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Biomedical subjects

M A Rutherford

Publications and source records attributed to M A Rutherford.

At least 19 recordsLinked to original sources

Intrauterine T-cell activation and increased proinflammatory cytokine concentrations in preterm infants with cerebral lesions.

Brain injury is common in very preterm infants, and intrauterine infection is a frequent antecedent of preterm birth. We examined the relation of cerebral damage to intrauterine antigen exposure and inflammation in 50 infants who were born at 23-29 weeks' gestation. Higher concentrations of cytokines (tumour necrosis factor alpha [TNF-alpha], and interleukins [IL], 1beta, 6, and 10) and CD45RO(+) T lymphocytes in umbilical blood predicted cerebral lesions detected by magnetic resonance imaging very soon after delivery. Our results suggest that infants who mount an immune response in utero are at higher risk of cerebral lesions.

Brain Injuries↗

Diffusion-weighted imaging in neonates.

Diffusion-weighted imaging (DWI) can readily be performed in the neonate, although currently studies remain a few years behind-those carried out on adults. DWI relies on the random diffusion of water molecules. As for the adult population, a pulsed gradient spin echo sequence (PGSE) with cardiac gating can be used to exploit the effect of diffusion on image contrast and to determine the apparent diffusion coefficient (D*) for tissues or fluids. Anisotropic properties caused by the restriction of the movement of water molecules may be demonstrated. In the neonatal brain restricted motion can be detected in both myelinated and unmyelinated white matter tracts. DWI has been used to study changes in global and focal ischaemic injury to the neonatal brain. A decreased D* may be documented after an ischaemic insult followed by a gradual increase. These changes are consistent with animal data but show a slower time course. Intervention following perinatal ischaemic injury must be started within hours. DWI detects early ischaemic injury and may therefore be a useful tool for identifying those infants who could benefit from intervention.

Brain↗

How to perform diffusion-weighted imaging.

Diffusion-weighted imaging (DWI) has become an invaluable tool in the management of patients with stroke. DWI relies on detecting the random diffusion of water molecules. In normal tissues this movement may be restricted by the presence of cellular structures, which provide a barrier to free movement. This occurs in myelinated white matter, where movement is restricted more across than along fibres. This directional dependence is termed anisotropic restricted diffusion. The diffusion of water molecules can be made the dominant contrast mechanism within an image by applying large magnetic field gradients. The pulsed gradient spin echo (PGSE) sequence provides sensitivity to diffusion with gradient pulses either side of the 180 degrees refocusing pulse. This sequence is generally heavily T2 weighted. In order to detect normal anisotropic properties within the different components of the medullary core, association, commissural and projection fibres, DWI must be performed with sensitisation in at least three directions. PGSE sequences have been used to obtain the diffusion coefficient (D*), a measure of mobility at the molecular level within tissue. In acute infarction D* is increased; in brain death it is decreased. Diffusion contrast needs to be optimised in relation to the highly T2-dependent nature of PGSE sequences. This also requires a more detailed knowledge of how D* changes in disease, but information on nonischaemic neurological conditions is still very limited.

Adult↗

Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants.

