOT in whom myringotomies had been performed (WMD with myringotomy -8.2 mmHg, 95% CI -14.7 mmHg to -1.7 mmHg, P=0.01), while in two trials there was a reported incidence of 13% for significant pulmonary impairment in the group receiving HBOT versus 0% in the non-HBOT group (P=0.007). REVIEWERS' CONCLUSIONS: In people with traumatic brain injury, the addition of HBOT significantly reduced the risk of death but not of favourable clinical outcome. The routine application of HBOT to these patients cannot be justified from this review. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT.

Brain Injuries↗

Perception and memory of facial affect following brain injury.

Brain-lesioned patients and controls were shown a series of happy, sad, fearful, and angry faces and asked to identify verbally the facial emotion and later freely recall the affect when shown some of the faces having neutral expressions. Greater misperception of facial affect was associated with posterior lesions when bilateral lesions were removed from data analysis. Unilateral and bilateral frontal lesions, however, were associated with memory deficits for facial affect. As a group, right versus left hemisphere-lesioned patients were not different from each other in the perception or memory of facial affect. Right frontal lesions, however, seemed especially to disrupt recall of facial emotion.

Adult↗

Advances in postnatal neuroimaging: relevance to pathogenesis and treatment of brain injury.

The human brain is susceptible to a wide variety of insults. The permanent residua of these abnormalities are represented in dysfunction of one or more areas of neurodevelopment. A full understanding of normal brain development, mechanisms of brain injury, and consequences for subsequent brain development is required to determine which infants are at risk for neurodevelopmental handicap, and to monitor the effects of new treatments and management regimens designed to prevent these disabilities. Advanced magnetic resonance techniques, such as quantitative morphometric magnetic resonance techniques, diffusion-weighted magnetic resonance techniques, and magnetic resonance spectroscopy applied to the study of early human brain development have given us a better understanding of the pathophysiologic mechanisms of brain injury and its effects on subsequent brain development. Magnetic resonance imaging has provided an invaluable tool for the study of the fetal and newborn brain in vivo.

Asphyxia Neonatorum↗