Punctate White Matter Lesions Research Articles

On punctate white matter lesions in preterm infants: Is ultrasound diagnosis feasible?

ObjectivesTo observe hyperechoic nodular or punctate white matter lesions (HNPL) in a population of preterm infants using routine cranial ultrasound (cUS), to describe the characteristics of HNPL, and to compare them with punctate white matter lesions (PWML) detected in magnetic resonance imaging (MRI). DesignRetrospective observational single-center cohort study. SettingLevel 2B neonatal unit in France. Patients307 infants born <33 weeks gestation undergoing routine cUS with a total of 961 cUS performed. Main outcome measuresDescription of lesions (HNPL/PWML): presence or absence, number, size, location, and structural distribution. ResultsAmong the 307 included infants, 63 (20.5%) had at least one cerebral lesion, with 453 HNPL for 63 infants. HNPL were numerous (more than three in 66.6% of cases), primarily grouped in clusters (76.2%), located near the lateral ventricles (96.8%), and measuring more than 2 mm (79%). HNPL were diagnosed on day 29 on average and persisted until term. Overall, 43 MRI were performed in 307 infants, on average 18.9 days after last cUS, in 21 of those the indication was presence of HPNL on cUS. Of these 21 MRI, 14/21 presented 118 PWML compared to 173 HNPL on cUS. In the remaining MRI (7/21), no PWML were detected compared to 47 HNPL on cUS. ConclusionsIn our population of 307 preterm infants, cUS allowed the diagnosis of HNPL, with a large similarity to PWML in MRI and a better sensitivity. But in the absence of data on inter-observer variability, we cannot exclude overdiagnosis of HNPL.

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10years.

Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0weeks of gestation) and extremely preterm infants (EPT, < 28 + 0weeks of gestation) and across weeks of gestation. We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2weeks (SD 2 + 2weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. • Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning.

Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature

ObjectiveTo compare brain MRI biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). Study designWe examined 395 preterm infants (≤ 32 weeks gestational age[GA]) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III(BSID-III) at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. ResultsThe mean(SD) gestational age was 29.3(2.5) weeks; 35(8.9%) had POE and 20(5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs. 3.9%, respectively; p=0.002); findings remained significant with OR 4.16 (95% CI:1.26, 13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/GA (OR:0.93; 95% CI:0.78,1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95%CI: -11.8,-0.6) points on BSID-III Motor subscale compared with unexposed infants. ConclusionsPOE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.

O10 Multifocal congenital haemangiomas: expanding our understanding of “neonatal haemangiomatosis” – case series

Abstract Background Congenital haemangiomas are benign vascular tumours, typically solitary, categorised by their postnatal behaviour as rapidly involuting, non-involuting, or partially involuting. Histologically, they differ from infantile haemangiomas by the lack of immunostaining for GLUT-1. We present three infants with congenital, small, multifocal, non-progressive haemangiomas on the skin. Cases Our first patient was a male, born with 18 small vascular lesions. Abdominal ultrasound showed three vascular lesions in his liver and one in his left kidney, which were not visible on the repeated ultrasound in 3 months. MRI of the thorax showed a vascular lesion in the right hemithorax. He was completely asymptomatic, and the lung lesion was monitored annually with ultrasound. The second patient was a male, born with eight vascular lesions. He had an abdominal ultrasound, which was clear. He was also asymptomatic, and the lesions disappeared in the first year. The third patient was a female, born with 24 vascular lesions. Cranial ultrasound was clear; however, MRI head revealed nine punctate white matter lesions suggestive of vascular lesions. She had three small foci in the liver, consistent with haemangiomas, which were not detected after 6 weeks. All three patients had skin biopsy, which showed thin-walled dilated vessels in the dermis, negative for GLUT1 and D240. None of the patients had coagulopathy. Conclusion These three cases expand the diagnosis of congenital haemangioma to include a multifocal phenotype and demonstrate their possible association with visceral and intracranial lesions/abnormalities.