OBJECTIVE: To compare findings on hard copies of cranial ultrasound (US) and magnetic resonance imaging (MRI) obtained between birth and term in a group of preterm infants. PARTICIPANTS AND METHODS: Infants born at or below a gestational age of 30 weeks who underwent cranial US scan and MRI on the same day were eligible for this study. Infants underwent, whenever possible, 3 scans between birth and term. We calculated the predictive probability (PP) of US findings as a predictor of findings on MRI. RESULTS: Sixty-two paired MRI and US studies were performed between birth and term in 32 infants born at a median gestational age of 27 (range: 23-30) weeks and a median birth weight of 918 (530-1710) grams. US predicted some MRI findings accurately: germinal layer hemorrhage (GLH) on US had a PP of 0.8 with a 95% confidence interval of (0.70-0.90) for the presence of GLH on MRI, intraventricular hemorrhage (IVH) on US had a PP of 0.85 (0.76-0.94) for the presence of IVH on MRI, and severe white matter (WM) echogenicity on US had a PP of 0.96 (0.92-1.0) for the presence of WM hemorrhagic parenchymal infarction on MRI. Other MRI changes were less well-predicted: mild or no WM echogenicity on US had a PP of 0.54 (0.41-0.66) for the presence of normal WM signal intensity on MRI, and moderate or severe WM echogenicity on US had a PP of 0.54 (0.42-0.66) for the presence of small petechial WM hemorrhage and/or diffuse excessive high-signal intensity (DEHSI) in the WM on T2-weighted images on MRI. However, mild/moderate or severe WM echogenicity on US scans performed at >/=7 days after birth had a PP of 0.72 (0.58-0.87) for the presence of WM hemorrhage and/or DEHSI on MRI. There were no cases of cystic periventricular leukomalacia. CONCLUSION: US accurately predicted the presence of GLH, IVH, and hemorrhagic parenchymal infarction on MRI. However, its ability to predict the presence of DEHSI and small petechial hemorrhages in the WM on T2 weighted images is not as good, but improves on scans performed at >/=7 days after birth. In addition, normal WM echogenicity on US is not a good predictor of normal WM signal intensity on MRI.

Brain↗

Diffusion-weighted imaging of the brain in neonates and infants.

Diffusion-weighted imaging provides novel and interesting insights into normal development and pathologic processes occurring in neonates and infants. Both myelinated and unmyelinated white matter show restricted diffusion. Focal infarction in perinatal stroke and more global injury associated with hypoxic ischemia encephalopathy produce high-signal lesions in the brain, in the acute phase. Diffusion-weighted imaging also demonstrates abnormalities of a variety of other diseases, when conventional imaging is relatively uninformative.

Brain↗

Reduced development of cerebral cortex in extremely preterm infants.

Most growth in cortical connections and complexity occurs after 25 weeks. The cerebral cortex of extremely preterm infants when imaged at gestational age 38-42 weeks had less cortical surface area and was less complex than in normal infants born around term (p<0.0148 and p<0.0002, respectively), despite similar term-corrected cerebral tissue volumes. Since deficits acquired during critical periods of brain development may be permanent, these results suggest a neural substrate for the neurocognitive impairment that is frequent among such preterm infants.

Cerebral Cortex↗

Head growth in infants with hypoxic-ischemic encephalopathy: correlation with neonatal magnetic resonance imaging.

OBJECTIVES: The aims of the study were to establish the relationship between head growth in the first year of life with the pattern on injury on neonatal magnetic resonance imaging (MRI) in infants with hypoxic-ischemic encephalopathy (HIE) and to relate these to the neurodevelopmental outcome. METHODS: Fifty-two term infants who presented at birth with a neonatal encephalopathy consistent with HIE and who had neonatal brain MRI were entered into the study. Head circumference charts were evaluated retrospectively and the head growth over the first year of life compared with the pattern of brain lesions on MRI and with the neurodevelopmental outcome at 1 year of age. Suboptimal head growth was classified as a drop of >2 standard deviations across the percentiles with or without the development of microcephaly, which was classified as a head circumference below the third percentile. RESULTS: There was no statistical difference between the neonatal head circumferences of the infants presenting with HIE and control infants. At 12 months, microcephaly was present in 48% of the infants with HIE, compared with 3% of the controls. Suboptimal head growth was documented in 53% of the infants with HIE, compared with 3% of the controls. Suboptimal head growth was significantly associated with the pattern of brain lesions, in particular to involvement of severe white matter and to severe basal ganglia and thalamic lesions. Suboptimal head growth predicted abnormal neurodevelopmental outcome with a sensitivity of 79% and a specificity of 78%, compared with the presence of microcephaly at 1 year of age, which had a sensitivity of only 65% and a specificity of 73%. The exceptions were explained by infants with only moderate white matter abnormalities who had suboptimal head growth but normal outcome at 1 year of age and by infants with moderate basal ganglia and thalamic lesions only who had normal head growth but significant motor abnormality.

Apgar Score↗

Pilot study of treatment with whole body hypothermia for neonatal encephalopathy.

BACKGROUND: There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia. However, clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia. OBJECTIVES: The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth, and to observe the effect of this therapy on relevant physiologic variables. METHODS: Sixteen newborn infants with clinical features of birth asphyxia (median cord blood pH: 6.74; range: 6.58-7.08) were assessed by amplitude integrated electroencephalography (aEEG), and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome. Rectal temperature was maintained at 33.2 +/- (standard deviation).6 degrees C for 48 hours. Rectal and tympanic membrane temperature, blood pressure, heart rate, blood gases, blood lactate, full blood count, blood electrolytes, high and low shear rate viscosity, and coagulation studies were monitored during and after cooling. A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging (MRI) and neurological examination. RESULTS: All infants selected to receive hypothermia developed convulsions and a severe encephalopathy. During 48 hours of hypothermia infants had prolonged metabolic acidosis (median pH: 7.30; base excess: -6.3 mmol x L(-1), a high blood lactate (median lactate: 5.3 mmol x L(-1)) and low blood potassium levels (median value: 3.9 mmol x L(-1)) x Hypothermia was associated with lower heart rate and higher mean blood pressure. However, these changes did not seem to be clinically relevant and no significant complication of hypothermia was encountered. Blood viscosity and coagulation studies were similar during and after cooling. Unusual MRI findings were noted in 3 infants: transverse sinus thrombosis with subsequent small cerebellar infarct; probable thrombosis in the straight sinus; and hemorrhagic cerebral infarction. Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination; 3 infants died and 1 had major abnormalities. None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel. CONCLUSIONS: After birth asphyxia infants can be objectively selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy. Prolonged mild hypothermia to 33 degrees C to 34 degrees C is associated with minor physiologic abnormalities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted.

Asphyxia Neonatorum↗

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.

Age Factors↗

Periventricular haemorrhagic infarct in a preterm neonate.

Magnetic resonance imaging (MRI) was performed on an infant born, at 28 weeks gestational age who suffered a sudden episode of bradycardia and desaturation on the 3rd day of life. Imaging demonstrated bilateral germinal layer haemorrhage and intraventricular haemorrhage, with parenchymal involvement in a fan-shaped pattern in the periventricular white matter on the left. These appearances are consistent with a combination of intravascular thrombi and perivascular haemorrhage along the course of the medullary veins. We believe that this is the first report of the MRI appearance of an acute periventricular haemorrhagic infarct associated with a germinal layer haemorrhage/intraventricular haemorrhage in a preterm neonate.

Cerebral Hemorrhage↗

Reproducibility and accuracy of MR imaging of the brain after severe birth asphyxia.

BACKGROUND AND PURPOSE: MR imaging of the brain can be used to detect cerebral damage after suspected hypoxic-ischemic injury. This study examines the reproducibility and accuracy of MR imaging soon after severe birth asphyxia. METHODS: During a 48-month period, full-term newborn neonates, who died within the first week as a result of severe hypoxic ischemic encephalopathy, were included in the study if they had undergone early (<5 days old) MR imaging and postmortem neuropathologic studies. Two trained observers assessed reproducibility by examining multiple brain regions independently with current criteria and then defining and applying improved criteria. Accuracy of MR findings was tested by comparing the brain regions about which the two imaging raters agreed to those regions about which the two pathologists agreed. RESULTS: Eight neonates, with a median gestational age of 40 weeks (range, 38-40 weeks) and who suffered severe birth asphyxia, were included in the study. In the reproducibility study, MR imaging agreement was moderate when current criteria were used (k = .44). Using the improved criteria, agreement increased considerably (k = .62). Much of this improvement was due to limiting the analyses to the posterior limb of the internal capsule, thalamus, parietal cortex, hippocampus, and medulla. The posterior limb of the internal capsule was the most reliable region analyzed. MR imaging agreement was similar to that achieved by two experienced pathologists reviewing the histologic sections (k = .66). In the accuracy study, MR imaging abnormality was predictive of pathologic abnormality with a sensitivity of .79 and a positive predictive value of 1.0. The predictive value of a single MR imaging abnormality was .79 (95% confidence interval, .61-.96). CONCLUSION: Criteria that provide substantial reproducibility and accuracy for the interpretation of MR imaging findings very early after birth asphyxia can be derived.