Automatic detection of punctate white matter lesions in infants using deep learning of composite images from two cases

Punctate white matter lesions (PWMLs) in infants may be related to neurodevelopmental outcomes based on the location or number of lesions. This study aimed to assess the automatic detectability of PWMLs in infants on deep learning using composite images created from several cases. To create the initial composite images, magnetic resonance (MR) images of two infants with the most PWMLs were used; their PWMLs were extracted and pasted onto MR images of infants without abnormality, creating many composite PWML images. Deep learning models based on a convolutional neural network, You Only Look Once v3 (YOLOv3), were constructed using the training set of 600, 1200, 2400, and 3600 composite images. As a result, a threshold of detection probability of 20% and 30% for all deep learning model sets yielded a relatively high sensitivity for automatic PWML detection (0.908–0.957). Although relatively high false-positive detections occurred with the lower threshold of detection probability, primarily, in the partial volume of the cerebral cortex (≥ 85.8%), those can be easily distinguished from the white matter lesions. Relatively highly sensitive automatic detection of PWMLs was achieved by creating composite images from two cases using deep learning.

CD8 Encephalitis in HIV: A Review of This Emerging Entity.

Encephalitis is a life-threatening neurological condition with multiple causes in the setting of Human Immunodeficiency Virus (HIV). CD8 Encephalitis (CD8E) is a newly recognised condition which can present in an acute manner, with pertinent features including classical radiological findings with an intense brain parenchymal infiltration of CD8+ T cells. This review attempted to clarify the symptomatology, distribution and determinants of this condition, as well as to examine its vast unknowns. A literature review was undertaken in July 2022, utilising the PubMed and Google Scholar databases. Papers published between 2006-2022 were reviewed. Eighteen papers, totalling 57 patients, were found and analysed. Statistical analysis was undertaken using Chi-squared and Wilcoxon rank-sum tests as appropriate, with p < 0.05 deemed significant. In this review, 57 patients were identified, with a female (61%, 34/56) and Black African (70%, 40/57) preponderance. Females were more likely to present with headache (p = 0.006), and headache was more likely to be present in those who died (p = 0.02). There was no statistically significant association between baseline CD4 count (p = 0.079) and viral load (p = 0.72) with disease outcome. Overall, 77% (41/53) of patients had classical imaging findings, including bilateral gadolinium-enhancing punctate and perivascular white matter lesions. However, many patients (23/57) required a brain biopsy as part of their diagnostic workup. Corticosteroid treatment was commonly prescribed in patients (64%, 35/55) and had a mortality benefit, with an overall survival in this group of 71% (p = 0.0008). In those who died, median survival was 5.5 months. In rare instances, recurrence of the disease was noted, which responded poorly to treatment. CD8E represents a new and complex condition with few risk factors identified for its occurrence. The presenting symptoms are broad, but headache appears to be more common in females and more significantly associated with death. Though rare, CD8E is likely under-diagnosed, possibly due to overlapping features with other illnesses and lack of physician experience in its recognition and management. Corticosteroids demonstrate a clear mortality benefit, but more studies are required to determine their optimal dosing and duration, as well as the use of steroid-sparing agents. Further reviews should help to better determine the risk factors for the condition, as well as non-invasive biomarkers, to aid in diagnosis and help to predict poor prognosis and disease recurrence.

Comparison of the Clinical Characteristics of Infants with Punctate White Matter Lesions and/or Cystic Lesions

We aimed to investigate the differences in the clinical characteristics of preterm infants with punctate white matter lesions (PWMLs) and those with cystic periventricular leukomalacia (cPVL) using term-equivalent age magnetic resonance imaging. We conducted a retrospective case-control study to explore the clinical characteristics of infants (< 35 weeks gestation, born between 2007 and 2017 in a single Level III perinatal center) with PWML, cPVL or with PWML plus cPVL and compared them with those of gestational-age-matched controls. Among 602 infants, 29, 5, and 4 were assigned to the PWML group, cPVL group, and PWML plus cPVL group (PWML-cPVL group), respectively. Compared to the control group (n = 87), the PWML group had higher birth weights (p = 0.04), rates of histological chorioamnionitis (p = 0.04), vaginal delivery (p = 0.008), and early heart contraction failure (within 72 hours after birth) (p = 0.003). The cPVL group had lower umbilical blood gas base excess (p = 0.01), higher rate of late-onset circulatory collapse (p = 0.008), and higher hydrocortisone requirements (p = 0.03) than the control group (n = 15). The PWML-cPVL group had a higher rate of intraventricular hemorrhage (p = 0.03) than the control group (n = 12). In the multivariate logistic regression analysis, vaginal delivery (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.37-9.40; p = 0.009), higher birth weight (per 1 g) (OR = 1.001; 95% CI = 1.0001-1.002; p = 0.03), and early heart contraction failure (OR = 5.4; 95% CI = 1.84-16.8; p = 0.002), were independent risk factors for PWML. Clinical characteristics of infants with PWML compared with gestational-age-matched controls differed from those with cPVL or PWML plus cPVL, as PWML were not related to severe disruption of hemodynamics.