Asphyxia Neonatorum↗

Relationship between MR imaging and histopathologic findings of the brain in extremely sick preterm infants.

BACKGROUND AND PURPOSE: MR imaging can now be used safely in extremely preterm infants. The aim of this study was to compare the MR imaging appearance of the immature brain with neuropathologic findings at postmortem examination. METHODS: Seven extremely sick preterm infants, born at a median of 24 weeks' gestation, were studied using T1- and T2-weighted MR sequences. Infants died at a median of 3 days after initial MR imaging, and postmortem examinations were carried out. RESULTS: The cortex and germinal matrix were seen as areas of low signal intensity on T2-weighted images, which corresponded to their highly cellular histologic appearance. The periventricular and subcortical layers of white matter had a high signal intensity, corresponding to high fiber and relatively low cellular density; the intermediate layer of low signal intensity corresponded to a dense band of migrating cells. Regions of acute hemorrhage were seen as low signal intensity and regions of infarction as high signal intensity on T2-weighted images. One infant with mild periventricular leukomalacia had some low signal intensity on T1-weighted images, but no focal changes on T2-weighted images. Regions of neuronal mineralization, seen in association with infarction and capillary proliferation, within the basal ganglia and thalami were characterized by very low signal intensity on T2-weighted images and by very high signal intensity on T1-weighted images. There were no imaging abnormalities detected in regions with more subtle histologic abnormalities, such as increased glial or apoptotic cells. CONCLUSION: MR imaging can be used to observe normal developing brain anatomy in extremely premature infants; it can detect areas of hemorrhage and infarction within the developing brain, but conventional MR imaging may not detect more subtle histologic abnormalities.

Brain↗

Persistent increases in cerebral lactate concentration after birth asphyxia.

In this prospective study proton magnetic resonance spectroscopy (1H MRS) was used to test the hypothesis that lactate can be detected later than 1 mo after birth in the brains of infants who display severe neurodevelopmental impairment 1 y after transient perinatal hypoxia-ischemia. Data were obtained from three groups of infants: 1) eight infants suffering birth asphyxia followed by perinatal encephalopathy and abnormal neurodevelopmental outcome at 1 y of age (defined as major neurologic impairment, Griffiths quotient <85%, and low optimality score); 2) 10 infants with signs of perinatal hypoxia-ischemia but normal neurodevelopmental outcome at 1 y; and 3) six control infants with uneventful perinatal courses and normal neurodevelopment at 1 y. Between one and four examinations (median 1) were performed at median (range) 11 (4-68) wk after birth, and the cerebral concentration ratio of lactate to creatine plus phosphocreatine (Cr) calculated from each spectrum. Lactate was detected later than the 1st mo after birth in seven of eight infants with abnormal neurodevelopmental outcome [maximum detected lactate/Cr was median (range) 0.44 (0.24-0.67)]. No lactate was detected later than the 1st mo after birth in infants with normal neurodevelopmental outcome, nor in five of six control subjects, although a small amount of lactate was detected in one control infant (lactate/Cr=0.04). These results suggest that the pathologic postasphyxial process, indicated by persistent cerebral lactate, may not be confined to the period immediately after injury.

Asphyxia Neonatorum↗

Magnetic resonance imaging of the brain in very preterm infants: visualization of the germinal matrix, early myelination, and cortical folding.

OBJECTIVE: To investigate preterm infants, we have installed in our neonatal intensive care unit a dedicated magnetic resonance (MR) imaging system which was specifically designed for neonatal use. The aim of this study was to describe the MR appearances of the brain in preterm infants who were first scanned between 25 and 32 weeks gestational age (GA) and to outline changes to the brains of these infants between their first scan and term. METHODS: Preterm infants of 25 to 32 weeks GA were imaged using the 1T neonatal MR system (Oxford Magnet Technology, Eyensham, Oxfordshire, England/Picker International, Cleveland, OH). The scanning protocol included T1-weighted conventional spin echo (repetition time [TR], 600; echo time, 20 ms), inversion recovery fast spin echo (TR, 3530; effective echo time, 30; inversion time, 950 ms), and T2-weighted fast spin echo (TR, 3500; effective echo time, 208 ms) sequences. RESULTS: Seventeen infants of median 28 weeks GA (range, 24 to 31 weeks) at birth were imaged a total of 53 times between birth and term. The median number of images per infant was two (range, 1 to 9). In infants of < 30 weeks GA, the germinal matrix was visualized at the margins of the lateral ventricles. It had a short T1 and short T2 and the bulk of it involuted at between 30 and 32 weeks GA. The white matter had a relatively homogeneous low signal except for bands of altered signal (probably originating from regions containing radial glia and migrating cells) which were most apparent anterolateral and posterolateral to the lateral ventricles. Myelination was seen in the posterior brainstem, cerebellum, and region of the ventrolateral nuclei of the thalamus. Infants had very little cortical folding at 25 weeks GA but this developed later in an orderly fashion. CONCLUSION: The neonatal MR system allowed extremely preterm infants to be studied safely with MR imaging. The images acquired demonstrated the germinal matrix, early myelination, and early cortical folding. Evolution of these features was demonstrated with serial studies.

Brain↗

Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: The aim of this study was to establish whether abnormal signal intensity in the posterior limb of the internal capsule (PLIC) on magnetic resonance imaging is an accurate predictor of neurodevelopmental outcome at 1 year of age in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: We have examined 73 term neonates with HIE between 1 and 17 days after birth with cranial magnetic resonance imaging and related the magnetic resonance imaging findings to neurodevelopmental outcome at 1 year of age. RESULTS: All infants with an abnormal signal intensity in the PLIC developed neurodevelopmental impairment although in 4 infants with very early scans the abnormal signal was not apparent until up to 4 days after birth. A normal signal intensity was associated with a normal outcome in all but 4 cases; 3 of these infants had minor impairments and all had persistent imaging changes within the white matter. The 4th infant with a normal signal intensity on day 2 died before a further image could be obtained. The absence of normal signal predicted abnormal outcome in term infants with HIE with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87. The test correctly predicted outcome in 93% of infants with grade II HIE, according to the Sarnat system. Applying a Bayesian approach, the predictive probability of the test (the probability that the test would predict an outcome correctly) was distributed with a mean of 0.94 and 95% confidence limits of 0.89 to 1.0. CONCLUSION: Abnormal signal intensity in the PLIC is an accurate predictor of neurodevelopmental outcome in term infants suffering HIE.

Basal Ganglia↗

Does the brain regenerate after perinatal infarction?

We have used registered serial magnetic resonance scans to assess the growth of the brain after perinatal infarction in six infants. The initial scans were performed at ages of 4 days to 8 weeks and follow-up studies were performed from 4 days to 21 weeks later. A three-dimensional volume acquisition was performed on each occasion. Rigid body translations and rotations were used to match the images obtained on each occasion. Subtraction of the first image from the second then provided an assessment of the growth of the brain that had occurred between the two examinations. In the early phase of infarction (up to 2 months) low signal areas with clearly defined margins developed at the site of infarction. In the late phase (2 months onwards) growth was seen in the brain at the margins of the infarct in each case, and the size of the infarcted region showed a marked decrease in size. The rate of growth of the brain into the infarcted area exceeded that of the surrounding brain in some cases and was less in others. Growth of undamaged tissue may provide an important mechanism for recovery of the developing brain.

Brain↗

Chiari I malformation in asymptomatic young children with Williams syndrome: clinical and MRI study.

We report clinical and magnetic resonance imaging findings in two young children, aged 2 years 4 months and 3 years, with Williams syndrome. Both showed a mild global delay, although their neurological examination was completely normal. Their magnetic resonance imaging, however, showed Chiari I malformation and some non-specific changes in the centrum semiovale and in the white matter posterior to the lateral ventricles. Cerebellar tonsils were displaced through the foramen magnum 8.5 and 7.5 mm respectively. Our results suggest that Chiari I malformation can also be a frequent feature in subjects with Williams syndrome even in the absence of overt neurological signs suggestive of it. Whether these children might develop acute signs later is not known at present. Further studies are needed not only to evaluate the incidence of these findings in the global population of subjects with Williams syndrome but also to identify the children who are at risk for developing acute neurological signs.

Arnold-Chiari Malformation↗