Evaluation of the Prevalence of Punctate White Matter Lesions in a Healthy Volunteer Neonatal Population.

Hypoxic-ischemic injury is the most common cause of neonatal encephalopathy. T1-weighted punctate white matter lesions have been described in hypoxic-ischemic injury. We have reviewed a healthy volunteer neonatal population to assess the prevalence of punctate white matter lesions in neonates with no clinical signs of hypoxic-ischemic injury. Fifty-two subjects were scanned on a neonatal-specific 3T MR imaging scanner. Twelve patients were excluded due to the lack of T1-weighted imaging, leaving a total of 40 patients (35 term, 5 preterm) assessed in the study. One had a solitary T1-punctate white matter lesion. We concluded that solitary punctate white matter lesions have a low prevalence in healthy neonates.

Incidental findings on brain MR imaging of asymptomatic term neonates in the Developing Human Connectome Project.

BackgroundInterpretation of incidental findings on term neonatal MRI brain imaging can be challenging as there is a paucity of published normative data on asymptomatic term neonates. Reporting radiologists and clinicians need to be familiar with these incidental findings to avoid over-investigation and misinterpretation particularly in relation to neurodevelopmental outcome. This study aimed to determine the prevalence of incidental findings in a large group of asymptomatic term neonates participating in the Developing Human Connectome Project (dHCP) who were invited for neurodevelopmental assessment at 18 months.MethodsWe retrospectively reviewed MRI brain scans performed on 500 term neonates enrolled in the dHCP study between 2015 and 2019 with normal clinical examination. We reviewed the results of the Bayley Scales of Infant and Toddler Development (Bayley III) applied to participants who attended for neurodevelopmental follow-up at 18 months. Scores considered “delayed” if <70 on language, cognitive or motor scales.FindingsIncidental findings were observed in 47% of term infants. Acute cerebral infarcts were incidentally noted in five neonates (1%). More common incidental findings included punctate white matter lesions (PWMLs) (12%) and caudothalamic subependymal cysts (10%). The most frequent incidental finding was intracranial haemorrhage (25%), particularly subdural haemorrhage (SDH). SDH and PWMLs were more common in infants delivered with ventouse-assistance versus other delivery methods.Neurodevelopmental results were available on 386/500 (77%). 14 infants had a language score < 70 (2 SD below the mean). Of the 386 infants with neurodevelopmental follow up at 18 months, group differences in motor and language scores between infants with and without incidental findings were not significant (p = 0·17 and p = 0·97 respectively). Group differences in cognitive scores at 18 months between infants with (median (interquartile range) -100 (95–105)) and without (100 (95–110)) incidental findings were of small effect size to suggest clinical significance (Cliff's d = 0·15; p<0·05).InterpretationIncidental findings are relatively common on brain MRI in asymptomatic term neonates, majority are clinically insignificant with normal neurodevelopment at 18 months.FundingThis work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/20072013/ERC grant agreement no. [319456] dHCP project), by core funding from the Wellcome/EPSRC Centre for Medical Engineering [WT203148/Z/16/Z] and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

Serial magnetic resonance imaging changes of pseudotumor lesions in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a case report

BackgroundRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an adult-onset rare monogenic microvasculopathy. Its typical neuroimaging features are punctate white matter lesions or pseudotumor alterations. RVCL-S is often under-recognized and misdiagnosed because of its rarity and similar imaging manifestations to multiple sclerosis or brain malignant mass.Case presentationHere we report a case of a 36-year-old Chinese man who developed multiple tumefactive brain lesions spanning over two years leading to motor aphasia, cognitive decline, and limb weakness. He also presented with slight vision loss, and fundus fluorescein angiography indicated retinal vasculopathy. He underwent brain biopsies twice and showed no evidence of malignancy. Given the family history that his father died of a brain mass of unclear etiology, RVCL-S was suspected, and genetic analysis confirmed the diagnosis with a heterozygous insertion mutation in the three-prime repair exonuclease 1 gene. He was given courses of corticosteroids and cyclophosphamide but received little response.ConclusionsThe present case is one of the few published reports of RVCL-S with two-year detailed imaging data. Serial magnetic resonance images showed the progression pattern of the lesions. Our experience emphasizes that a better understanding of RVCL-S and considering it as a differential diagnosis in patients with tumefactive brain lesions may help avoid unnecessary invasive examinations and make an earlier diagnosis.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI–) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI– PWMLs.Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database.Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively).Conclusions: Our results suggest a nosological difference between SWI+ and SWI– PWMLs. Other prospective studies are warranted to corroborate these observations.

Risk Factors for Hydrocephalus in Neonatal Purulent Meningitis: A Single-Center Retrospective Analysis.

Hydrocephalus is a potentially lethal complication of neonatal purulent meningitis. Early detection of hydrocephalus helps to determine optimal treatment, improve prognosis, and reduce financial burden. We aimed to analyze the risk factors for hydrocephalus in neonates with purulent meningitis and discuss the characteristics of the disease. The records of neonatal purulent meningitis admitted to the Children Hospital of Fudan University from January 2013 to September 2019 were retrospectively included in the study cohort. The data of clinical, laboratory, and cranial magnetic resonance images (MRIs) were collected and analyzed (except discharge data) by univariate analysis, and P values <.05 were further analyzed by multivariate logistic regression. A total of 197 children who met the inclusion criteria were enrolled in the study cohort. Overall, 39.6% (78/197) of the patients had positive pathogen cultures, and 60.4% (119/197) of patients had clinical diagnosis of meningitis with negative pathogen cultures. Among 197 children, 67 of them experienced hydrocephalus, and the factors that were significantly associated with hydrocephalus in multivariate analysis were female sex, cerebrospinal fluid glucose <2 mmol/L, periventricular leukomalacia, punctate white matter lesions, and pyogenic intraventricular empyema. Children with hydrocephalus had a lower cure rate of meningitis (31.3% vs 75.4%), and poor discharge outcomes. In addition, they had longer length of hospital stay and higher hospital cost. Female sex, cerebrospinal fluid glucose <2 mmol/L, periventricular leukomalacia, punctate white matter lesions, and pyogenic intraventricular empyema were identified as risk factors for hydrocephalus in neonatal purulent meningitis. Children with hydrocephalus had poor discharge outcomes and increased financial burden on their families.

Incidence of brain lesions in moderate-late preterm infants assessed by cranial ultrasound and MRI: The BIMP-study

PurposeTo evaluate the incidence and characteristics of brain lesions in moderate-late preterm (MLPT) infants, born at 32–36 weeks’ gestation using cranial ultrasound (cUS) and magnetic resonance imaging (MRI). MethodsProspective cohort study carried out at Isala Women and Children’s Hospital between August 2017 and November 2019. cUS was performed at postnatal day 3–4 (early-cUS), before discharge and repeated at term equivalent age (TEA) in MLPT infants born between 32+0 and 35+6 weeks’ gestation. At TEA, MRI was also performed. Several brain lesions were assessed e.g. hemorrhages, white matter and deep gray matter injury. Brain maturation was visually evaluated. Lesions were classified as mild or moderate-severe. Incidences and confidence intervals were calculated. Results166 MLPT infants were included of whom 127 underwent MRI. One or more mild lesions were present in 119/166 (71.7 %) and moderate-severe lesions in 6/166 (3.6 %) infants on cUS and/or MRI. The most frequent lesions were signs suggestive of white matter injury: inhomogeneous echogenicity in 50/164 infants (30.5 %) at early-cUS, in 12/148 infants (8.1 %) at TEA-cUS and diffuse white matter signal changes (MRI) in 27/127 (23.5 %) infants. Cerebellar hemorrhage (MRI) was observed in 16/127 infants (12.6 %). Delayed maturation (MRI) was seen in 17/117 (13.4 %) infants. Small hemorrhages and punctate white matter lesions were more frequently detected on MRI than on cUS. ConclusionsIn MLPT infants mild brain lesions were frequently encountered, especially signs suggestive of white matter injury and small hemorrhages. Moderate-severe lesions were less frequently seen.

Diagnostic Specificity of Cerebral Magnetic Resonance Imaging for Punctate White Matter Lesion Assessment in a Preterm Sheep Fetus Model.

Recent studies, using magnetic resonance imaging (MRI) to assess white matter injury in preterm brains, increasingly recognize punctate white matter lesions (PWML) as the primary lesion type. There are some papers showing the relationship between the size and number of PWML and the prognosis of infants. However, the histopathological features are still unknown. In this study, we experimentally induced periventricular leukomalacia (PVL) in a sheep fetus model, aiming to find whether MRI can visualize necrotic foci (small incipient lesions of PVL) as PWML. Three antenatal insults were employed to induce PVL in preterm fetuses at gestational day 101-117: (i) hypoxia under intrauterine inflammation, (ii) restriction of artificial placental blood flow, and (iii) restriction of artificial placental blood flow after exposure to intrauterine inflammation. MRI was performed 3-5days after the insults, and standard histological studies of the PVL validated its findings. Of the 89 necrotic foci detected in histological samples from nine fetuses with PVL, 78 were visualized as PWML. Four of the lesions detected as abnormal findings on MRI could not be histologically detected as corresponding abnormal findings. The diagnostic sensitivity and positive predictive values of histologic focal necrosis visualized as PWML were 0.92 and 0.95, respectively. The four lesions were excluded from these analyses. These data suggest that MRI can visualize PVL necrotic foci as PWML 3-5days after the injury induction. PWML can spontaneously become obscure with time after birth, so their accurate diagnosis in the acute phase can prevent overlooking mild PVL.

MRI Findings at Term-Corrected Age and Neurodevelopmental Outcomes in a Large Cohort of Very Preterm Infants.

Brain MR imaging at term-equivalent age is a useful tool to define brain injury in preterm infants. We report pragmatic clinical radiological assessment of images from a large unselected cohort of preterm infants imaged at term and document the spectrum and frequency of acquired brain lesions and their relation to outcomes at 20 months. Infants born at <33 weeks' gestation were recruited from South and North West London neonatal units and imaged in a single center at 3T at term-equivalent age. At 20 months' corrected age, they were invited for neurodevelopmental assessment. The frequency of acquired brain lesions and the sensitivity, specificity, and negative and positive predictive values for motor, cognitive, and language outcomes were calculated, and corpus callosal thinning and ventricular dilation were qualitatively assessed. Five hundred four infants underwent 3T MR imaging at term-equivalent age; 477 attended for assessment. Seventy-six percent of infants had acquired lesions, which included periventricular leukomalacia, hemorrhagic parenchymal infarction, germinal matrix-intraventricular hemorrhage, punctate white matter lesions, cerebellar hemorrhage, and subependymal cysts. All infants with periventricular leukomalacia, and 60% of those with hemorrhagic parenchymal infarction had abnormal motor outcomes. Routine 3T MR imaging of the brain at term-equivalent age in an unselected preterm population that demonstrates no focal lesion is 45% sensitive and 61% specific for normal neurodevelopment at 20 months and 17% sensitive and 94% specific for a normal motor outcome. Acquired brain lesions are common in preterm infants routinely imaged at term-equivalent age, but not all predict an adverse neurodevelopmental outcome.

Modelling brain development to detect white matter injury in term and preterm born neonates.

Premature birth occurs during a period of rapid brain growth. In this context, interpreting clinical neuroimaging can be complicated by the typical changes in brain contrast, size and gyrification occurring in the background to any pathology. To model and describe this evolving background in brain shape and contrast, we used a Bayesian regression technique, Gaussian process regression, adapted to multiple correlated outputs. Using MRI, we simultaneously estimated brain tissue intensity on T1- and T2-weighted scans as well as local tissue shape in a large cohort of 408 neonates scanned cross-sectionally across the perinatal period. The resulting model provided a continuous estimate of brain shape and intensity, appropriate to age at scan, degree of prematurity and sex. Next, we investigated the clinical utility of this model to detect focal white matter injury. In individual neonates, we calculated deviations of a neonate's observed MRI from that predicted by the model to detect punctate white matter lesions with very good accuracy (area under the curve > 0.95). To investigate longitudinal consistency of the model, we calculated model deviations in 46 neonates who were scanned on a second occasion. These infants' voxelwise deviations from the model could be used to identify them from the other 408 images in 83% (T2-weighted) and 76% (T1-weighted) of cases, indicating an anatomical fingerprint. Our approach provides accurate estimates of non-linear changes in brain tissue intensity and shape with clear potential for radiological use.

White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposue

Previous studies have not found structural injury or brain malformations in infants and children with prenatal opioid exposure. As part of an ongoing study evaluating neuroimaging in infants with prenatal opioid exposure, we reviewed structural brain MR imaging in 20 term infants with prenatal opioid exposure and 20 term controls at 4-8 weeks of age. We found that 8 of the 20 opioid-exposed infants had punctate white matter lesions or white matter signal abnormality on structural MR imaging, and 2 of the opioid-exposed infants had a septopreoptic fusion anomaly. No controls had white matter injury or structural malformations. Our findings underscore the importance of clinical neurodevelopmental follow-up and the need for more comprehensive imaging and long-term outcomes research following prenatal opioid exposure.

Detection of occult abnormalities in the deep gray matter nuclei of neonates with punctate white matter lesions by magnetic resonance spectroscopy.

Punctate white matter lesions (PWML) are common in preterm neonates and have also been reported in the full term. While most studies focus on white matter abnormalities, gray matter (GM) alterations are generally ignored due to thelack of abnormalities on conventional MRI. This study aims to investigate whether magnetic resonance spectroscopy is a sensitive and practical method to detect occult alterations of deep GM nuclei in these neonates. Neonates with PWML and controls with no MRI abnormalities were retrospectively studied. Apparent diffusion coefficient values and metabolic ratios (Cho/Cr, NAA/Cho, and NAA/Cr) in the lenticular nucleus and the thalamus were compared between the PWML and control groups. Forty-two neonates with PWML (grades I, II, and III contained 14, 21, and 7 subjects, respectively) and 50 controls were enrolled. Apparent diffusion coefficient values in the lenticular nucleus and the thalamus were not significantly different between the PWML and the control groups. The NAA/Cho ratio was significantly lower in the PWML group than in the control group in both regions, whereas a lower NAA/Cr ratio was only observed in the thalamus. Significantly lower ratios of NAA/Cho in both regions and NAA/Cr in the thalamus were detected in the grade II and III subgroup, whereas the thalamic NAA/Cho ratio was decreased in the grade I group compared with controls. Magnetic resonance spectroscopy is a sensitive method for detecting the occult deep GM abnormalities for the study cohort of neonates with PWML when compared with subjects without PWML.

Punctate white matter lesions of preterm infants: Risk factor analysis.

Punctate white matter lesions (PWML) are frequently detected in preterm infants undergoing brain MRI at term equivalent age (TEA). The aims of this study were to assess prevalence of PWML and to identify risk factors for PWML in VLBW infants. Brain MRI scans obtained at TEA and clinical charts of a consecutive sample of very low birth weight (VLBW) infants admitted to Gaslini Children's Hospital NICU between 2012 and 2016 were retrospectively analyzed. MRI protocol included Susceptibility Weighted Imaging (SWI) sequence in order to identify hemosiderin depositions as a result of previous microbleeds. PWML were classified according to their number (≤6 lesions and >6 lesions) and signal characteristics (SWI+ lesions and SWI- lesions). Univariate and multivariable analysis were performed in order to identify risk factors for PWML (as a whole) and for each subgroup of PWML. 321 VLBW infants were included. PWML were identified in 61 subjects (19%), 26 of whom (8% of the study population) had more than 6 lesions. Risk factors for PWML (as a whole) were higher birth weight (OR=1.001; p=0.04) and absent or incomplete antenatal steroid course (OR=2.13; p=0.02). Risk factors for >6PWML were need for intubation (OR=11.9; p=0.003) and higher Apgar score at 5min (OR=1.8; p=0.02). Presence of GMH-IVH was the only identified risk factor for SWI+lesions. Our results confirm the high prevalence of PWML among VLBW infants. Differentiation between SWI+ and SWI- lesions is crucial as they have different risk factors and may likely represent two different entities.